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For a PDF of the 2015 Program Materials <click here>
For ALL Abstracts [1-220] in sequential order <click here>
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Sunday, August 23
 

5:00pm

Conference Registration
Register for the conference and get your tote bag, and name badge (color coded to identify ISHC members).   Registration at the Corwin Pavilion Lobby is also possible on Monday through Friday from 8:30 am - 5:00pm, until the conference is over, excepting noon-5:00pm on Wednesday.

For those staying on-campus, please see the Manzanita front desk (DeAnza Building) for your room keys and long-term parking permit for 22 Structure.

Map to South Coast Inn and area attractions. 



Sunday August 23, 2015 5:00pm - 7:30pm
Corwin Pavilion

5:30pm

Reception
Limited Capacity seats available

Reception with Domestic & International Cheeses with Fruit & Crackers, Assorted Sodas & Bottled Waters, Red & White Wines, Imported and Domestic Bottled Beer.    

Should participants wish to have something more substantial Ortega Dining Hall will be open and dinner can be purchased for $12.   In addition, there are several dining establishments in Isla Vista, off of Madrid Road within walking distance.  Consult the maps under venues.


Sunday August 23, 2015 5:30pm - 7:30pm
UCEN Lagoon Plaza

7:00pm

Dinner

Dinner in Ortega on Sunday is included in the board package ONLY for those staying in Manzanita.  Otherwise, pay $12 at the door.  For those not staying on campus, there are many places to eat in Isla Vista, the neighboring community.

Isla Vista Eateries 

 


Sunday August 23, 2015 7:00pm - 8:00pm
Ortega Dining Commons
 
Monday, August 24
 

7:30am

Breakfast
Monday August 24, 2015 7:30am - 8:30am
Ortega Dining Commons

8:40am

Announcements
Opening Announcements

Monday August 24, 2015 8:40am - 9:00am
Corwin Pavilion

9:00am

[0200] Enantioselective Synthesis of Heterocycles from Carbon-Carbon Multiple Bonds
Limited Capacity seats available

This lecture will emphasize a reactivity driven approach to development of electrophilic catalysts for addition, rearrangement, cycloaddition and coupling reactions of C-C multiple bonds. More specifically, the application of cationic gold(I) complexes, chiral counterions and chiral acids. in enantioselective transformations initiated by π-activation will be discussed. Particular attention will be devoted to the mechanistic hypotheses that form the basis for catalyst discovery and the development of new reactions.

Plenaries and Awardees
avatar for F. Dean Toste

F. Dean Toste

Professor of Chemistry, University of California, Berkeley
Dean was born in 1971 in Tercelra, Azores, Portugal, but soon moved to Canada. While at the University of Toronto, he majored in Chemistry and Biochemistry and went on to obtain a M.Sc. in Organic Chemistry. He then pursued his Ph.D. with Barry Trost at Stanford and a post-doctoral appointment with Robert Grubbs at Caltech. Dean is currently a Professor of Chemistry at UC Berkeley.



Monday August 24, 2015 9:00am - 10:00am
Corwin Pavilion

10:00am

Coffee Break
Monday August 24, 2015 10:00am - 10:20am
UCEN Lagoon Plaza

10:20am

[0215] The Functionalization of C—H Bonds
Limited Capacity seats available

Among the frontier challenges in chemistry in the 21st century are the interconnected goals of increasing control of chemical reactivity while synthesizing and diversifying complex molecules with higher efficiency. Traditional organic methods for installing oxidized functionality rely heavily on acid-base reactions that require extensive functional group manipulations (FGMs). In contrast, nature routinely uses allylic and aliphatic C—H oxidation methods, generally mediated by heme and non-heme iron monooxygenase enzymes, to directly install oxidized functionality into the preformed hydrocarbon framework of complex molecules. Due to their ubiquity in complex molecules and inertness to most organic transformations, C—H bonds have typically been ignored in the context of methods development for total synthesis. The exceptions to this rely on substrate directing groups to facilitate site-selectivity and reactivity. The discovery and development of highly selective oxidation methods for the direct installation of oxygen, nitrogen and carbon into allylic and aliphatic C—H bonds of complex molecules and their intermediates are discussed.  Unlike Nature which uses elaborate shape or functional group recognition active sites, this chemistry harnesses the subtle electronic, steric, and stereoelectronic interactions between C—H bonds and small molecule transition metal complexes to achieve high regio-, chemo-, stereo- and site-selectivities with high substrate generality- and without the requirement for directing groups. Our current understanding of these interactions gained through empirical and mechanistic studies will be discussed. A user-friendly catalyst reactivity model that calculates and even predicts the major site of oxidation as well as the magnitude and direction of the site-selectivity in complex substrates as a function of catalyst will be delineated. Novel strategies for streamlining the process of complex molecule synthesis and diversification enabled by these methods will be presented. 


Plenaries and Awardees
avatar for M Christina White

M Christina White

Professor of Chemistry, University of Illinois
Professor M. Christina White received her B.A. with highest honors in Biochemistry from Smith College in 1992 and her Ph.D. from Johns Hopkins University in 1998. After a postdoctoral fellowship at Harvard University, she joined the faculty there in 2002. In 2005 she joined the faculty at the University of Illinois at Urbana-Champaign. Her research interests are in the field of organic synthesis with an emphasis on the discovery of... Read More →



Monday August 24, 2015 10:20am - 11:20am
Corwin Pavilion

11:20am

[0167] Application of C-H Functionalization Reactions to the Synthesis of Novel Heterocycles
Limited Capacity seats available

In the first part of the lecture, a two-step synthesis of structurally diverse 3-aminoindazoles from readily available starting materials will be presented. This sequence includes a one-pot chemoselective electrophilic activation of tertiary amides and nucleophilic addition of hydrazides to form aminohydrazones. These precursors then participate in an intramolecular ligand-free Pd-catalyzed C-H amination. The azaheterocycles synthesized via this approach were further diversified by subsequent deprotection/functionalization and transition Ru-catalyzed C-H arylation. 

In the second part of the presentation, the preparation of tailored novel fluorescent derivatives that features an intramolecular C-H functionalization will be presented. The fluorescent properties can easily be fined tuned by modifying the basic molecular scaffold

Plenaries and Awardees
avatar for André B. Charette

André B. Charette

Professor, Université de Montréal
Born in 1961 in Montréal, André B. Charette received his B.Sc. in 1983 from the Université de Montréal. He then moved south of the border to the University of Rochester to continue his graduate studies. Under the supervision of Robert K. Boeckman Jr., he completed the total synthesis of the ionophore calcimycin, which earned him the degrees of M.Sc. (1985) and Ph.D. (1987). Following an NSERC postdoctoral fellowship at... Read More →



Monday August 24, 2015 11:20am - 12:20pm
Corwin Pavilion

12:30pm

Lunch
Monday August 24, 2015 12:30pm - 1:45pm
Ortega Dining Commons

2:00pm

[0083] Enantioselective N-heterocyclic Carbene Catalysis with Ester Substrates
Limited Capacity seats available

N-Heterocyclic carbenes (NHCs) are powerful catalysts for some of the most diverse chemical transformations observed in organocatalysis.1 Beyond acyl anion chemistry they are active in many reactions that are acyl anion free often exploiting normal polarity intermediates.2 A number of our studies in the field of NHC catalysis are focused on reaction discovery using ester, and ester surrogate, substrates. In this presentation recent discoveries in enantioselective catalysis using Lewis basic, and nucleophilic, catalysts will be discussed


Invited Lecturers
avatar for David Lupton

David Lupton

Associate Professor, Monash University


Monday August 24, 2015 2:00pm - 2:40pm
UCEN Flying A

2:00pm

[0202] Development of New Higher-Order Carbocyclization Reactions: Emulating Terpene Biosynthesis
Limited Capacity seats available

Transition metal-catalyzed higher-order carbocyclization reactions provide powerful methods for the stereoselective construction of complex polycyclic systems that are generally not accessible via classical pericyclic reactions.[1]  We have demonstrated the merit of the rhodium-catalyzed [m+n+n] carbocyclization reactions of carbon and heteroatom tethered 1,6-enynes with carbon monoxide, alkynes and dienes.  More recently we have explored the development of a stereoselective rhodium-catalyzed [3+2+2] carbocyclization of 1,6-alkenylidenecyclopropanes with activated alkynes for the construction of cis-fused bicycloheptadienes,[2] which prompted the isolation of the key metallacycle intermediate[3] and the expansion of the scope of p-fragments to carbon monoxide and allenes.[4,5]  The seminar will outline some of these developments and their application to challenging bioactive natural products.

References

1.  Inglesby, P. A.; Evans, P. A. Chem. Soc. Rev. 2010, 39, 2791.

2.  (a) Evans, P. A.; Inglesby, P. A. J. Am. Chem. Soc. 2008, 130, 12838.  (b) Evans, P. A.; Inglesby, P. A.; Kilbride, K. Org. Lett. 2013, 15, 1798.  (c) Evans, P. A.; Negru, D. E.; Shang, D. Angew. Chem. Int. Ed. 2015, 54, 4768.

3.  Inglesby, P. A.; Bacsa, J.; Negru, D. E.; Evans, P. A. Angew. Chem. Int. Ed. 2014, 53, 3952.

4.  Mazumder, S.; Shang, D.; Negru, D. E.; Baik, M.-H.; Evans, P. A. J. Am. Chem. Soc. 2012, 134, 20569.

Invited Lecturers
avatar for P. Andrew Evans

P. Andrew Evans

Professor and Alfred R. Bader Chair of Organic Chemistry, Queen's University


Monday August 24, 2015 2:00pm - 2:40pm
Corwin West

2:00pm

[0203] Novel Strategies for the Preparation of Functionalizable Heterocyclic Motifs
Limited Capacity seats available

The preparation of heterocyclic motifs provides an exciting platform from which to conduct fundamental research, particularly that which supports the study of the interaction of small molecules with therapeutically-relevant biological targets. Densely packed arrangements of heteroatoms and stereogenic centers constituting these polycyclic subunit challenge the limits of current technology, prompting the need for new strategies for the synthesis of these systems. Novel approaches which have demonstrated our access to these challenging molecular architectures will be presented-- a ruthenium-catalyzed hydrogen transfer of 1,3-diols in the presence of alkyl hydrazines to furnish 1,4-disubstituted pyrazoles and an intramolecular displacement of an a-carbonyl fluoride by a tethered alkoxide to furnish [2.2.1] azabicyclics with excellent stereocontrol will be disseminated. Furthermore, a versatile approach to 5,6-fused heteroaromatics will be described which involves the conjugate addition of a metallated 2-fluoropyridine to substituted nitroolefins followed by a tractable 3-step sequence capable of furnishing these highly important bicyclic arrays.  


Invited Lecturers
avatar for Andrew Flick

Andrew Flick

Principal Scientist, Pfizer
Synthesis Lab HeadPfizer | May 2011 – Present (3 years 10 months) | | Senior ScientistPfizer | May 2008 – May 2011 (3 years 1 month)groton, ct | Neurosciences discovery chemistry, inflammation/immunology discovery chemistry | | Research AssociateArray BioPharma | February 2001 – August 2003 (2 years 7 months)Longmont | Organic synthesis | | Product SpecialistAbbott | May... Read More →


Monday August 24, 2015 2:00pm - 2:40pm
MCC Theater

2:00pm

[0205] Nitrogen Dense Heterocycles as Antibiotic Adjuvants
Limited Capacity seats available

The emergence of resistance to multiple antimicrobial agents in pathogenic bacteria has become a significant global public health threat. Drug resistant bacterial infections cause considerable patient mortality and morbidity, and rising antibiotic resistance is seriously threatening the vast medical advancements made possible by antibiotics over the past 70 years. The Centers for Disease Control and Prevention (CDC) estimates that over two million people acquire antibiotic resistant bacterial infections each year in the United States, and more than 23,000 people die as a result.

While the development of new antibiotics is one approach for the treatment of multi drug resistant pathogens, the fact remains that bacteria invariably develop resistance to any introduced therapy that relies solely upon a single bacteriostatic/bactericidal mechanism.  For example, daptomycin was introduced into the clinic in 2003, and less than a year later the emergence of resistance was observed. As a result, alternative approaches to controlling bacterial infections are sorely needed and underexploited. Once such approach is the identification of genes and pathways that play an important role in bacterial resistance to currently approved antibiotics, and the identification of small molecule adjuvants that target and block these pathways, thereby repotentiating the activity of the antibiotic when administered as a combination therapy. Efforts in our lab towards the development of such adjuvants based upon functionalized 2-aminoimidazoles will be presented, focusing on examples of breaking antibiotic resistance in multidrug resistant Gram-negative pathogens.

Invited Lecturers
avatar for Christian Melander

Christian Melander

Howard Schaeffer Distinguished Professor, NC State University
Background Postdoctoral, The Scripps Research Institute, 2002 - 2004 Lead Scientist, Xencor, 2001-2002 Postdoctoral, California Institute of Technology,1998 - 2001 Ph. D., Organic Chemistry, Columbia University, 1998 M. Phil., Organic Chemistry, Columbia University, 1998 M. A., Organic Chemistry, Columbia University, 1995 B. S., Chemistry, University of California, Davis, 1994 Awards NIH Postdoctoral Fellowship... Read More →


Monday August 24, 2015 2:00pm - 2:40pm
Corwin East

2:40pm

[0057] Enantioselective Organocatalytic Cycloadditions via Hydrogen Bond Catalysis
Limited Capacity seats available

Asymmetric Brønsted acid catalysis has rapidly emerged as a powerful strategy for the synthesis of chiral, biologically relevant compounds, complementing enzymes and metal complexes. For the past five years we have been interested in developing enantioselective cycloadditions catalyzed by chiral Brønsted acid catalysts.

This talk will present our work in this area, which includes the asymmetric cycloaddition syntheses of various six- and five-membered nitrogen-containing heterocyles.2 We also applied these methodologies in the synthesis of biologically active natural and non-natural products.


Invited Lecturers
avatar for Geraldine Masson

Geraldine Masson

Professor, Institut de Chimie des Substances
SHORT BIOGRAPHY 2014: Research Director DR2 - Section 12 - Institute of Chemistry of Natural Substances, INSC-CNRS, Gif-sur-Yvette. 2009: Researcher CR1 - Section 12 - Institute of Natural Substances Chemistry INSC-CNRS, Gif-sur-Yvette.  | - 2010 Habilitation Research , University Paris-Sud XI, Orsay. 2005: Research Fellow CR2 - Section 12 - Prof. team Jieping Zhu, Institute of Natural Substances... Read More →


Monday August 24, 2015 2:40pm - 3:20pm
UCEN Flying A

2:40pm

[0076] To Phlegmarines and Beyond - Strategies for Efficiency and Diversity in Natural Product Synthesis
Limited Capacity seats available

The Lycopodium alkaloids have attracted enormous attention in recent years for their medicinal properties as well as the synthetic challenges they present.1  

We have used the stereochemically diverse phlegmarine group as a platform to develop new synthetic methods including the use of organocatalysis,2 tandem reactions and stereocontrolled reductions based on radical, homogeneous and directed heterogeneous catalysis. The use of these methods in conjunction with solid supported reagents and pot economy strategies have allowed for easy gram scale synthesis of these compounds in a single flask.3  This presentation will give an overview of this work and illustrate the potential of the underlying strategies to access all of the other Lycopodium alkaloids, their analogs as well as a diverse portfolio of other important heterocyclic nuclei.


Invited Lecturers
avatar for Ben Bradshaw

Ben Bradshaw

Associate Professor, University de Barcelona
Obtained Ph.D Thesis from the University of Manchester, England (1996-2000) under supervision of Professor J. A Joule on the total synthesis of the Molybdenum CoFactor. After working for a start up company also based at the university of Manchester and a brief postdoctoral position on the total synthesis of the bryostatins (Professor E.J Thomas Group) he moved to the Pharmacy Department at the University of Barcelona in 2004 as a postdoctoral... Read More →


Monday August 24, 2015 2:40pm - 3:20pm
Corwin West

2:40pm

[0132] Can Ketones Be Productive Dienophiles For IEDDA Reactions?
Limited Capacity seats available

The development of the inverse electron demand Diels-Alder (IEDDA) reactions of 1,3,5-triazines has led to the total syntheses of a series of pyrimidine-containing natural products and the preparation of highly functionalized pyrimidine heterocycles.1 The dienophiles of these IEDDA reactions have been limited to electron-rich alkenes and alkynes, such as enamines, ynamines and amidines. Recently, we have discovered that ketones could be employed directly as productive dienophiles in the 1,3,5-triazine IEDDA reactions under conditions, such as using catalytic amount of hydrazine and trifluoroacetic acid. For examples, pyrimidine fused heterocycle 1 and functionalized pyridine-4-amine 2 may be prepared in moderate to excellent yields by applications of the new methods. The details of these investigations will be discussed.


Invited Lecturers
avatar for Xu Bai

Xu Bai

Chief Executive Officer and President, Changchun Discovery Sciences, Ltd.
Bai Xu, Ph.D. founded Changchun Discovery Sciences, Ltd. and serves as its Chief Executive Officer and President. Dr. Xu served as a Group Leader and Lead Chemist in the Advanced Technology Division and Leader of the Cardiovascular Project at CombiChem, Inc. He served as Research Scientist, Senior Scientist and Lead Chemist of the Internal Project (with emphasis on cardiovascular disease and organ protection) at IDUN Pharmaceuticals. Dr. Xu... Read More →


Monday August 24, 2015 2:40pm - 3:20pm
MCC Theater

2:40pm

[0199] Total Synthesis of Periploside A, a unique Pregnane Hexasaccharide with Potent Immunosuppressive Effects
Limited Capacity seats available

Periploside A is a pregnane hexasaccharide identified from the Chinese medicinal plant Periploca sepium, which features a unique seven-membered formyl acetal bridged orthoester (FABO) motif and shows potent immunosuppressive activities. The total synthesis of this natural product is achieved in a total of 76 steps with the longest linear sequence of 29 steps and 9.2% overall yield.[1] The FABO motif is constructed via a combination of Sinaÿ’s and Crich’s protocol for the formation of orthoester and acetal glycosides, respectively. The 2-deoxy-b-glycosidic linkages are assembled stereoselectively with judicious choice of the glycosylation methods.[2,3] The epimer at the spiro-quaternary carbon in the FABO motif has also been elaborated in a stereo-controlled manner. This epimer, as well as the synthetic analogs bearing FABO motif, retain largely the inhibitory activities of periploside A against the proliferation of T-lymphocyte, indicating the importance of the chemical connection of the FABO motif to their immunosuppressive activities.


Invited Lecturers
avatar for Biao Yu

Biao Yu

Professor, Shanghai Institute of Organic Chemistry
Shanghai Institute of Organic Chemistry, Chinese Academy of fellow  | PI, Shanghai Institute of Organic Chemistry (SIOC), Chinese Academy of Sciences (CAS) , director of the State Key Laboratory of Organic Chemistry, Director, State Key Laboratory of Bioorganic and Natural Products ChemistryShanghai Institute of Organic Chemistry deputy director of Institute Deputy Director, SIOC, CAS


Monday August 24, 2015 2:40pm - 3:20pm
Corwin East

3:20pm

Coffee Break
Monday August 24, 2015 3:20pm - 3:40pm
UCEN Lagoon Plaza

3:40pm

[0015] Synthetic Studies Towards Spiroindimicins B-D
Limited Capacity seats available

Spiroindimicins B-D were isolated in 2012 from Streptomyces sp. SCSIO 03032,1 a deep-sea derived actinomycete collected from the Bay of Bengal. These hexacyclic natural products feature unprecedented [5,5] spirocyclic bisindole scaffolds, and exhibit moderate inhibitory activity and cytotoxicity against a series of cancer cell lines.1 To date there are no reports on the synthesis of any member of this unusual family of natural products. Our synthetic strategy involves a Fischer indolization between phenylhydrazine 1 and ketone 2 to form the pentacycle 3, to which we are currently attempting to append the pyrrole ring and hence complete the syntheses of spiroindimicins B-D.


ST Lecturers
avatar for Lachlan Blair

Lachlan Blair

Graduate Student, University of Auckland



Monday August 24, 2015 3:40pm - 4:00pm
Corwin West

3:40pm

[0019] Lewis acid-catalyzed cyclization reactions of amides of ethenetricarboxylates
Limited Capacity seats available

Nitrogen-containing heterocyclic systems are versatile core structures in organic chemistry because of their presence in many biologically active compounds. The development of new efficient synthetic strategies for the construction of nitrogen-containing heterocycles is of considerable interest. We have developed Lewis acid-promoted stereoselective five-membred ring formation of alkenyl ethenetricarboxylates.1 To promote the cyclization/halogenation, 1-2 equivalents of Lewis acids such as AlCl3, AlBr3, TiCl4, TiBr4 and ZnI2 are required. In this study, catalytic cyclization of allyl amides of ethenetricarboxylate leading to pyrrolidines has been examined. Reaction of allyl amides of ethenetricarboxylate with Sc(OTf)3 (0.2 equiv.) gave 4-hydroxymethyl-2-oxopyrrolidine derivatives stereoselectively (eq 1). The formation of the hydroxymethylpyrrolidines may arise from participation of water in situ. Sc(OTf)3-catalyzed cyclization reactions of the allyl amides with TMSX (X= Cl, Br) also proceeded efficiently to give halogenated 2-oxopyrrolidine derivatives. Catalytic cyclization of amides of ethenetricarboxylate bearing acetal and ether groups has also been examined. The reaction of the amides bearing cyclic acetal in the presence of Sc(OTf)3 gave piperidine derivatives as major products (eq 2). The cyclized products may be formed via internal redox process.2 Similarly, Lewis acid-catalyzed reaction of cyclic ethers gave spiro cyclic piperidine products selectively. The scope and the factors to control selectivities in the catalytic reactions of amides of ethenetricarboxylates are under investigation.


ST Lecturers
avatar for Shoko Yamazaki

Shoko Yamazaki

Professor, Nara University of Education
Professor Nara University of Education | Japan



Monday August 24, 2015 3:40pm - 4:00pm
UCEN Harbor

3:40pm

[0030] Amine Enables the Switching between Iminolactonization and Olefination
Limited Capacity seats available

The development of divergent reactions is one of the most challenging issues in metal-catalyzed reaction chemistry. Changing existing reaction patterns to other patterns by tuning the catalyst system suggests a new elemental step in the catalytic cycle. In this regard, we investigated a catalyst system that enables a perfect switch between iminolactonization and olefination. The reaction of alpha-bromoamides and styrenes underwent iminolactonization (carbo-oxygenation), in which simultaneous C–C and C–O bond formation occurred in the presence of a copper catalyst and triethylamine as a base, whereas olefination occurred in the presence of a copper catalyst and piperidine as a base

ST Lecturers
avatar for Takashi Nishikata

Takashi Nishikata

Associate professor, Yamaguchi University
associate professor | Yamaguchi University | Japan



Monday August 24, 2015 3:40pm - 4:00pm
UCEN State

3:40pm

[0045] Development of an Expedient Process for the Multi-Kilogram Synthesis of CHK1 Inhibitor GDC-0425
Limited Capacity seats available

As part of a recent drug development program for the orally active ChK1 inhibitor GDC-0425, we required multi kilogram amounts of active pharmaceutical ingredient (API) to support human clinical studies. The initial discovery chemistry synthesis involved a multi-step conversion from 6-chloro-5-fluoro-9H-pyrrolo[2,3-b:5,4-c']dipyridine 1. This route effectively provided initial quantities of API but used undesirable reagents (SEM, NaH, TBAF), high catalyst loadings and required tedious workup and isolation procedures. We set out do develop a first generation process to manufacture ChK1 inhibitor GDC-0425 on multi-kilogram scale. An important part of our process development also needed to address the removal of heavy metals and the development of a crystallization process for the isolation of the penultimate API in high purity.

This presentation will discuss our efforts to secure an efficient and scalable route to the API and steps taken to lead us to the optimal route for GDC-0425 as shown in the scheme below. Highlights of the talk will be the discussion of the (1) carbazole protection strategy, (2) development of an efficient Pd catalyzed cyanation of  aryl chloride 2; (3) optimization of the SNAr fluoride displacement of 3; (4) development of the recrystallization process for GDC-0425. The optimized process delivered highly pure API (>99 A% by HPLC) with the desired crystal form in an overall yield of 31 %.

ST Lecturers
avatar for Andy Stumpf

Andy Stumpf

Genentech
Scientist | Genetech 



Monday August 24, 2015 3:40pm - 4:00pm
Girvetz 2116

3:40pm

[0087] Catch & Release Drug Delivery System – Heterocycles, Bioorthogonal Chemistry and Implantable Biomaterials Optimize the Pharmacokinetics of Systemic Small Molecules
Limited Capacity seats available

Purpose: We present a heterocyclic-based drug delivery platform that optimizes the concentration of a systemic drug at a location of interest.  As a therapeutic proof of concept, we apply the system to the construction of an antibiotic agent based on vancomycin. 

Background:  Our prior studies have shown that an area of the body pre-implanted with a biomaterial containing a bioorthogonal reaction partner (trans-cyclooctene, TCO) can increase by ten times the local concentration of a heterocycle (tetrazine, Tz) carrying a radioactive payload in-vivo.  Now we present a platform that localizes and releases small molecules at the desired location (Fig. 1).

Methods/Results: We modified fluorophores and vancomycin with TCO and as well as synthesized an alginate biomaterial modified with tetrazine (Tz-gel).  We tested them through in-vivo and in-vitro models over multiple days.  The results indicate that the “Catch & Release” method can deliver an increased payload to a local area pre-implantated with the biomaterial.  The in-vitro therapeutic efficacy of the releasable vancomycin was comparable to vancomycin when tested in the presence of the Tz-gel against luminescent methicillin sensitive Staph. aureus (MSSA, Xen 29, Perkin Elmer, MA). 

Conclusions:  We present a drug delivery system that enables medical practitioners to direct drug to specific locations of the body by pre-implanting a biomaterial.  This system could have major implications to improve the therapeutic index of new and old drugs.

ST Lecturers
avatar for Jose M. Mejia Oneto

Jose M. Mejia Oneto

Founder, Shasqi
Orthopaedic Surgery Resident | Drug Delivery | Antibiotics | Chemotherapy



Monday August 24, 2015 3:40pm - 4:00pm
MCC Theater

3:40pm

[0095] Visible light mediated deoxygenation and decarboxylation as key step for the synthesis of tetrahydrofurans and pyrrolidines
Limited Capacity seats available

Polyols, amino alcohols and amino acids are readily available from renewable resources in enantiomerically pure form. Using such compounds as a starting point, we have developed the synthesis of novel tetrahydrofurans and pyrrolidines utilizing visible light mediated photoredox catalyzed deoxygenations and decarboxylations as key step.  The scope and limitation of this strategy in combination with the development of novel photoredoxcatalysts will be discussed.

ST Lecturers
avatar for Oliver Reiser

Oliver Reiser

Professor of Chemistry, University of Regensburg
Professor, | University of Regensburg, | Regensburg, Germany



Monday August 24, 2015 3:40pm - 4:00pm
Corwin East

3:40pm

[0127] Merging Enamine Catalysis with Hard Metal Lewis Acid Catalysis for Asymmetric Organic Transformations
Limited Capacity seats available

The development of new catalytic systems for new carbon-carbon and carbon-heteroatom bonding forming reactions has been a long-lasting research interest. The combination of organocatalysis with metal catalysis is an emerging field, aiming to achieve organic transformations that cannot be achieved through organocatalysis or metal catalysis alone. My research group has been engaged in developing new asymmetric reactions through combining enamine catalysis with hard metal Lewis acid catalysis.1-2 The biggest challenge in combining enamine catalysis with hard metal Lewis acid catalysis is the acid-base quenching reaction leading to catalyst inactivation. In this talk, I will present two strategies developed in our laboratory to synergistically incorporate enamine catalysis with hard metal Lewis acid catalysis. The first strategy is to use competition coordination to solve the critical acid-base quenching problem; the second strategy is to use the inversion of soft/hard approach to solve the acid-base quenching problem. Using these two strategies, we have developed a number of new asymmetric reactions including inverse-electron-demand asymmetric oxo-Diels-Alder reaction of ketones and multicomponent aza-Diels-Alder reaction of ketones.

ST Lecturers
avatar for Hong Wang

Hong Wang

Professor | Miami University | USA



Monday August 24, 2015 3:40pm - 4:00pm
UCEN Flying A

3:40pm

[0140] The simple and versatile synthesis of tetrasubstituted pyrroles and subsequent functionalization
Limited Capacity seats available

The cycloaddition–retroelectrocyclization reaction is a useful reaction for the conversion of electron-rich alkynes and electron-poor alkenes into buta-1,3-dienes.1 We have recently shown that this reaction is more widely applicable to ester-substituted alkenes to afford compounds of type 1.2 In this presentation we will describe how compounds of type 1 can be efficiently and rapidly converted into highly substituted pyrroles 2. Further one-step functionalization allows isolation of substituted pyrroles of type 3 and, 4 and 2H-pyrrol-2-ones 5, the latter of which exhibit strong chromophoric behaviour and a bathochromic shift upon protonation

ST Lecturers


Monday August 24, 2015 3:40pm - 4:00pm
UCEN Lobero

3:40pm

[0165] 1-Aza-3,4-diphospholides - Synthesis, Structure and Reactivity
Limited Capacity seats available

Na(OCP) has been shown to be a versatile precursor for a variety of compounds.[1,2] The versatility and the easy synthesis make this salt a powerful building block. The anion can act as a P− transfer agent [3] and the unsaturated CºP bond can undergo cyclo-addition reactions [4]. Two equivalents of Na(OCP) react with imidoyl chlorides to form 1-aza-3,4-diphospholides in good yields up to 80%. These electron rich diphsopholides were oxidized with hexachloroethane to from the phosphorus coupled dimers. 

The reactivity of Na(OCP) towards imidoyl chlorides was transferred to 2-chloro-pyridines and its derivatives. The result is a variety of new products with outstanding properties. The light absorption and emission are easily tuned by the substituents in the backbone. Further studies on the use of those ring systems as building blocks for chelating ligands, and electronic materials will be presented. 

[1] Puschmann, F. F. et al., Angew. Chem. Int. Ed., 2011, 50, 8420.

[2] Jupp, A. R., Goicoechea, J. M., J. Am. Chem. Soc., 2013, 135, 19131.

[3] Tondreau, A., Benkö, Z., Harmer, J., Grützmacher, H., Chem. Sci., 2014, 5, 1545.

[4] Benkö, Z., Grützmacher, H., et al., Angew. Chem. Int. Ed., 2014, 53, 1641.


ST Lecturers
avatar for Riccardo Suter

Riccardo Suter

PhD Student, ETH Zurich



Monday August 24, 2015 3:40pm - 4:00pm
Girvetz 2115

3:40pm

[0174] Tuberculosinyl Adenosines: Novel Terpene Nucleosides from Mycobacterium tuberculosis
Limited Capacity seats available

Tuberculosis (TB) remains a leading cause of death worldwide, resulting in 1.5 million deaths annually and yet no rapid, sensitive, and specific diagnostic test exists. Recently two novel terpene nucleosides were isolated from Mycobacterium tuberculosis (MTb) which were identified as 1-tuberculosinyl adenosine (1-TbAd) and N6-tuberculosinyl adenosines (N6-TbAd). In this presentation the first asymmetric total synthesis of the TbAd molecules will be discussed together with the development of specific diagnostic tests for MTb.


ST Lecturers


Monday August 24, 2015 3:40pm - 4:00pm
Girvetz 2119

4:00pm

[0004] Asymmetric Synthesis of alpha-Quaternary Substituted Aziridine-2-carboxylates and Application to Amino Acid Synthesis
Limited Capacity seats available

 A general, scalable, and highly diastereoselective aziridination of N-tert-butanesulfinyl ketimino esters is described.  The methodology has been utilized to provide straightforward access to novel, biologically relevant α-quaternary amino esters and derivatives starting from readily available precursors.


ST Lecturers
avatar for Maurice Marsini

Maurice Marsini

Senior ScientistBoehringer Ingelheim Pharmaceuticals | August 2011 – Present (3 years 10 months)Ridgefield, CT -Developed and executed an efficient, GMP synthesis of an API candidate utilizing Continuous/Flow Chemistry on 50 kg scale. | -Acted as Chemical Development liaison and provided scale-up support to colleagues for various activities during Pharmaceutical Development. | -Provided scale-up support to colleagues in Discovery... Read More →



Monday August 24, 2015 4:00pm - 4:20pm
MCC Theater

4:00pm

[0016] Synthesis of Nitrogen Analogues of Bioactive Lignans
Limited Capacity seats available

1,4-Benzodioxane neolignans are natural products that are a subclass within the lignan family that exhibit remarkable biological effects, including antimicrobial, hepaprotective and cytotoxic activities. In particular, 1,4-benzodioxane lignans with a 9-hydroxymethyl group such as silybin A, one of the components of silymarin (milk thistle extract), have shown inhibitory activity against hepatotoxicants. Nitidanin isolated from Santalum album is an antimalarial agent.

Previous work in our group has developed an enantioselective and flexible synthetic method to produce 1,4-benzodioxanes lignans such as eusiderin and  isoamericanin. We now report our efforts to synthesise nitrogen analogues of 1,4-benzodioxane lignans. The synthetic strategy is to convert the 1,4-benzodioxane skeleton into a benzomorpholine. The added nitrogen will allow an additional site for substitution which could allow bio-conjugation and also increase solubility.

We report our synthetic approach towards aza-lignans involving Mitsunobu reaction of an enantiopure secondary alcohol and an amino protected phenol, giving chirally pure aryl ethers which are converted into a benzomorpholine aminol. The N-Boc and O-Bn aminol was then subjected to N-acyliminium aryl addition, under acid condition. Aryl nucleophiles that are found in natural products were added to give a range of aryl benzomorpholine. Functionalization of the aryl bromide in these aryl benzomorpholines allows addition of the side chain.


ST Lecturers
avatar for Eunkyung Jung

Eunkyung Jung

PhD student, University of Auckland



Monday August 24, 2015 4:00pm - 4:20pm
Girvetz 2116

4:00pm

[0052] Palladium-Catalyzed Amidation by Chemoselective C(sp3)-H functionalization: Concise Route to Oxindoles and its application
Limited Capacity seats available

The oxindole moiety is a core structure in many complex natural products; such natural products often possess interesting biological activities. This structure has also drawn the attention of medicinal chemists because of its potential as an important pharmacophore. In the course of the synthetic studies of spirooxindole skeleton, we focused on the utilities of carbamoyl chloride, which undergo oxidative addition to palladium catalyst. If C(sp3)-H bond activation is occurred after the oxidative addition, oxindoles would be accessed concisely. When we started the project, several groups reported the related cyclization using palladium catalyst via C(sp3)-H bond activation of a methyl group and the following reductive elimination. Thus, we examined the formation of oxindoles from carbamoyl chloride bearing an alkyl group in proper position.

The cyclization of carbamoyl chloride (R1 = Me, R2 = H), which was prepared 2,6-dimethylaniline, proceeded smoothly under the conditions of palladium acetate (3 mol%), di(1-adamantyl)- n-butylphosphine (6 mol%), Cs2CO3 and N-hydroxypivalamide in mesitylene at 120 °C to give oxindole in 88% yield (eq. 1). These conditions could be applied to several substrates having chloro, methoxy groups and so on. Further studies to disclose the reaction scope and apply to the synthesis of natural products are currently underway and will be reported.

 


ST Lecturers
avatar for Chihiro Tsukano

Chihiro Tsukano

Lecturer, Kyoto University
Lecturer, Kyoto University, Graduate School of Pharmaceutical Sciences (2014-present)



Monday August 24, 2015 4:00pm - 4:20pm
Corwin West

4:00pm

[0091] A Bioinspired Approach to Tricyclic Spiroacetal-fused gamma-Lactones
Limited Capacity seats available

A bio-inspired approach involving ring-contraction rearrangement of decanolides was developed for the synthesis of spiroacetal-fused γ-lactones and applied to the total synthesis of reported structures of cephalosporolides H and I and penisporolide B and their diastereomers.

ST Lecturers
avatar for Rongbiao Tong

Rongbiao Tong

The Hong Kong University of Science and Technology, Hong Kong University of Science and Technology
Assistant Professor | Department of Chemistry | The Hong Kong University of Science and Technology. | Clear Water Bay, Kowloon, Hong Kong, China



Monday August 24, 2015 4:00pm - 4:20pm
UCEN Harbor

4:00pm

[0092] Stereoselective Synthesis of Oxa- and Aza-cycles using Reactions of Alkynes
Limited Capacity seats available

In recent years, metal catalysed transformations of alkynes have gain prominence for the synthesis of oxa- and aza-cycles. However, their utility under metal free conditions is still under explored. In a programme directed at the stereoselective synthesis of oxa- and aza-cycles using vinylogous carbonates and carbamates, we demonstrated that the oxonium and iminium ion intermediates generated from these functional groups in the presence of Lewis acids can be trapped with alkynes giving stereoselective access to functionalized 2,3-disubstituted dihydrobenzofurans and indoline derivatives. The regioselectivity of alkyne iminium ion cyclization can be reversed using a tethered hydroxy group as nucleophile. Further, we have also developed divergent synthesis of N-fused indolylidine, indole, and indoline derivatives using alkyne-iminium ion cyclisation. Interestingly, trapping of vinyl cation intermediate generated after alkyne iminium ion cyclisation was found to be dependent on the Lewis/Bronsted acid and solvent used. This talk will highlight some details of these studies.


ST Lecturers
avatar for Santosh J. Gharpure

Santosh J. Gharpure

Associate Professor, Indian Institute of Technology Bombay, India
Dr. Santosh J. Gharpure graduated with an M.Sc. degree in 1996, from Indian Institute of Technology Bombay, Powai. He obtained Ph.D. from Indian Institute of Science, Bangalore working with Late Prof. A. Srikrishna in 2001. He held a post-doctoral position with Prof. P. Andrew Evans at Indiana University, Bloomington, U.S.A. Subsequently; he joined the Department of Chemistry, IIT Madras, Chennai in the year 2004. In 2012, he moved to... Read More →



Monday August 24, 2015 4:00pm - 4:20pm
Girvetz 2115

4:00pm

[0099] Protecting Group Free Enantiospecific Total Synthesis of Structurally Diverse Natural Products of Four Different Classes
Limited Capacity seats available

A simple, highly diastereoselective, Lewis acid catalyzed coupling of cyclic allylic alcohol with carbazole, resorcinol and indole derivatives has been developed. The method was applied for the enantiospecific total syntheses of structurally diverse natural products such as murrayamine-O, machaeriol-D, ∆8-THC, ∆9-THC, epi-perrottetinene and tetracyclic core of fischerindole and hapalindoles, having wide range of biological activities. Synthesis of both natural products and their enantiomers has been achieved with high atom economy, protecting group free manner and in less than 5 steps longest linear sequence in very good overall yield starting from R-(+) and S-(-)-limonene.


ST Lecturers
avatar for Dattatreya H. Dethe

Dattatreya H. Dethe

Professor, Indian Institute of Technology Kanpur, India
Ph.D: IISC Bangalore (1999-2005) | Advisor: | Post-doc: ICES, Singapore(Aug.2005-July 2008) | Advisor: Prof.K. C. Nicolaou



Monday August 24, 2015 4:00pm - 4:20pm
Corwin East

4:00pm

[0144] Asymmetric synthesis of β-lactams by gas phase pyrolysis
Limited Capacity seats available

The chiral methylenedioxolanone 1 is readily available from (S)-lactic acid but it has not been used as a dipolarophile for 1,3-dipolar cycloaddition before. Diarylnitrones 2 add stereoselectively to give spiro adducts 3, and when these are subjected to flash vacuum pyrolysis at 440 °C, they eliminate ButCHO and CO2 as shown to give b-lactams 4 via an oxacarbene rearrangment.

The enantiomeric methylenedioxolanone 5, conveniently available from (R)-alanine,1 gives products 6 of the opposite enantiomeric series. Synthesis and FVP of the example 7 affords the advanced Ezetimibe precursor 8, thus completing a formal total synthesis of this important cholesterol-lowering drug.


ST Lecturers
avatar for Alan Aitken

Alan Aitken

R Alan Aitken | Senior Lecturer | School of Chemistry | Purdie Building | North Haugh | St Andrews | KY16 9STUnited Kingdom



Monday August 24, 2015 4:00pm - 4:20pm
UCEN State

4:00pm

[0147] One-pot Synthesis of cyclic analogues of hexamethylenebis(3-pyridine)amide (HMBPA
Limited Capacity seats available

A series of cyclic analogues of hexamethylenebis(3-pyridine)amide was prepared based upon a Ugi-3CR and aza-Diels-Alder reaction as a post-functionalization in a one-pot process. A simple condensations of commercially available diamine and aldehydes followed by isonitrile -addition provides the oxazoles intermediates, finally an aza-Diels-Alder cycloaddition and ring-opening using maleic anhydride provides the desired compounds in modest overall yield (12 examples, 6-69%) in approximately 40 min using microwaves as the heat source and scandium (III) triflate as a catalyst.


ST Lecturers
avatar for Eduardo González-Zamora

Eduardo González-Zamora

Full Professor, Universidad Autónoma Metropolitana
Professor | Universidad Autónoma Metropolitana



Monday August 24, 2015 4:00pm - 4:20pm
UCEN Lobero

4:00pm

[0187] Organotextile Catalysis
Limited Capacity seats available

Throughout human history, textiles have been integral to daily life, but their exploration in catalysis has been negleted. We demonstrated a facile and permanent immobilization of organocatalysts on the textile nylon using ultraviolet light, which doesn’t require chemical modification for the immobilization. A Lewis basic, a Brønsted acidic, and a chiral organocatalyst immobilized on textile display excellent stability, activity, and recyclability for various reactions. High enantioselectivity (>95:5 er) can be maintained for more than 250 cycles of asymmetric catalysis. Practical and straightforward applications of textile organocatalysis may be beneficial for various fields by providing inexpensive and accessible functionalized catalytic materials.


ST Lecturers
avatar for Jiwoong Lee

Jiwoong Lee

Postdoc, University of California, Berkeley



Monday August 24, 2015 4:00pm - 4:20pm
UCEN Flying A

4:00pm

[0197] Epimerization-free Cu-catalyzed peptide activation and cyclization
Limited Capacity seats available

For peptide cyclization C-terminal carboxyl activation is mandatory. In general, peptide C-terminal activation is accompanied by partial epimerization. By replacing the traditional coupling reagents by the Cu-catalyzed Chan-Lam reaction mildly activated peptide aryl-esters were obtained that were cyclized with complete stereocontrol.


ST Lecturers


Monday August 24, 2015 4:00pm - 4:20pm
Girvetz 2119

4:20pm

Walkabout
Find your way back to the invited talks, or perhaps switch rooms

Monday August 24, 2015 4:20pm - 4:40pm
TBA

4:40pm

[0081] Synthesis of Hybrid-1,5 Disubstituted Tetrazoles by Ugi-azide Reaction
Limited Capacity seats available

Multicomponent reactions (MCR) are powerful tools toward the synthesis of a large variety of interesting scaffolds even heterocycles. MCR are defined as one pot processes in which three or more reagents are sequentially combined to afford products having the majority of the atoms present in the starting reagents. The main applications of MCR are in Diversity Oriented Synthesis (DOS) and Combinatorial Chemistry (CC). The most important MCR are the isocyanide-based multicomponent reactions (I-MCR) such as Ugi reactions e.g. the classic Ugi-4CR, Ugi-3CR, Ugi-Smiles, Ugi-Nenajdenko, Ugi-Interrupted (Groebke-Blackburn-Bienaymé), and Ugi-azide. This latter allows the synthesis of 1,5-disubstituted Tetrazoles of high interest in medicinal chemistry because their ability to adopt conformations of cis-amide bond of peptides. On this occasion, I will show my results lately published just regarding the use of the Ugi-azide reaction towards the synthesis of 1,5-disubstituted Tetrazole-based hybrid compounds and some of their applications, mainly in medicinal chemistry.


Invited Lecturers
avatar for Rocío Gámez-Montaño

Rocío Gámez-Montaño

Prof. Investigador Titular “A”, Universidad de Guanajuato
La Dra. María del Rocío Gámez Montaño realizo la Licenciatura en Q.F.B. en la Universidad Michoacana de San Nicolás de Hidalgo (U.M.S.N.H),  el posgrado en la Universidad Nacional Autónoma de México (UNAM) donde obtuvo el grado de Doctor en Ciencias Químicas (2001) con la especialidad en el área de Química Orgánica. En 2001-2002  realizo una estancia... Read More →


Monday August 24, 2015 4:40pm - 5:20pm
UCEN Flying A

4:40pm

[0094] Studies Toward the Synthesis of Daphnicyclidin A
Limited Capacity seats available

Daphniphyllum alkaloids are a family of complex, polycyclic natural products derived from evergreen shrubs in southern China.  The daphnicyclidins represent a subset of these alkaloids as exemplified by daphnicyclidin A (1).  A stereocontrolled synthesis of the tricyclic ABC ring system will describe the formation of the amine 2 via a novel nine-membered Z-enone.  The discussion will present methodology for an efficient preparation of a-linked bis-enones as well as novel features of reactivity directly leading to functionalized heterocyclic systems.  Applications of this methodology for synthesis of the condensed fulvene of 1 will be described.


Invited Lecturers
avatar for David R Williams

David R Williams

Professor and Harry G. Day Chair, Indiana University


Monday August 24, 2015 4:40pm - 5:20pm
Corwin West

4:40pm

[0129] Synthesis of a Highly Functionalized Octahydro-Isoindole-Based NK1 Receptor Antagonist
Limited Capacity seats available

Primarily associated with sensory neurons and located within specific areas of the central nervous system (CNS), neurokinin-1 (NK-1) is a member of the seven-transmembrane G-protein-coupled receptor family.  The tachykinin peptide Substance P is the natural ligand for NK-1 and has been implicated in the pathophysiology of a wide range of dieases including anxiety, asthma, cystitis, emesis, inflammatory bowel disease, migraine, movement disorders, pain, and psoriasis.  Merck has identified an octahydro-isoindole-based compound 1 which has significant binding affinity (sub-nanomolar) for the hNK-1 receptor.  Compound 1 contains five stereocenters: a central core possessing four contiguous all-trans stereocenters, a pendent bis(trifluoromethyl)benzylic ether, and a cyclopentenone moiety.  In order to fully evaluate this compound, an efficient and practical synthesis was required which would allow for the preparation of multi-kilogram quantities to support both pre-clinical and clinical development.  Key to the success of the preparation of 1 was control of the relative and absolute stereochemistry.  This presentation will address the evolution of a highly efficient asymmetric synthesis of 1.


Invited Lecturers
avatar for Jeff Kuethe

Jeff Kuethe

Principal Scientist, Merck & Co.


Monday August 24, 2015 4:40pm - 5:20pm
MCC Theater

4:40pm

[0213] α,β-Unsaturated Diazoketones as Useful Platforms in the Synthesis of Nitrogen Heterocycles
Limited Capacity seats available

Diazocompounds are a very interesting class of compounds that can promote a wide range of reactions, such as cyclopropanations, insertion reactions, ylide formation, dimerization and elimination reactions and formation of ketenes by the Wolff rearrangement, among others. An interesting class of these diazocompounds is the α,β-unsaturated diazoketones, which has received little attention when compared to the saturated ones due to the difficulty of its preparation by the usual existing methods. Herein, we would like to describe two methodologies for the preparation of α,β-unsaturated diazoketones with E and Z geometry employing new Horner-Wadsworth-Emmons reagents and their use as efficient platforms in the synthesis of pyrrolidines, indolizidines and piperidines. 


Invited Lecturers
avatar for Antonio Carlos Bender Burtoloso

Antonio Carlos Bender Burtoloso

Associate Professor, Universidade de São Paulo
Graduated in Chemistry from the Federal University of Rio de Janeiro (2001), MA in Natural Products Chemistry, Federal University of Rio de Janeiro (2002) and a PhD in Chemistry from the State University of Campinas (2006). In 2007, he finished his postdoctoral at TSRI (The Scripps Research Institute) under the guidance of Professor KC Nicolaou (synthesis of LMNO fragment of maitotoxine). In 2008, he was hired as an assistant professor of... Read More →

Monday August 24, 2015 4:40pm - 5:20pm
Corwin East

5:30pm

Poster Session A [0001 - 0115]
Limited Capacity seats available

The accepted posters listed below are contingent upon the presenter registering for the conference and completing steps 1-4 as outlined on <http://www.ishc-web.org>.   This is a tentative list that is subject to change.  Poster board #numbers will be assigned to the abstracts closer to the conference starting date.  If you have recieved an acceptace for your poster, and it is not listed under POSTER A or POSTER B, then please notify me.   The cork on the poster boards is 47 inches tall and 67.5 inches wide, (119 cm tall X 171 cm wide).
 
0018: 10 Step Asymmetric Total Synthesis and Stereochemistry of (+)-Dragmacidin D, Mr. Jeffrey Jackson,  jjackson@chem.ucsb.edu [USA}

0023:  Asymmetric synthesis of heterocyclic compounds and their synthetic applications by cyclic ylides formation followed by enantioselective addition sequences, Prof. Hiroyuki Suga, sugahio@shinshu-u.ac.jp  [Japan]

0024:  Synthesis of 2-formylpyrroles using a Maillard approach: Elucidation of the bioactive pharmacophore in traditional Chinese medicines , Mr. James Wood, jwoo165@aucklanduni.ac.nz,  [New Zealand]

0025:  Synthesis of Potent Anti-Inflammatory Fungal Macrolactones, Mr. Johannes Tauber, 
tauberj@uni-mainz.de [Germany]

0029:    Copper-Catalyzed Regioselective 2-Arylation of 5-Substituted Tetrazoles under Mild Conditions, Dr. Takuya Onaka  t-onaka@fujimoto-chem.co.jp   [JAPAN]

0035p:  Total Synthesis of Potent Anti-inflammatory Cyclic Peptides Solomonamide A & B, Mr. Kashinath Komirishetty, k.kashinath@ncl.res.in, [India]

0036:  Enantioselective 1,3-dipolar cycloadditions reaction of nitrones with α,β-unsaturated aldehydes promoted by a primary siloxy β-amino alcohol organocatalyst, Mr. Teppei Otuki, 14041014@mmm.muroran-it.ac.jp, [Japan]

0037:  Asymmetric Aldol reaction of isatins with alkanones using an amino amide organocatalys, Mr. Jo Kimura,  14041023@mmm.muroran-it.ac.jp, [Japan]

0039:  Synthesis of fluorescein derivatives by Multicomponent Friedel-Crafts reaction using Niobium pentachloride as Lewis acid, Mr. Bruno Henrique Sacoman Torquato da Silva, bruno_sacoman@hotmail.com, [Brazil]

0041:  Asymmetric Diels-Alder reaction of anthrones with dienophiles using a basic amino alcohol organocatalyst, Mr. Jun Kumagai,  14096007@mmm.muroran-it.ac.jp  [Japan]

0043:  Synthesis of tetraaryl-1,4-dihydropyrrolo-[3,2-b]pyrroles derivatives using niobium pentachloride, Mr. Lucas Michelão Martins  lmichelaomartins@yahoo.com [Brazil]

0047:  Investigation of Some Functionalization Reactions of 1-amino-5-aroyl-4-aryl-1H-pyrimidine-2-one/-thione compounds with dialkyl acetylenedicarboxylates and ethyl 2-chloroacetoacetate, Dr. elif Korkusuz  elifdus@hotmail.com [Turkey]

0050:  Unravelling the Organocatalytic Facet of Vasicine, Ms. Sushila Sharma, sushilasharma591@gmail.com [India]

0053:  Synthetic Studies Towards Citreoviranol, Ms. Rachelle Quach, rqua009@aucklanduni.ac.nz, [New Zealand]

0054:  Synthetic Studies Towards the Marine Toxin Portimine,  Mr. Harry Aitken, harry.aitken@auckland.ac.nz  [New Zealand]

0058:  Formal Total Synthesis of (±)-Cycloclavine, Ms. Natalie Netz  netz@uni-mainz.de [Germany]

0059:  Total Synthesis of (-)-Leuconoxine Featuring Mannich-type Intramolecular Cyclization and Chiral Phosphoric Acid-Catalyzed Desymmetrization, Dr. Kazuhiro Higuchi, khiguchi@my-pharm.ac.jp [Japan]

0060:  Development and application of 2-azanorbornylmethanols as a cage type amino alcohol organocatalyst, Ms. Ayumi Ogasawara, 11023033@mmm.muroran-it.ac.jp, [Japan]

0061:  Efficient Synthesis of Fused Imidazole Containing Ring Systems via Dual Oxidative Amination of C(sp3)-H bonds, Georgette Castanedo, georgie@gene.com [USA]

0063:  Convergent synthesis of the ent-ZA’B’C’D’ ring system of maitotoxin, Dr. Tatsuo Saito, tatsuo@mol.f.u-tokyo.ac.jp, [Japan]

0064:  One-pot synthesis of aryl thiophenes using NaHSO4/SiO2 and Na2CO3/SiO2, Ms. Mamiko Hayakawa, hayakawa.mamiko@nihon-u.ac.jp, [Japan]

0067:  Total Synthesis of (-)-Caprazamycin A,  Mr. Hugh Nakamura, nakamura.hugh.33r@st.kyoto-u.ac.jp  [Japan]

0071:  Novel 5-nitrosopyrimidines and their physicochemical properties, Mrs. Lucie Cechova, cechoval@uochb.cas.cz  [Czech Republic]

0074:  Efficient Synthesis of Nitrogen-containing Medium Rings with Ynamides,  Dr. Yousuke Yamaoka, yyamaoka@pharm.kyoto-u.ac.jp [Japan]

0075:  Development of new antiviral candidate molecules using organocatalyzed asymmetric Diels-Alder reaction of 1,2-dihydropyridines with dienophiles as a key reaction, Mr. RYOHEI TAKAGI, 15041038@mmm.muroran-it.ac.jp, [Japan]

0077:  Novel quercetin diacylglycosides as potent anti-MRSA and anti-VRE agents, Prof. KENJI SASAKI,  sasaki-k@cc.okayama-u.ac.jp [JAPAN]

0082:  Building blocks for the synthesis of oligopyrroles and indolo analogues, Mr. Ruisheng Xiong, ruisheng.xiong@kemi.uu.se, [Sweden]

0084:  Synthesis of 1,2-dihydroisoquinolines via radical cyclization and Chugaev elimination of (E)-N-(2-bromobenzyl)-N-(2-(phenylthio)vinyl)acetamide, Dr. Holber Zuleta, hozuleta_13@hotmail.com [Mexico]

0089:  Synthesis and in vitro NMR and phantom MRI studies of TEMPO-Glc and TEEPO-Glc, potential contrast agents for MRI, Mrs. Maiju Soikkeli, maiju-lotta.soikkeli@helsinki.fi, [Finland]

0090:  Development of Aminooxazoline Xanthene-based β-Amyloid Cleaving Enzyme (BACE1) Inhibitors with Improved Selectivity Towards Cathepsin D (CatD), Mr. Jonathan Low, low@amgen.com, [USA]

0097:  α,β-Peptides containing pyrrolidine-based β-residues as useful tools for neuropeptide Y receptor-subtype selectivity, Prof. Oliver Reiser, oliver.reiser@chemie.uni-regensburg.de [Germany]

0100:  One-step syntheses of 2-pyrrolidinones and 3-pyrrolidinones from α,β-unsatured diazoketones and amines, Mr. Rafael Dias, rafaelmafra@iqsc.usp.br, [Brazil]

0101:  An Efficient Process for the Synthesis of Perfluoroalkylated Benzazepines, Prof. Weiguo Cao, wgcao@staff.shu.edu.cn, [China]

0102:   Regioselective Synthesis, X-ray and DFT studies of new Indazolyl-thiazole derivatives, Dr. Ram Pal Chaudhary, rpchaudhary65@gmail.com, [India]

0103:  Biomimetic Approach toward the Total Synthesis of rac-2-(Acylmethylene)pyrrolidine Alkaloids, Dr. Tun-Cheng Chien, tcchien@ntnu.edu.tw, [Taiwan]

0106:  Simple and efficient alkylation of 1,3-dicarbonyl compounds and synthesis of 4H-chromenes using NaHSO4/SiO2, Prof. Tadashi Aoyama, aoyama.tadashi@nihon-u.ac.jp, [JAPAN]

0108:  Formation of quinoline skeleton from chalcone: The effect of amino protective group to the reactivity of 2-aminochalcone, Dr. Tomohiro Maegawa,  maegawa@phar.kindai.ac.jp [JAPAN]

0110:  Cross-dehydrogenative silylation of non-aromatic C-H bonds by an Earth-abundant metal catalyst, Ms. Kerry Betz, kerry.betz@gmail.com, [USA]

0113: Discovery of 4-Aryl-N-arylcarbonyl-2-aminothiazoles as Hec1/Nek2 Inhibitors. Part I: Optimization of In Vitro Potencies and Pharmacokinetic Properties,  Prof. Jiann-Jyh Huang, lukehuang@mail.ncyu.edu.tw  [Taiwan]


Monday August 24, 2015 5:30pm - 6:30pm
UCEN Lagoon Plaza

6:30pm

Dinner
Monday August 24, 2015 6:30pm - 7:30pm
Ortega Dining Commons
 
Tuesday, August 25
 

7:30am

Breakfast
Tuesday August 25, 2015 7:30am - 8:30am
Ortega Dining Commons

8:55am

Announcements
Morning announcements of issues and activities 

Tuesday August 25, 2015 8:55am - 9:00am
Corwin Pavilion

9:00am

[0079] Studies in Natural Product Synthesis
Limited Capacity seats available

There can be no more noble undertaking than the invention of medicines. Chemists that make up the engine of drug discovery are facing incredible pressure to do more with less in a highly restrictive and regulated process that is destined for failure more than 95% of the time. How can academic chemists working on natural products help these heroes of drug discovery – those in the pharmaceutical industry? With selected examples from our lab and others, this talk will focus on that question highlighting innovation in fundamental chemistry and new approaches to scalable chemical synthesis.

Plenaries and Awardees
avatar for Phil Baran

Phil Baran

Professor, Darlene Shiley Chair in Chemistry, Skaggs Institute for Chemical Biology
Education | · NIH Postdoctoral Fellowship, Harvard University, 2001 - 2003 | · Ph.D., The Scripps Research Institute, La Jolla, 2001  | · B.S., New York University, 1997 | | Awards | · Mukaiyama Award, 2014 | · MacArthur Fellowship, 2013 | · Royal Society of Chemistry Synthetic Organic Chemistry Award, 2013 | · ACS San Diego Section Distinguished Scientist Award, 2012 | · ISHC... Read More →



Tuesday August 25, 2015 9:00am - 10:00am
Corwin Pavilion

10:00am

Coffee Break
Tuesday August 25, 2015 10:00am - 10:20am
UCEN Lagoon Plaza

10:20am

[0204] Transcriptional Control of Cancer with Small Molecules: Towards Novel Therapeutics
Limited Capacity seats available

My lecture will describe our use of small molecules to discover a new mechanism to control aberrant transcription of key genetic programs in cancer. I will also describe our progress towards initiating first-in-class clinical trials based on our discoveries. Synthesis and development of precision targeting small molecules has played a key role in this project

Plenaries and Awardees
avatar for Matthew Shair

Matthew Shair

Professor, Harvard University
Matthew Shair was born and raised in Boston, Massachusetts. Although he explored other parts of the country during undergraduate (University of Rochester) and graduate school (Yale and Columbia Universities), he eventually returned home for a post-doctoral position and a faculty appointment at Harvard. While the research opportunities provided by Harvard are a continual source of enjoyment and motivation for Matt, part of his love for Boston... Read More →



Tuesday August 25, 2015 10:20am - 11:20am
Corwin Pavilion

11:20am

[0198] Fragment Coupling Using Bimolecular Free-Radical Reactions
Limited Capacity seats available

Convergent synthesis strategies are fundamental to the efficient preparation of complex organic molecules. As a result, reactions that achieve the high-yielding union of polyfunctional fragments have particular importance in the preparation of structurally intricate organic molecules. Especially demanding are fragment coupling reactions that form sp3-sp3 sigma bonds and two stereocenters. When the two stereocenters reside in different rings and at least one of these stereocenters is quaternary, the challenge is enhanced substantially. This lecture will discuss the previously under appreciated utility of bimolecular reactions of free radicals to couple structurally intricate fragments.


Plenaries and Awardees
avatar for Larry Overman

Larry Overman

Distinguished Professor of Chemistry, University of California, Irvine
Education | Ph.D., University of Wisconsin, 1969 | B.A., Earlham College, 1965 | | Academic Distinctions | 2011 UCI Medal, University of California, Irvine, American Chemical Society, Herbert C. Brown Award for Creative Research in Synthetic Methods, 2010, Tetrahedron Prize for Creativity in Organic Chemistry, 2008, The Nagoya Medal of Organic Chemistry, 2007, International Society of Heterocyclic Chemistry Senior Award, 2005, Ta-shue... Read More →



Tuesday August 25, 2015 11:20am - 12:20pm
Corwin Pavilion

12:30pm

Lunch
Tuesday August 25, 2015 12:30pm - 1:45pm
Ortega Dining Commons

2:00pm

[0013] Synthesis of Natural Products Containing Spiroketals
Limited Capacity seats available

Natural products have long been regarded as “Nature’s medicine chest” providing invaluable platforms for developing front-line drugs. The chemical structures of natural products have evolved over several millennia for a specific biochemical purpose and their molecular frameworks can be considered “privileged scaffolds.” This lecture will showcase how natural products that contain intricate spiroketal scaffolds can be synthesized thus providing a platform to develop novel anticancer and anti-obesity agents.

The virgatolides are a family of natural products containing a rare benzannulated 6,6-spiroketal moiety isolated in 2011 from Pestalotiopsis virgatula.1 Virgatolides A-C exhibit cytotoxicity against HeLa cells (IC50 ~ 20 µM). The first synthesis2 of virgatolide B is described. Phorbaketal A and alotaketal A are two pseudoenantiomeric natural products, containing a unique spiro-sesterterpenoid core structure.3,4 Phorbaketal A possesses moderate cytotoxicity against a range of cancer cell lines, as well as exhibiting osteoblast and mast cell differentiation activity and inhibition of fatty acid synthesis in the liver. Additionally, alotaketal A activates the cAMP signalling pathway at nanomolar concentrations. Our efforts directed towards the enantioselective syntheses of phorbaketal A and alotaketal A will be described.5

Invited Lecturers
avatar for Margaret Brimble

Margaret Brimble

Distinguished Professor School of Chemical Sciences, University of Auckland
Academic Qualifications | 1983 to 1985 | PhD in Chemistry, The University of Southampton, UK | | 1982 to 1983 | MSc in Chemistry with First Class Honours, The University of Auckland, NZ | | 1979 to 1981 | BSc in Chemistry, The University of Auckland, NZ


Tuesday August 25, 2015 2:00pm - 2:40pm
UCEN Flying A

2:00pm

[0031] Optimization of Pim Kinase Inhibitors: Heterocyclic Chemistry and Macrocycles in a Pyrrole Series of Compounds
Limited Capacity seats available

Pim-1, -2, and -3 are highly homologous and constitutively active serine/threonine kinases. The three Pim isoforms phosphorylate a diverse group of proteins with known roles in proliferation, survival, apoptosis, and differentiation. The identification of oncogene-driven aberrant Pim kinase overexpression in subsets of B-cell malignancies including lymphomas, leukemias, and multiple myeloma, as well as in subsets of solid tumors, has led to intense efforts to identify small molecule Pim kinase inhibitors. A high-throughput screen of our corporate compound collection identified a hit composed of a 1,5-naphthyridine connected to a 6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one. A hit-to-lead optimization campaign resulted in the identification of improved inhibitors based on quinoxaline and quinazolin-4(3H)-one cores. A series of macrocyclic inhibitors in which the quinoxaline core and the dihydro-pyrrolo[3,2-c]pyridinone were connected was also found to possess improved properties. The heterocyclic chemistry of dihydro-pyrrolo[3,2-c]pyridinones, dihydropyrrolo[3,4-b]pyrrolones, and quinazolin-4(3H)-ones will be described, as well as the approaches used to synthesize macrocycles. Finally, the preclinical characterization of the lead molecules and their potential as treatments of Pim-driven malignancies will be presented.


Invited Lecturers
avatar for Victor Cee

Victor Cee

Principal Scientist, Amgen
Harvard University | Ph.D., Organic Chemistry | 1997 – 2003 | Thesis Advisor: Professor David A. Evans | | University of Utah | BS, Chemistry | September 1993 – June 1997


Tuesday August 25, 2015 2:00pm - 2:40pm
MCC Theater

2:00pm

[0046] A Divergent Stereocontrolled Synthesis of the Enantiopure Tetracyclic Cores of Asparagamine A and Stemofoline via an Intramolecular 2-Propylidine-1,3-(bis)silane Bicyclization
Limited Capacity seats available

A concise and highly diastereoselective synthesis of the polyfused tetracyclic cores of the Stemoa alkaloids asparagamine A and stemofoline that relies on a 2-propylidine-1,3-(bis)silane bicyclization onto a enantiodefined pyrrolidine 2,5-di(cation) equivalent derived from L-malic acid will be described.  A crucial feature of this divergent synthetic approach involves the solvolysis of a transient and highly labile tertiary-propargylic lactamol trifluoroacetate in the strongly ionizing medium 5M LiClO4/Et2O. The acyliminium ion generated in this manner undergoes stereospecific interception by the aforementioned (bis)silane nucleophile (Scheme 1).

The second topic of this discussion will be concerned with highly diastereoselective metalloamination/cyclizations of zinc(II) hydrazides derived from the reaction of diethylzinc and N,N-dimethylhydrazinoalkenes. The resulting organozinc intermediates have been found to undergo facile allylation and acylation, in-situ, to provide the corresponding functionalized piperidines and pyrrolidines respectively (Scheme 2).


Invited Lecturers
avatar for Thomas Livinghouse

Thomas Livinghouse

Professor of Chemistry, Montana State University
B.S., University of California, Los Angeles, 1976; M.S., University of California, Los Angeles, 1977; Ph.D., Rice University, 1980; Postdoctoral, Stanford University, 1981. | | Awards and Professional Activities: | Departmental Scholar (Chemistry), 1974 - 1976 University of California, Los Angeles, CA; Rice Graduate Fellowship (Chemistry), 1976 - 1977, Rice University, Houston, TX; NIH Postdoctoral Fellow (Chemistry), 1979 - 1980, Stanford... Read More →


Tuesday August 25, 2015 2:00pm - 2:40pm
Corwin East

2:00pm

[0209] Brønsted Acid Catalysis - Concepts and Applications in the Synthesis of Heterocycles
Limited Capacity seats available

The development and application of metal-free catalysts has become an important topic in organic synthesis and catalysis. Recently, chiral Brønsted acids have been shown to be vital alternatives to metal catalysts and examples of highly enantioselective transformations have been reported. These reactions, similar to several enzymatic processes, proceed through ion-pair and hydrogen-bond activation. In this presentation our introduction to enantioselective Brønsted acid catalysis will be shown and new and valuable transformations will be highlighted. Additionally, efforts to delineate the general requirements for performing Brønsted acid as well as synergistic catalysis with the use of visible light or metals will be outlined and the applicability of these catalytic processes to the synthesis of natural product cores and heterocycles will be presented. 


Invited Lecturers
avatar for Magnus Rueping

Magnus Rueping

Professor, RWTH Aachen University


Tuesday August 25, 2015 2:00pm - 2:40pm
Corwin West

2:40pm

[0028] Synthesis of Poison-Frog Alkaloids
Limited Capacity seats available

A variety of lipid-soluble alkaloids have been detected in amphibian skin, which contains over 20 structural classes and over 800 alkaloids. Many of these poison-frog alkaloids are expected to show interesting biological activities such as inhibitory effects on the neuronal nicotinic acetylcholine receptors (nAChRs).

We envisioned an efficient and flexible synthesis of 5,8-disubstituted, 6,7-dehydro-5,8-disubstituted, and 5,6,8-trisubstituted indolizidines, 1,4-disubstituted quinolizidines, decahydroquinoline-type poison-frog alkaloids using a Michael-type conjugate addition reaction of an enaminoester as the key step as shown below.


Invited Lecturers
avatar for Naoki Toyooka

Naoki Toyooka

Professor, University of Toyama
| Kinki University, Faculty of Pharmaceutical Science  University, 1984.03, Graduated, JAPAN | | | Kinki University, Graduate School, Division of Pharmaceutical Sciences. Doctor's Course, 1989.03, Completed, JAPAN | | | University of Toyama Graduate School of Science and Engineering Nano and Functional Material Sciences Functional Molecule Production Systems, Professor, 2010.04 - | | | University of Toyama Faculty of... Read More →


Tuesday August 25, 2015 2:40pm - 3:20pm
Corwin East

2:40pm

[0104] Elucidation of the Structure and Stereochemistry of the Metabolites of the HCV Protease Inhibitor Faldaprevir
Limited Capacity seats available

Faldaprevir is an HCV Protease Inhibitor for the treatment of Hepatitis C infection.  The first small molecule treatment for HCV, the macrocycle BILN 2061, was the predecessor of Faldaprevir. Human clinical isolates following administration of Faldaprevir were found to contain four major human metabolites.  Elucidation of the structure of each of these metabolites was achieved through a combination of isotopic labelling, LC-NMR, HPLC-MS, global esterification/chromatography and total synthesis.  Implications for the molecular-level inetractions of the drug in the Cyp-3A4 active site will also be discussed.


Invited Lecturers
avatar for Carl Busacca

Carl Busacca

Distinguished Research Fellow, Boehringer Ingelheim
Boehringer Ingelheim | November 1994 – Present (20 years 4 months) | | Chemist | Sterling Winthrop | January 1990 – November 1994 (4 years 11 months) | Rensselaer, NY | | Colorado State University | Doctor of Philosophy (Ph.D.), Organic Chemistry | 1985 – 1989


Tuesday August 25, 2015 2:40pm - 3:20pm
MCC Theater

2:40pm

[0116] Domino Strategies for Syntheses of Natural Products and New Molecular Scaffolds
Limited Capacity seats available

Our group has been engaged in designing simple and efficient domino strategies for the syntheses of natural products and natural product like molecules. In this lecture, our efforts leading to syntheses of vinigrol, cyclic guanidines and N-heterocyclic amides will be discussed in details.

Vinigrol, a unique diterpene, containing the decahydro-1,5-butanonaphthalene carbon skeleton has been shown to exhibit a broad spectrum of biological activity. Besides the multiple sites of oxygenation, vinigrol contains a tricyclic core having a cis-fused [4.4.0] system bridged by an eight-membered ring and eight contiguous stereocenters. We recently reported an enantioselective formal synthesis of vinigrol, involving a 1-2-3 strategy (one pot and 2-reactions with the formation of 3-rings), leading to the core structure of vinigrol from its stereochemically well-defined acyclic precursor.

The cyclic guanidines and N-heterocyclic amides are important structural units present in biologically active drug molecules. However, the existing methods suffer from harsh conditions, narrow functional group tolerance, poor atom economy, low yielding and so; it warrants an efficient protocol for their syntheses. We have developed a one-pot Cu-catalyzed cascade routes to these unique cyclic guanidines and N-heterocyclic amides from readily available starting materials

Invited Lecturers
avatar for Krishna Kaliappan

Krishna Kaliappan

Professor of Chemistry, Indian Institute of Technology
Place and Date of birth | Kallidaikurichi, TN. March 1968  | | Education  July 1988 – June 1990M.Sc. (Organic Chemistry Specialization)School of Chemistry, Madurai Kamaraj University June 1985 – May 1988B.Sc. (Chemistry), Madurai Kamaraj University   | | Research Experience  April 1999 - March 2001Post doctoral Fellow, Duke University (Advisor: Prof. Michael Pirrung) April 1997-March... Read More →


Tuesday August 25, 2015 2:40pm - 3:20pm
UCEN Flying A

2:40pm

[0215] Molecular Rearrangements of Furan Heterocycles
Limited Capacity seats available

Materials derived from non-edible renewable resources, ideally by-products in food production processes, are valuable starting materials for chemistry. One such raw material, furfural, is produced from hemicellulose derived from agricultural waste products like bagasse, oat hulls and corncobs. Environmentally benign stock-chemicals are important to sustainable development by ensuring a future supply of raw materials. Our group has studied the molecular rearrangement of furfural and its derivatives to streamline the synthesis of molecular building blocks, including a novel class of photochromic material.  In this lecture, we will present the development of this chemistry and highlight recent applications of the photochromic material as sensors and their use in light-controlled cargo delivery. 


Invited Lecturers
avatar for Javier Read de Alaniz

Javier Read de Alaniz

Associate Professor, University of California
Javier Read de Alaniz joined the department of Chemistry and Biochemistry at UC, Santa Barbara in 2009. Born and raised in Las Vegas, New Mexico, he received his B.S. degree from Fort Lewis College (Durango, Colorado) in 1999 where he conducted undergraduate research under the direction of Professor William R. Bartlett. He obtained his Ph.D. under the supervision of Professor Tomislav Rovis at Colorado State University in 2006. His doctoral... Read More →

Tuesday August 25, 2015 2:40pm - 3:20pm
Corwin West

3:20pm

Coffee Break
Limited Capacity seats available

Tuesday August 25, 2015 3:20pm - 3:40pm
UCEN Lagoon Plaza

3:40pm

[0011] Rapid Composition of Tricyclic Spiranoid Lactones: Access to Natural and Unexplored Frames
Limited Capacity seats available

Many important biochemical compounds and drugs of natural origin contain tricyclic spirofuranone ring structures. Analysis of their molecular frames shows a compacted carbon skeleton with angularly fused tricycles of different oxidation states in each of the rings, which together present a real synthetic challenge.

Based on the remarkable core structure similarities among the natural products, we designed a rapid and practical collective synthesis strategy of complex functionalized natural and never-before explored frames. We devised a general and common synthesis of phylogenetically and structurally different tricyclic angularly fused systems via controlled cyclizations of simple key precursors. The novel strategy is short, regio- and stereoselective, and offers the possibility to access a broad spectrum of quaternary carbon-centered spiranoid lactone-based structures. Readily accessible key molecules, which are of lesser complexity than the target natural products, were elaborated by simple synthetic sequences. These yield a broad spectrum of spiranoid lactones of varying complexity.

Only a few of the naturally occurring ring fusion combination sets (mostly five- or six-membered rings) across a broad spectrum of the angularly fused spiranoid lactones are known to exist. Other combinations are extremely rare or do not exist at all. Our methodology enables us to produce new variations of angularly fused structures, providing access to a wide range of compounds that have never before been available and observed. These compounds closely resemble common natural scaffolds and carry potential for becoming valuable drugs/therapeutic agents.

We believe that novel concept will reshape the idea of spiranoid lactone moieties as building blocks in multistep synthesis, thus enabling completely innovative retrosynthetic analyses. Importantly, the application of the invented strategy to easily accessible building blocks will allow for the straightforward preparation of complex systems.

 


ST Lecturers
avatar for Dmitry Tsvelikhovsky

Dmitry Tsvelikhovsky

Ph.D. SENIOR LECTURER, Hebrew University of Jerusalem
Academic Secretary of MCS-ICS | Medicinal Chemistry Section of the Israel Chemical Society | | Laboratory of Organic Synthesis and Methodology | Institute for Drug Research, | School of Pharmacy, R 416-a, | Faculty of Medicine, Campus Ein Karem | The Hebrew University of Jerusalem | Jerusalem 91120, ISRAEL



Tuesday August 25, 2015 3:40pm - 4:00pm
Corwin East

3:40pm

[0022] Enantiospecific coupling of secondary and tertiary boronic esters
Limited Capacity seats available

A great amount of research has been dedicated in recent decade towards developing methods that facilitate the construction of 3D scaffolds of molecules. This comes as a direct consequence of a realisation that saturated molecules interact better with biological receptors than flat, unsaturated structures. There is a strong interest from pharmaceutical industry as it hopes to explore undiscovered chemical space using saturated molecules. Scientific community is investing a lot of effort to enable this goal, mainly by utilisation of established methods such as Suzuki-Miyaura cross-coupling. This Nobel Prize winning process has opened doors to a wide range of stereospecific reactions that enable the synthesis of tertiary carbon centres with high enantiomeric enrichment. This talk will focus on a new process developed in Aggarwal group that allows for the synthesis of tertiary and all-carbon quaternary centres in a transition metal free transformation

ST Lecturers
avatar for Marcin Odachowski

Marcin Odachowski

University of Bristol
MChem University of Manchester, UK | Currently: PhD student at University of Bristol, UK



Tuesday August 25, 2015 3:40pm - 4:00pm
Girvetz 2112

3:40pm

[0038] Synthesis and Fungicidal Activity of Substituted 1-(1-tert-butyl-1H-imidazol-4-yl)-1H-1,2,3-triazoles
Limited Capacity seats available

A series of new 1-(1-tert-butyl-1H-imidazol-4-yl)-1H-1,2,3-triazoles were prepared by reactions of corresponding 1-(1-tert-butyl-3-nitroazetidin-3-yl)-1H-1,2,3-triazoles with triethylphosphite with further oxidation. The 1,4-disubstituted triazoles were obtained by addition of azides to substitude acetylenes in the presence of ascorbic acid and copper(II) sulfate. Their structures were confirmed by  1H, 13C NMR, IR, X-Ray, HRMS and elemental analysis. Most of the synthesized compounds were screened in vitro for their antifungal activity against Rhizoctonia solani, Fusarium oxysporum, Fusarium moniliforme, Fusarium graminearum, Sclerotinia sclerotiorum, Venturia inaequali and Bipolaris sorokiniana. Some of the compounds displayed activities comparable with those of the commercial fungicide Triadimefon. 


ST Lecturers
avatar for Mikhail Dubovis

Mikhail Dubovis

Chemist, Mendeleyev University of Chemical Technology of Russia



Tuesday August 25, 2015 3:40pm - 4:00pm
UCEN State

3:40pm

[0040] Targeting Vector Borne Tropical Infectious Diseases with Heterocyclic Compounds
Limited Capacity seats available

There is a pressing need to develop effective drugs for the treatment of vector borne infectious diseases such as malaria and chikungunya. In our research reported here, we utilise two strategies for lead identification. The nature products approach led to two heterocyclic scaffolds for anti-plasmodial drug development while data-mining identified thieno[3,2-b]pyrroles as potential anti-virals against chikungunya. This presentation will provide an overview of our synthetic and biological discoveries in this field. 


ST Lecturers
avatar for Christina Chai

Christina Chai

Associate Professor and Principal Scientist, National University of Singapore and Institute of Chemical and Engineering Sciences
Christina Chai obtained her BSc (Hons) from the University of Canterbury, Christchurch, New Zealand and her PhD in synthetic organic chemistry from the Research School of Chemistry, Australian National University, Canberra under the mentorship of the late Professor Athel Beckwith, FRS. Following her PhD, she was awarded a Samuel and Violette Glasstone Research fellowship at the University of Oxford, UK where she studied bioorganic reaction... Read More →



Tuesday August 25, 2015 3:40pm - 4:00pm
Girvetz 2115

3:40pm

[0062] Ortholactone Spiroketal Fragment Couplings: A Convergent Approach to Complex Natural Products.
Limited Capacity seats available

Spiroketals are ubiquitous in nature occurring in many complex macrolides which exhibit potent biological activity. Most methods for their construction are linear approaches requiring long synthetic sequences to install functional groups prior to a cyclization to form the spiroketal. Although effective, these methods are not convergent and lead to high linear step counts and issues with both material throughput and structure diversification.1 Our approach was to develop a modular fragment-coupling based strategy whereby the sprioketalization is also the fragment coupling step. This convergent approach uses the coupling of an ortholactone and a δ-hyroxyallylsilane to form the sprioketal in a single step, a strategy reported by Markó on very simple substrates.2

The major synthetic challenges were to develop an efficient and functional group tolerant synthesis of ortholactones followed by optimization of the fragment coupling in complex systems. The ortholactone synthesis was achieved through a palladium catalyzed Wacker-type oxidation of dihydropyrans.3 This method was particularly efficient for the construction of both methoxy and spirocyclic variants. These ortholactones could be coupled very efficiently with the allylsilanes to form the spiroketals in high yields as a single stereoisomer. When Bi(OTf)3 was used as a Lewis acid, a fragmentation reaction occurred to form a rearranged γ-lactone product which occurs with a wide range of functionality.

ST Lecturers
avatar for Matthew Cook

Matthew Cook

Queen's University Belfast
LecturerOrganic ChemistryQueen's University Belfast 



Tuesday August 25, 2015 3:40pm - 4:00pm
Corwin West

3:40pm

[0080] Asymmetric Conjugate Addition of Alkylzirconocenes to Cyclopentene-3,5-dione Monoacetals
Limited Capacity seats available

Many methodologies have been developed in recent years but fail to address the challenges of cyclopentenones.2 Our group demonstrated that the conjugate addition of alkylzirconocenes to cyclohexenone derivatives is advantageous (Scheme 1a).3 However, when applying the methodology conditions to cyclopentenones, the yield was poor (23%) and the ee dropped (to 75%). Feringa et al. reported4 the derivatisation of cyclopentene-3,5-dione monoacetal 1 with diakylzinc reagents (Scheme 1b) in moderate yield (40%) and high ee (90%). The yield was significantly improved (to 69%) when trapping an aldehyde.

ST Lecturers
avatar for Emeline Rideau

Emeline Rideau

Graduate Student, University of Oxford



Tuesday August 25, 2015 3:40pm - 4:00pm
Girvetz 2116

3:40pm

[0107] Practical Synthesis of N-Substituted Cyanamides as N-C-N Building Blocks for Heterocycle Synthesis
Limited Capacity seats available

A variety of carboxamidoximes (2), prepared from carbonitriles with NH2OH, could react with benzenesulfonyl chlorides (TsCl or o-NsCl) and DIPEA to form N-substituted cyanamides (3) in very good yields. The benzenesulfonyl chlorides promoted Tiemann rearrangement of carboxamidoximes (2) is readily amenable for the synthesis of a wide variety of cyanamide derivatives in multi-gram scales from carbonitriles.1 Acidic hydrolysis of the N-substituted cyanamides (3) afforded the corresponding N-monosubstituted ureas (4) in good yields. The preparation of the N-monosubstituted ureas (4) could also be accomplished in a one-pot fashion effectively from carbonitriles (2) with comparable yields.2 N-Alkyl-N’-arylguanidines (5) could be obtained from the reaction of N-arylcyanamides (3) with various primary and secondary alkylamines, under the catalysis of CuI and Xantphos in DMF. This methodology provides a direct access to versatile N,N’-disubstituted guanidine derivatives (5) from previously described N-arylcyanamides (3).3 The application of N-substituted cyanamides (3) toward the synthesis of various heterocycles, including benzimidazoles, benzoxazoles, and quinazolinones, has also been demonstrated.

ST Lecturers
avatar for Tun-Cheng Chien

Tun-Cheng Chien

Associate Professor | National Taiwan Normal University | Taipei Taiwan



Tuesday August 25, 2015 3:40pm - 4:00pm
UCEN Flying A

3:40pm

[0123] Small Molecules for Treatment of Retinal Degenerative Diseases
Limited Capacity seats available

Retinitis Pigmentosa (RP) is a family of progressive retinal degenerative diseases that effects small populations. The diseases are associated with many different genes hindering drug development – there are currently no treatments. We have hypothesized that metabolic stress is downstream to many of the gene mutations. Recently, a high throughput screen (HTS) was developed under conditions that mimic RP.[i]   Hits from this primary screen were then subjected to a second assay that measures mitochondrial flux capacity, addressing the oxidative stress component affiliated with this neurodegenerative process. Two of these hits, CB11 and CB12, come together to form a pharmacophore from which novel chemical entities were synthesized.  From these efforts, a small panel of analogs were developed and tested as a means to optimize protection of mitochondria from metabolic stress.  Achieving cellular protection via the cell’s “power house” offers a novel approach towards treating this disease and the potential for addressing other pathologies where mitochondria are part of the degenerative process. 

[i]           Beeson, Craig Cano; Rohrer, Baerbel; Perron, Nathan R. Compositions and methods for the treatment of degenerative diseases  PCT Int. Appl. (2011), WO 2011119869 A1 20110929

 


ST Lecturers
avatar for Christopher Lindsey

Christopher Lindsey

MitoChem Therapeutics Inc.
Director MitoChem Therapeutics Inc.,  Medical University of South Carolina  



Tuesday August 25, 2015 3:40pm - 4:00pm
MCC Theater

3:40pm

[0146] Synthesis of Highly Functionalized 4-Aminoquinolines
Limited Capacity seats available

A method for the synthesis of highly functionalized 4-aminoquinolines from sulphynamides and amides is presented. The amides are activated by triflic anhydride (Tf2O) and 2-chloropyridine (2-ClPy) and, as Movassaghi et al. have shown, can be used to prepare a wide range of heterocyclic structures.[1] Sulphynamides can be prepared using copper catalysis and alkyl bromides[2] and further derivatized by using Sonogashira chemistry.[3] The main challenge in existing quinoline syntheses is the functionalization at the C-2 and C-3 positions. By combining the Sonogashira approach with the ynamide/amide methodology a wide range of substitutions at C-3 is possible and the C-2 and C-5 to C-8 positions are also accessible. In order to show the broad applicability of the methodology, it was found that the ynamides also readily react with paracyclophane-based amides, creating very interesting planar chiral compounds.


ST Lecturers
avatar for Tim Wezeman

Tim Wezeman

Karlsruhe Institute of Technology
PhD Student / Marie Curie Fellow with Prof. Stefan Bräse | Involved in ynamide chemistry, currently working on 4-aminoquinolines



Tuesday August 25, 2015 3:40pm - 4:00pm
Girvetz 2119

3:40pm

[0169] Development of Chiral Auxiliaries and Catalysts from Proline Hydantoin
Limited Capacity seats available

Our research program is focused on designing chiral reagents and catalysts for applications in asymmetric synthesis based on structural frameworks that have been under-exploited for lack of practical syntheses. Recent work has focused on the use of L-proline hydantoin (1) as a common starting material for the preparation of variously substituted imidazolone precursors (2) to N-heterocyclic carbenes (NHCs), including N-ferrocenyl imidazolones (3). Stereoselective induction of planar chirality in the latter molecules has enabled synthesis of iridium complexes bearing unusual NHCs (e.g., 4) that catalyze asymmetric hydrogenation of quinolines at low hydrogen 

ST Lecturers
avatar for Costa Metallinos

Costa Metallinos

Associate Professor | Department of Chemistry | Brock University | St. Catharines, Ontario | L2S 3A1



Tuesday August 25, 2015 3:40pm - 4:00pm
UCEN Lobero

3:40pm

[0186] Practical Asymmetric Electrophilic Amination of Silyl Enol Ether Derivatives via the Nitrosocarbonyl Ene Reaction
Limited Capacity seats available

Presented is an account of the first example of a general asymmetric nitrosocarbonyl ene reaction with silyl enol ether derivatives. The procedure is operationally simple and utilizes an easily accessible chiral nitrosocarbonyl precursor (EleNOr), catalytic copper, and air as a benign oxidant. The transformation is both high yielding and highly diastereoselective for a variety of silyl enol ether derivatives including aromatic heterocyclic ketones. A range of non-exclusive post-functionalizations showcases the variety and scope of this method’s potential synthetic applications.


ST Lecturers


Tuesday August 25, 2015 3:40pm - 4:00pm
UCEN Harbor

4:00pm

[0012] Total and Formal Syntheses of Heterocyclic Natural Products and Drugs by Matsuda-Heck-Reaction
Limited Capacity seats available

The palladium catalysed Matsuda-Heck-Reaction or arene diazonium salts is a powerful synthetic tool for the coupling of olefins and (heterocyclic) aryl compounds. Highlighted by mild reaction conditions, convenient synthesis[2,3] of very reactive and extremely useful electrophiles, this C-C-bond forming reaction is a highly versatile and efficient reaction for the synthesis of complex structures[4].

To the best of our knowledge, we report the first total syntheses of three known bioactive heterocyclic natural compounds[5,6] and one formal synthesis[7] of the anti-migraine drug Naratriptan, which are presented below. Furthermore, we developed new synthetic pathways for the novel olefins and arene diazonium tetrafluoroborates required, optimized the systems and implement the results in very efficient and atom economic routes.

Our reaction conditions are distinguished by low catalyst loading of inexpensive Pd(OAc)2, short reaction times, excellent functional group tolerance, absence of bases and ligands, full stereoselectivity and good to excellent yields.


ST Lecturers
avatar for Felix Wolf

Felix Wolf

Ph.D. Student, University of Potsdam



Tuesday August 25, 2015 4:00pm - 4:20pm
Corwin West

4:00pm

[0017] Transition Metal-Catalyzed Cyclization of Enediynes to Benzopyranones, Carbazoles and Benzothiophenes
Limited Capacity seats available

Recently, we found that treatment of N,N-dimethyl 2-[(2-(2-alkynylphenyl)ethynyl)anilines 1 with ten mol% of PdCl2 and two equivalents of CuCl2 at refluxing THF for one hour gave the chlorinated benzo[a]carbazoles 2 in excellent yields. The chloroindoles 3 was proposed as the key intermediate and can be prepared separately by reaction of 1 with two equivalents of CuCl2 at refluxing THF. Treatment of 3 with various electrophilic transition metals, such as PdCl2, Pd(OAc)2 and PtCl2, gave carbazoles 2 in good yields. Under the similar reaction conditions, methyl 2-[6-substituted 3(Z)-hexen-1,5-diynyl]benzoates and 2-(2-(2-(2-substituted ethynyl)phenyl)ethynyl)thioanisoles were converted to dibenzo[b,d]pyran-6-ones and benzo[b]naphtho[2,1-d]thiophenes, respectively.


ST Lecturers
avatar for Ming-Jung Wu

Ming-Jung Wu

Professor, | Department of Chemistry, | National Sun Yat-sen University 



Tuesday August 25, 2015 4:00pm - 4:20pm
UCEN Flying A

4:00pm

[0069] Fragment-Based Approach Toward Lactate Dehydrogenase A (LDHA) Inhibitors
Limited Capacity seats available

A fragment based approach was used to identify a unique series of LDHA inhibitors with good ligand efficiencies.  Subsequent optimization delivered a novel lead series with LDHA cellular activity of 10 μM, selectivity against LDHB, and good physicochemical properties.  The overall strategy of identification and optimization, lessons learned, and some guiding principles of the FBDD effort will be presented in the context of the discovery of a fragment-derived lead series for the inhibition of LDHA.

 “All studies were conducted in accordance with the GSK Policy on the Care, Welfare and Treatment of Laboratory Animals and were reviewed the Institutional Animal Care and Use Committee either at GSK or by the ethical review process at the institution where the work was performed.”


ST Lecturers
avatar for Beth Knapp-Reed

Beth Knapp-Reed

Investigator, GlaxoSmithKline
Investigator GlaxoSmithKline



Tuesday August 25, 2015 4:00pm - 4:20pm
MCC Theater

4:00pm

[0105] Teaching an old dog new tricks: chemical biology studies of pyrroloquinazolines
Limited Capacity seats available

7H-Pyrrolo[3,2-f]quinazoline-1,3-diamine (1) is a privileged chemical scaffold with significant biological activities. These include inhibition of dihydrofolate reductase (DHFR), protease-activated receptors (PAR) and protein tyrosine phosphatase 1B (PTP1B). However, the currently accessible chemical space derived from 1 is rather limited. In this presentation, we expanded the chemical space related to 1 by developing efficient methods for regioselective monoacylation at N1, N3 and N7, respectively. With this novel methodology, a focused library of mono-N-acylated pyrroloquinazoline-1,3-diamines were prepared and screened for anti-breast cancer activity. The structure-activity relationship (SAR) results showed that N3-acylated compounds were in general more potent than N1-acylated compounds while N7-acylation significantly reduced their solubility. Among the compounds evaluated, LBL1 possessed significantly more potent activity than 1 in MDA-MB-468 cells. More importantly, LBL1 was not toxic to normal human cells. Further chemical biology and mechanistic studies showed that LBL1 targets nuclear lamins to inhibit repair of double-strand DNA breaks (DSB) in breast cancer cells. The discovery of LBL1 as the first lamin-binding ligand from a focused novel library of 1 supports that 1 is a privileged scaffold. The availability of LBL1 should enable us to address the poorly understood molecular mechanisms of lamins in DSB repair processes

ST Lecturers
avatar for Xiangshu Xiao

Xiangshu Xiao

Associate Professor, Oregon Health & Science University
Associate Professor | Physiology and Pharmacology | Oregon Health & Science University  | 3181 SW Sam Jackson Park Rd  | Portland, OR  97239 



Tuesday August 25, 2015 4:00pm - 4:20pm
UCEN Lobero

4:00pm

[0112] Enantioselective Synthesis of Fully Functionalized Chiral Hemiaminals
Limited Capacity seats available

ST Lecturers
avatar for Hongming Li

Hongming Li

Associate Principle Scientist, Merck
Associate Principle Scientist Merck



Tuesday August 25, 2015 4:00pm - 4:20pm
UCEN State

4:00pm

[0121p] Indole Directed C-H Activation: Direct Synthesis of Functionalized Carbazole from Indoles via Triple C-H Activation
Limited Capacity seats available

ST Lecturers
avatar for Akhilesh Kumar Verma

Akhilesh Kumar Verma

Professor, University of Delhi / SPS, JNU, India
Ph. D- (Chemistry), Department of Chemistry, University of Delhi, India Year: 2000 | Advisor- | Post. Doc- : Jan. 2001‐December 2002 University of Florida, Gainesville, FL, USA | Advisor- Prof. Alan R. Katritzky | Current position- Professor in Department of Chemistry, University of Delhi



Tuesday August 25, 2015 4:00pm - 4:20pm
Corwin East

4:00pm

[0124] Production of Antimicrobial Silver and Magnetite nanoparticles Using Natural Products based on Rosin And Murrh Gums
Limited Capacity seats available

In the present study, new silver and magnetic nanoparticles were prepared using modified cationic, nonionic surfactants and amino-amidoximes based on rosin as natural products[2, 3].  The produced modified rosin surfactants and amino-amidoximes were used as capping agents for magnetite nanoparticles to prepare hydrophobic coated magnetic powders[4-6].  Water soluble carbohydrates produced from Murrh natural gum were used to produce capped magnetite and silver nanoparticles as natural gums. A new class of monodisperse amphiphilic magnetite  and silver nanoparticles were  prepared by a simple and inexpensive green method. 

The structure and morphology of magnetite  and silver capped with modified  rosin  and Murrh gums   were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), zeta potential, thermogravimetric analysis (TGA) and dynamic light scattering (DLS). The magnetic properties were determined from vibrating sample magnetometer (VSM) analyses. These prepared  silver and magnetite nanoparticles were tested as bioactive nanosystems and their antimicrobial effects were investigated. 


ST Lecturers
avatar for Hamad Al-Lohedan

Hamad Al-Lohedan

Professor | King Saud University | Riyadh | Saudi Arabia



Tuesday August 25, 2015 4:00pm - 4:20pm
Girvetz 2112

4:00pm

[0175] Synthesis and application of 2-substituted 1,1-diphenyl-2,4-dihydro-1H-benzo[d][1,3]oxaphosphinin-1-ium
Limited Capacity seats available

In the presence of Ph3PBr2 or Ph3PHBF4, 2-substituted 1,1-diphenyl-2,4-dihydro-1H-benzo[d][1,3]oxaphosphinin-1-ium can be synthesized from (2-(diphenylphosphino)phenyl)methanol and an aldehyde in 36-89% yields. These phosphonium salts are bench-stable solids and undergo Wittig olefination with another aldehyde under basic condition (K2CO3 or t-BuOK) to form benzylic vinyl ethers, which are readily hydrolyzed to 1,2-disubstitued ethanones under acidic condition. Therefore, the overall reaction provides a facile route to couple two aldehydes to form 1,2-disubstituted ethanones

ST Lecturers


Tuesday August 25, 2015 4:00pm - 4:20pm
Girvetz 2116

4:00pm

[0177] Discovery and Optimization of Novel Inhibitors of the Mitochondrial Permeability Transition Pore
Limited Capacity seats available

The mitochondrial permeability transition pore (mtPTP) is a Ca2+-requiring megachannel that permanently opens under pathological conditions and leads to deregulated release of Ca2+ and mitochondrial dysfunction. For the past couple of decades the mtPTP has been implicitly recognized as a therapeutic target for several deadly diseases such as Alzheimer’s disease, muscular dystrophies, myocardial infarction, stroke, and diabetes. Herein we report the results of a high-throughput screening/chemical optimization approach that led to the discovery of two new chemotypes: (a) diarylisoxazole-3-carboxamides and (b) N-phenylbenzamides, which are first subnanomolar inhibitors of the mtPTP. The therapeutic potential and in vivo efficacy of the most potent analogues were validated in a biologically relevant zebrafish model of collagen VI congenital muscular dystrophies.


ST Lecturers
avatar for Sudeshna Roy

Sudeshna Roy

Postdoctoral Fellow in Medicinal/Organic Chemistry at University North Carolina at Chapel Hill (current), The University of Kansas (past). Advisor Prof. Jeffrey Aubé Ph.D. in Organic Chemistry in 2012. Advisor Prof. C. D. Spilling at University of Missouri-St. Louis. Research Interests: Medicinal chemistry involving development of small molecule therapeutics for diseases related to mitochondrial dysfunction as well as other novel targets... Read More →



Tuesday August 25, 2015 4:00pm - 4:20pm
Girvetz 2119

4:00pm

[0211] Towards Chemoselective Arylation Reactions of Peptides Using Triarylbismuthanes
Limited Capacity seats available

There is a need for general methods that lead to post-synthetic modification of peptides. Currently, few methods exist for the chemoselective arylation on specific amino acid residues. Organobismuth reagents have recently gained interest due to their versatility in bond formation, functional group tolerance, low cost and low toxicity related to the inorganic bismuth salt. Recently, our group has developed efficient arylation methods using highly functionalized trivalent arylbismuth reagents to form C‒C, C‒O and C‒N bonds.1 In particular, indoles, phenols and aminoalcohols have been successfully arylated in good to excellent yields via substoichiometric copper catalysis in mild conditions. As a result, this method will be further employed as a mean of selective arylation of polypeptides. In this poster, we will present our progress in the development of arylation methods of peptides using triarylbismuthanes.

 


ST Lecturers


Tuesday August 25, 2015 4:00pm - 4:20pm
Girvetz 2115

4:00pm

[0218] An Efficient Synthesis of Tetrahydroimidazo[1,2-a]pyrazines via Tandem Multicomponent Reaction
Limited Capacity seats available

Isocyanide based multicomponent reactions (IMCRs) followed by cyclization have become a valuable tools of drug discovery oriented synthetic heterocyclic chemistry since they allow synthesizing diverse nature-like heterocyclic small molecules in simple one-pot procedures. Recently we have developed IMCR of various primary diamines and carbonyl compounds that leads to a wide variety of heterocyclic scaffolds with pyrazine, quinaxoline, hetarenopyrazine, 1,4-diazepine, 1,4-benzodiazepine, and other pharmaceutically relevant cores [1].

Here we report post-condensation modification of the discovered IMCR by involving of dimethyl isocyanoacetal as a bifunctional isocyanide component. This enables further cyclization of intermediate pyrazine-2-amines 4 into target imidazopyrazines 5 under acidic conditions. Since no purification is required for intermediates 4, the entire synthesis can be performed in one-pot mode. 

Notably, imidazopyrazine core of general formula 5 is a key structural feature of orexin receptor antagonists (2012), kappa receptor agonists, mGluR5 modulators, and TrkA inhibitors.

Scope of the developed tandem reaction including its expansion for the synthesis of spiro-imidazopyrazines and tetrahydroimidazo[1,2-a][1,4]diazepines as well as its application for small molecule libraries synthesis will be discussed.

[1] Kysil, V. et al. Eur. J. Org. Chem. 2010, 1525–1543.




ST Lecturers
avatar for Volodymyr Kysil

Volodymyr Kysil

Director of Chemistry, ChemDiv, Inc.
MS/BS 1980, Kyiv National Taras Shevchenko University, Ukraine | Ph.D. 1989, Kyiv National Taras Shevchenko University, Ukraine | Previous work: 1980 – 2002, Sr. Research Scientist, Kyiv National Taras Shevchenko University, Ukraine | My research interests focus on medicinal chemistry oriented synthesis of heterocyclic compounds, novel synthetic methodologies including multicomponent and domino reactions, the design of small molecule... Read More →



Tuesday August 25, 2015 4:00pm - 4:20pm
UCEN Harbor

4:30pm

ISHC Members' Meeting
Limited Capacity filling up

Tuesday August 25, 2015 4:30pm - 5:30pm
Corwin West

5:30pm

Poster Session B [0116 - 0215]
Poster board #numbers correspond to your abstract number.  If you have registered and recieve an acceptace for your poster, and it is not listed under POSTER A or POSTER B, then please notify me.  The cork on the poster boards is 47 inches tall and 67.5 inches wide, (119 cm tall X 171 cm wide).

0118 (w):  Total synthesis of (3R,16E,20E,23R)-eushearilide, Dr. Takayasu Yamauchi, yamauchi@hoshi.ac.jp [Japan]

0119:  Synthetic Studies on Renieramycin T, an Antitumor Marine Natural Product, Dr. MASASHI Yokoya, yokoya@my-pharm.ac.jp, [Japan]

0120:  Study on interaction of novel heteroaryl chalcones with calf thymus DNA using molecular docking and spectroscopic techniques, Mr. Paresh Patel, pareshn111@yahoo.com, [India]

0125:   A novel [3+2] cycloaddition reaction of allenoate and isoquinoline, Prof. Xueshun Jia, xsjia@mail.shu.edu.cn, [China]

0126:  Design of a Free Radical Process Based Upon Xanthate Chemistry to Produce New Synthetic and Optically Active (α and β) Amino Acids,  Holber Zuleta-Prada, hozuleta_13@hotmail.com, [Mexico]

0130:  Sequential Ugi/Palladium-Catalyzed Aerobic Oxidative Cyclization: novel TetrahydroIndeno[1,2-b]Pyrrolidines Synthesis, Dr. Tannya R. Ibarra-Rivera,  tannyaibarra@gmail.com,  [Mexico]

0131: Structure-Activity Relationship of Matrine Type Alkaloids Part 24; Synthesis and Antinociception of 3-Arylpiperidine Derivatives, Mr. Hiroyoshi Teramoto, d203@hoshi.ac.jp, [Japan]

0133:  A Green and Efficient Protocol for the Synthesis of NovelPyrazolo[3,4-b]quinolines via a One-pot, Three-component ReactionUnder Solvent-free Conditions, Prof. Majid Heravi, mmh1331@yahoo.com, [Iran]

0136:  One-pot two-step cross-coupling approach towards the synthesis of novel unsymmetrical polycarbo-substituted imidazo[1,2-c]quinazolines, Ms. Tebogo Khoza, khozata@unisa.ac.za, [South Africa]

0137:  Sequential Michael Addition and Enamine-Promoted Inverse Electron Demanding Diels-Alder Reaction upon 3-Vinyl-1,2,4-Triazine Platforms, Prof. Franck Suzenet, franck.suzenet@univ-orleans.fr, [France]

0139:  Synthesis of functionalized indoles under continuous flow conditions, Dr. Frédéric Buron, frederic.buron@univ-orleans.fr, [France]

0143:   A new synthesis of heterocycles from o-subsituted aryl benzyl ethers,  Dr. Alan Aitken, raa@st-and.ac.uk, [United Kingdom]

0145:  Synthesis of pyrazine-pyrane-dithiolene complexes mimicing specific features of the molybdenum cofactor (MoCo),  Ms. Claudia Schindler, claudia.schindler@uni-greifswald.de, [Germany]

0148:   Preparation and Reactions of 2-Functionalized-4, 5-diaryloxazoles: Synthesis of Extended Diaryloxazole Scaffolds, Dr. Frederick Luzzio, faluzz01@louisville.edu, [USA]

0152:  A Concise and Atom-Economical Suzuki-Miyaura Coupling Reaction Using Unactivated Trialkyl- and Triarylboranes with Aryl Halides, Dr. Yong-Li Zhong, yongli_zhong@merck.com. [USA}

0153:   Regioselective functionalizations of thiazolotriazoles and imidazothiadiazoles, Dr. Sylvain Routier, sylvain.routier@univ-orleans.fr, [France]

0154:  Synthesis of cotinine and iso-cotinine analogs using an Ugi-4CR approach, Prof. Alfredo Vazquez,  joseavm@unam.mx [Mexico]

0157:  Synthesis of Aminocyclopentitol Analogues,  Mr. Han Pyo Son,  nochase@skku.edu [Korea]

0161:  Total Synthesis of (—)-Codonopsinine, Mr. Jun Min Jung, jdiablo@skku.edu [Korea]

0166:  Acyclic Nucleoside Phosphonates Containing A Second Phosphonate Group As Potent Inhibitors Of 6-Oxopurine Phosphoribosyltransferases With Antimalarial Activity, Mr. Petr Spacek, petr.spacek@uochb.cas.cz,  [Czech Republic]

0168:  Triazole synthesis by alkyne-azide cycloaddition using silver catalysis, Dr. EUGENIA JOSEFINA ALDECO PEREZ, eugeniajosefina@yahoo.com [Mexico]

0170:  Laboratory and practical synthesis of Suvorexant, a selective dualorexin receptor antagonist, Mr. Satoyuki Takahara, fairyjowl@gmail.com [Japan]

0171:  The second generation strategy of oligosaccharide synthesis via asymmetric intermolecular hydroalkoxylation of alkoxyallene, Ms. Soyeong Kang, sykang@postech.ac.kr, [Korea]

0172:  Stereodivergent Synthesis of Decahydroquinoline-Type Poison Frog Alkaloids -Part 1, Mr. Takuya Okada, m1471303@ems.u-toyama.ac.jp [Japan]

0173:  Stereodivergent Synthesis of Decahydroquinoline-Type Poison Frog Alkaloids -Part 2, Mr. Takuya Okada, m1471303@ems.u-toyama.ac.jp [Japan]

0175:  Synthesis and application of 2-substituted 1,1-diphenyl-2,4-dihydro-1H-benzo[d][1,3]oxaphosphinin-1-ium, Dr. Wenhua Huang, huangwh@tju.edu.cn, [China]

0176:  Synthesis of promising understudied heteroaromatic scaffolds for the drug discovery process, Mr. Paulo Eliandro da Silva Junior, paulo.silva@fcfrp.usp.br, [Brazil]

0178:  Mimicking the Molybdenum Cofactor by Synthesis of Molybdenum-Pterin Complexes, Mr. Ivan Trentin, ivan.trentin@uni-greifswald.de [Germany]

0179:  Synthesis of planar-chiral phase-transfer catalysts incorporating hydroxyl methyl pyridinophane moieties and their use for catalytic asymmetric reaction, Mr. SEIJU KOMAKI, 
sjkomaki@fuji.waseda.jp [Japan]

0180:  Total synthesis of (±)-azaspirene and racemization in aqueous media, Dr. TAKAHIRO HASEGAWA, hasegawa133@asagi.waseda.jp [Japan]

0182:  Hydrazine-Catalyzed Direct Inverse Electron Demand Diels-Alder Reactions of 1,3,5-triazines with Ketones, Mr. Kai Yang, yangkai12@mails.jlu.edu.cn [China]

0183:  Mylated Protein Isolates of some underutilized oil seeds and their Functional Properties, Dr. Joan Ogundele, joan.ogundele@fuoye.edu.ng, [Nigeria]

0184:  New solvent-free synthesis of norbornenes derived from maleimides, Dr. Adilson Beatriz, adilson.beatriz@ufms.br [Brazil]

0185:  Reversible Oxidation of 40π Antiaromatic Expanded Isophlorins into a Polaron Pair, Dr. Neelam Shivran, neel2k1@gmail.com, [India]

0186:  Practical Asymmetric Electrophilic Amination of Silyl Enol Ether Derivatives via the Nitrosocarbonyl Ene Reaction, Mr. Andrey Samoshin, asamoshin@chem.ucsb.edu [USA]

0190:  New access to bicyclic heterocyclic structures bearing a fused nitropyrazole, Mr. Thibaud Alaime, thibaud.alaime@cea.fr, [France]

0191:  New Methods for Amide Bond formation and Oxazole Synthesis, Ms. Aysa Pourvali, aysap@student.unimelb.edu.au, [Australia] 

0211:  Towards Chemoselective Arylation Reactions of Peptides Using Triarylbismuthanes, Mr. Martin Hébert, hebert.martin_jean-guy@courrier.uqam.ca, [CANADA]

0212:  Investigation of the regioselectivity of thermal cyclization reactions in gas and liquid phase high temperature flow reactors, Dr. Heather Graehl, heather.graehl@thalesnano.com [USA}

Tuesday August 25, 2015 5:30pm - 6:30pm
UCEN Lagoon Plaza

6:30pm

Dinner
Tuesday August 25, 2015 6:30pm - 7:30pm
Ortega Dining Commons
 
Wednesday, August 26
 

7:30am

Breakfast
Wednesday August 26, 2015 7:30am - 8:30am
Ortega Dining Commons

8:55am

Announcements
Wednesday August 26, 2015 8:55am - 9:00am
Corwin Pavilion

9:00am

[0005] Alan R. Katritzky Memorial Symposium "A 50 Year Infatuation/Obsession with 1,3-Dipoles"
Limited Capacity seats available

Alan Katritzky, who in 2014 died at the age of 85, was a pioneer in the field of heterocyclic chemistry, the study of molecules possessing rings of carbon atoms along with other elements.

For 60 years, his research was reported in more than 2,300 papers and 200 books – a prodigious output that proved to be of great value to the academic community as well as to the pharmaceutical and agrichemical industries. He maintained his remarkable output until a few days before his death.

Alan was born into a family of Polish immigrants in London. Evacuated in 1940 to Wisbech, Cambridgeshire, he acquired his passion for chemistry at Wisbech high school, preparing his first heterocyclic compound, the barbiturate drug Veronal, on his 15th birthday.

After gaining a first-class degree in chemistry, followed by a doctorate, at Oxford University, he moved to Cambridge University in 1957, becoming a foundation fellow of Churchill College.

In 1962, at the unusually early age of 34, he was appointed professor of chemistry and founding head of the school of chemical sciences at the newly established University of East Anglia in Norwich.

There he rapidly established an undergraduate teaching programme and a strong postgraduate research school, fostering close contacts with the chemical industry. Such practices have since become widely established.

In 1980, he left Norwich to become chair of chemistry at the University of Florida in the US, where he founded a Centre for Heterocyclic Compounds to encourage postgraduate study and to find industrial applications for discoveries in the field. The Katritzky family funded charitable foundations to support students and founded a free online journal, called Arkivoc, that provides researchers in the developing world with a vehicle to publish their work in.

Alan was forceful, direct and resolute in his professional life, and his commitment to his chosen subject was total. In his personal relationships, he was compassionate and warm.

He is survived by his wife, Linde, his children Rupert, Margaret, Erika and Freda, and three grandchildren, Martin, Eric and Elisabeth.

Al Padwa will provide a tribute to Professor Alan Katritzky’s remarkable career in heterocyclic chemistry.  In part 2, the chemistry of metal carbene complexes as a method to generate 1,3-dipoles is discussed. This approach bestows chemists with an exceptionally fertile ground for designing and developing new stereoselective bond construction for application toward the synthesis of various alkaloids. Due to their lability, metal carbene complexes are usually generated in situ from their corresponding diazo precursors prior to use.  The reaction of a-diazo carbonyl compounds with transition metals such as rhodium(II) carboxylates constitutes a particularly powerful method for generating synthetically useful electrophilic carbene complexes. Earlier work by our group has shown that the rhodium(II) catalyzed reaction of 2-diazo-3-oxobutanoates bearing tethered p-bonds represents a synthetically useful protocol for the construction of a variety of novel polycyclic skeletons. The Rh(II)-catalyzed reactions of the related 2-diazo-2-(1H-indol-2-yl)acetate system has now been examined as a potential route toward scandine, a member of the melodinus family of alkaloids. Attack of the neighboring carbonyl oxygen atom onto the rhodium carbenoid center produces a cyclic 1,3-dipole that undergoes cycloaddition with a tethered alkenyl group.  The resulting cycloadduct corresponds to a potential intermediate in a planned synthesis of scandine 



Plenaries and Awardees
avatar for Al Padwa

Al Padwa

William Patterson Timmie Professor of Chemistry, Emory University
<>ISHC Senior Fellow; B.A., Columbia University, 1959; Ph.D., Columbia University, 1962; Postdoctoral Research Fellow, University of Wisconsin, 1962-1963: Asst Prof Ohio State Univ (1963-1969); Assoc Professor SUNY Buffalo (1966-1969); Professor SUNY Buffalo (1969-1979); W. P. Timmie Professor Emory University (1979-present)<><> <> <>Al has held visiting positions at University Claude Bernard, France, Harvard... Read More →




Wednesday August 26, 2015 9:00am - 10:00am
Corwin Pavilion

10:00am

Coffee Break
Wednesday August 26, 2015 10:00am - 10:20am
UCEN Lagoon Plaza

10:20am

[0117] Synthesis of azabicyclic natural product analogues aiming at biological activity
Limited Capacity seats available

Many natural products with interesting biological activity contain azabicyclic or bridged nitrogen containing scaffolds. These conformationally restricted compounds are characterised by a considerable ring strain which may complicate ringclosing reactions.

The lecture will discuss ringclosing methodology for the synthesis of several classes of azabicyclic and azamulticyclic derivatives designed towards agrochemical or medicinal applications.

 

A dynamic ring closure has been deloped for the synthesis of 7-azabicyclo[2.2.1]heptanes. This skeleton is present in epibatidine, a very active analgesic compound isolated from the skin of the Ecuadorian frog Epipedobates tricolor. Its potency was proven to be 200-fold higher than morphine, however epibatidine cannot be used clinically because of its high toxicity. Different classes of epibatidine analogues have been prepared trying to minimize toxicity while maintaining the analgesic properties.

 

Gold catalysed ringclosing reactions have been developed for the synthesis of functionalised isoindoles, dehydrothiazoles and pyrroles.The ring closing involves a 5-exodig cyclization, followed by a [1,3]-alkyl shift and a [1,5]-H shift.

 

Diketopiperazines are well recognized as an important moiety in medicinal active secondary metabolites of plants. We developed a new cyclization for the straightforward synthesis of constrained diketopiperazine analogues of the brevianamide family. This new class of analogues with a 3,5-bridged structure and bearing an alfa-chloro amine function allows the synthesis of a library of compounds using a variety of nucleophiles. We also performed ab initio calculations to get insight on the mechanism of the DKP-tryptophane ring closure. 


Invited Lecturers
avatar for Christian Stevens

Christian Stevens

Professor of Chemistry, Ghent University
| Heterocyclic Synthesis | Microreactor Technology  | Chemical modification of Renewable Resources


Wednesday August 26, 2015 10:20am - 11:00am
Corwin Pavilion

11:00am

[0048] What are Heterocyclic Mesomeric Betaines?
Limited Capacity seats available

Our systematic analysis identifies five discrete classes and associated subclasses. Each general class and subclass has different structural properties and reactivity profiles. In particular, it is important to distinguish between Conjugated (Class 1), Cross-conjugated (Classes 2 & 4) and Semi-conjugated (Classes 3 and 5) mesomeric betaines. Representatives of some classes are well known, others are rare and examples of a few are unknown. Together they account for a large area of heterocyclic chemistry. The common features and significant differences of the betaines shown will be discussed and our recent studies of (i) the aromaticity of semi-conjugated mesomeric betaines and (ii) mesomeric betaine/N-heterocyclic carbene tautomerism will be described.  

Invited Lecturers
avatar for Christopher Ramsden

Christopher Ramsden

Emeritus Professor of Organic Chemistry, Keele University
I was born in Manchester, UK in 1946. I graduated from Sheffield University and received my PhD (W. D. Ollis) in 1970 and DSc in 1990. After post-doctoral work at the University of Texas (M. J. S. Dewar)(1971-3) and University of East Anglia (A. R. Katritzky)(1973-6), I worked in the pharmaceutical industry. I moved to Keele University as Professor of Organic Chemistry in 1992. My research interests are heterocycles and three-centre bonds and... Read More →


Wednesday August 26, 2015 11:00am - 11:40am
Corwin Pavilion

11:40am

[0208] Development and Application of StackPhos, A New Chiral Biaryl Heterocyclic Ligand for Enantioselective Catalysis
Limited Capacity seats available

The development of new chiral ligands for enantioselective catalysis continues to be an important research area as the products impact a broad range of disciplines driven by organic synthesis.  Our group has been involved in designing chiral biaryl P,N-ligands that incorporate a heterocycle into the biaryl backbone.  This lecture will cover the developments in my laboratory that lead to the design and implementation of StackPhos, an imidazole-based P,N-ligand with unique ligation properties and catalytic activity.

Invited Lecturers
avatar for Aaron Aponick

Aaron Aponick

Associate Professor of Chemistry, University of Florida
Aaron Aponick was born in Atlantic City, New Jersey in 1976 and grew up in Harrisburg, Pennsylvania.  He became interested in organic chemistry at  Lebanon Valley College where he studied reactions of quinones with organometallics under the guidance of the late Carl Wigal. After obtaining a B.S. in 1998 he moved to the University of Michigan and joined  the research group of Will Pearson.  At UM, where he was an Eastman... Read More →


Wednesday August 26, 2015 11:40am - 12:20pm
Corwin Pavilion

12:20pm

Free Time
Wednesday August 26, 2015 12:20pm - 6:30pm
TBA

12:30pm

Lunch
Tours depart at 1:30pm, after on-campus Lunch

Wednesday August 26, 2015 12:30pm - 1:45pm
Ortega Dining Commons

6:30pm

Dinner
Wednesday August 26, 2015 6:30pm - 7:30pm
Ortega Dining Commons
 
Thursday, August 27
 

7:30am

Breakfast
Thursday August 27, 2015 7:30am - 8:30am
Ortega Dining Commons

8:55am

Announcements
Opening Announcements

Thursday August 27, 2015 8:55am - 9:00am
Corwin Pavilion

9:00am

[0210] Recent Progress in the Synthesis of Natural Products
Limited Capacity seats available

Efforts in our laboratories focus on the synthesis of complex natural products.  Recent efforts directed toward syntheses of phomoidride D and hippolachnin A will be described

Plenaries and Awardees
avatar for John Wood

John Wood

Professor, Baylor University



Thursday August 27, 2015 9:00am - 10:00am
Corwin Pavilion

10:00am

Coffee Break
Thursday August 27, 2015 10:00am - 10:20am
UCEN Lagoon Plaza

10:20am

[0078] A. R. Katritzky Junior Award "Synthetic Studies on N-Heterocyclic Natural Products"
Limited Capacity seats available

Since nitrogen-containing heterocyclic rings are common structural motifs in biologically important natural products, development of new synthetic methodologies for construction of these structures have been one of the important research topics in synthetic chemistry. In this lecture, our recently completed total syntheses of polycyclic alkaloids featuring new synthetic strategies will be discussed. We investigated a reductive ring expansion of cyclic ketoximes and applied to a concise total synthesis of (–)-mersicarpine.1 For formation of substituted indolines, we developed a benzyne-mediated cyclization-functionalization sequence and applied this reaction to total syntheses of dictyodendrins A-E.2 A protective group free total synthesis of (–)-rhazinicine was accomplished based on the development of a gold-catalyzed double cyclization cascade.3 In the first total synthesis of (+)-haplophytine, we constructed the characteristic spiroaminal by an oxidative semi-pinacol type rearrangement.4 Dihydrooxepin rings in (–)-acetylaranotin was formed by combination of the vinylogous Rubottom oxidation and the Baeyer-Villiger ring expansion of an enone intermediate.


Plenaries and Awardees
avatar for Hidetoshi Tokuyama

Hidetoshi Tokuyama

Professor, Tohoku University
Education | Tokyo Institute of Technology, Ph.D., Chemistry, 1994 | Tokyo Institute of Technology, B.S., Chemistry, 1990 | | Awards | 2011 Nagase Foundation Award 2011 | 2009 Lectureship Award (Thailand), The 4th International Conference on Cutting-Edge Organic Chemistry in Asia | 2009 Lectureship Award (China), The 4th International Conference on Cutting-Edge Organic Chemistry in Asia | 2007  Young Scientist's Prize: The Commendation for... Read More →



Thursday August 27, 2015 10:20am - 11:20am
Corwin Pavilion

11:20am

[0155] E. C. Taylor Senior Award: Synthesis of Heterocycles By Cyclizations and Functionalizations
Limited Capacity seats available

In general, the synthesis of complex biologically active molecules are problematic but the problems, encountered during the syntheses, can be a good source of inspiration to develop methods. One major challenge is the design of concise strategies as well as chemoselective and efficient methods that rapidly lead to the skeleton framework of natural and/or biologically active heterocyclic compounds.

In this context, we have explored the construction of heterocycles using catalytic reactions involving transition metal catalysts and heat. Metal catalysts and heat can induce rearrangements, cyclizations, functionalizations which can be highly diastereoselective and enantioselective if a chiral ligand is added in the reaction media. These reactions and their applications to the synthesis of heterocyclic natural and non-natural products will be presented

Plenaries and Awardees
avatar for Janine Cossy

Janine Cossy

Professor, ESPCI
Professor Janine Cossy graduated from the University of Reims working under the supervision of Prof. Jean-Pierre Pète. After a postdoctoral stay with Prof. Barry Trost (1980-1982) at the University of Wisconsin, she returned to Reims where she became Director of Research of the CNRS in 1990. The same year, she moved to Paris to become Professor of Organic Chemistry at the Ecole Supérieure de Physique et de Chimie Industrielles de la... Read More →



Thursday August 27, 2015 11:20am - 12:20pm
Corwin Pavilion

12:30pm

ISHC Committee Lunch
Limited Capacity seats available

The GSA lounge for the committee meeting is upstairs in the Multicultural Center


Thursday August 27, 2015 12:30pm - 1:30pm
GSA Lounge (adjacent MCC)

12:30pm

Lunch
Thursday August 27, 2015 12:30pm - 1:45pm
Ortega Dining Commons

2:00pm

[0066] Carbaporphyrins and Beyond: The Quest for Quatyrin
Limited Capacity seats available

Carbaporphyrins are porphyrin analogues where one of the interior nitrogens has been replaced by a carbon atom. In addition to true carbaporphyrins, which possess a cyclopentadiene unit, many related systems are known including N-confused porphyrins, benziporphyrins, azuliporphyrins and tropiporphyrins. These monocarbaporphyrinoid systems have unique reactivity and unusual spectroscopic properties. They range from fully aromatic macrocycles that resemble the porphyrins to nonaromatic systems, and indeed antiaromatic systems have also been noted. Many of these systems are superior organometallic ligands that form complexes with many late transition metal ions under mild conditions. For instance, azuliporphyrins have been reported to form stable complexes with Ni(II), Pd(II), Pt(II), Ir(III), Rh(III) and Ru(II). Carbaporphyrins also form organometallic derivatives with Ag(III), Au(III) and Pd(II). Given the unique and insightful properties exhibited by monocarbaporphyrinoid systems, syntheses of dicarbaporphyrinoids and further heterocycle-diminished species have been investigated. In these studies, porphyrinoid systems with two pyrrolic units and two carbocyclic moieties have been prepared. These include structures with two azulenes, two indenes, two cyclopentadiene rings, two benzenes, mixed benzene and azulene structures, and mixed indene and azulene macrocrocycles. These systems again demonstrate a wide range of aromatic properties and in some cases afford organometallic derivatives. The extent of aromatic character in these structures provides insights into the origins of aromaticity in the porphyrins. It is noteworthy that while some of these porphyrinoids retain highly diatropic characteristics, the stability of many dicarbaporphyrinoids in reduced compared to monoporphyrinoid systems. Hence, the pyrrole units in porphyrin appear to play an important role in stabilizing these macrocycles. Nevertheless, this work may lead to the development of synthetic routes to quatyrins, theoretically important hydrocarbon analogues of the porphyrins.

Invited Lecturers
avatar for Timothy D. Lash

Timothy D. Lash

Distinguished Professor of Chemistry, Illinois State University
Education: University of Exeter (United Kingdom): B.Sc. (Hon.), Chemistry, 1975. | University of Wales, College of Cardiff (UK): Ph.D. (Organic Chemistry), 1979.


Thursday August 27, 2015 2:00pm - 2:40pm
Corwin East

2:00pm

[0192] Developing a Library of Heterocycles to Fight Neglected Diseases
Limited Capacity seats available

The available drug space for treating neglected diseases are limited and do not cover desirable drug-like properties. The most recent trends in neglected diseases drug discovery aim to change this picture. In order to succeed advancing medicinal chemistry in the area, a good library of structurally diverse compounds covering the property-space for drug-likeness plays a central role. This talk will present our work on building library of heterocycles, based on five main strategies: innovative scaffolds, heterocyclic reactivity, heterocyclic fragment embedment, diversity oriented synthesis and total synthesis

Invited Lecturers
avatar for Flavio Emery

Flavio Emery

Associate Professor of Pharmaceutical Sciences, University of Sao Paulo
Pharmacist from the Federal University of Rio de Janeiro (UFRJ, 1998), obtained the title of Doctor of Natural Products Chemistry in 2005 at the Center for Natural Products Research (NPPN-UFRJ), under the guidance of the late Prof. Antonio Ventura Pinto, during which studied the synthesis and chemical reactivity of natural naphthoquinones. He is currently professor and researcher at the Faculty of Pharmaceutical Sciences of Ribeirão Preto... Read More →


Thursday August 27, 2015 2:00pm - 2:40pm
UCEN Flying A

2:00pm

[0193] Total Synthesis and Stereochemistry of (+)-Dragmacidin D
Limited Capacity seats available

Dragmacidin D is a complex deep-sea marine heterocyclic natural product whose stereochemical identity has remained unclear since its isolation. This bis(indole) pyrazinone alkaloid contains a single stereocenter, whose configuration was proposed based on stereochemistry of another congener, dragmacidin F. Recently, Capon and Jia revised the assignment to 6’’’R based on total synthesis, the first enantioselective preparation of dragmacidin D in 26 steps. We developed an effective direct asymmetric alkylation of arylacetic acids, which enabled the synthesis of (+)-dragmacidin D in 10 steps. Curiously, our own effort confirmed the originally proposed assignment as 6’’’S. We also determined that dragmacidin D undergoes a slow racemization in aqueous solution at pH 6.8, essentially complete within 16 days at room temperature.


Invited Lecturers
avatar for Armen Zakarian

Armen Zakarian

Professor of Chemistry, University of California, Santa Barbara
Armen Zakarian grew up in Moscow, where his scientific interests in chemistry were seeded by a rare opportunity to participate in a research group at the Zelinski Institute of Organic Chemistry during high school and later as an undergraduate student at Moscow State University. The research activities in the Kochetkov laboratories at the Zelinski Institute involved carbohydrate chemistry, and early mentorship was provided by Dr. Vladimir... Read More →


Thursday August 27, 2015 2:00pm - 2:40pm
Corwin West

2:00pm

[0196] Old Methods to New Targets: Accessing Highly Functionalized Heterocycles for Drug Development
Limited Capacity seats available

The development of a practical and efficient synthesis of an investigational drug candidate will be described.  A Vilsmeier-Haak quinolinone synthesis was first developed to support the initial multi-kilo manufactures.  Alternative chemistry based on a highly selective Friedlander cyclization was later discovered to provide efficient access to the key quinolinone intermediate. Development of subsequent transformations to access the target molecule including development of a  challenging Negishi coupling and selective oxime hydrogenation will also be described.  The process development ultimately provided access to the non-racemic drug candidate in 5-step chiral process with a 47% overall yield

Invited Lecturers
avatar for Christopher Borths

Christopher Borths

Senior Scientist, Amgen
Senior ScientistAmgenMarch 2010 – Present (5 years 1 month)ScientistAmgenAugust 2004 – March 2010 (5 years 8 months)EducationCaltech  Ph.D., Chemistry  2000 – 2004University of California, Berkeley  M.S., Chemistry  1998 – 2000University of Kentucky  B.S., Chemistry & Biology  1994 – 1998


Thursday August 27, 2015 2:00pm - 2:40pm
MCC Theater

2:40pm

[0002] Mangrolide A – A Novel Marine-Derived Antibiotic with Activity Against Gram-Negative Pathogens
Limited Capacity seats available

I will present results related to a structurally novel antibiotic termed Mangrolide A, which was isolated from a marine actinomycete from the mangrove swamps in the Bahamas. Structurally, mangrolide A shares similarity to fidaxomicin (®Dificid), which is a clinically approved narrow-spectrum antibiotic used for the treatment of the Gram-positive pathogen Clostridium dificile. However, Mangrolide A exhibits potent and selective bactericidal activity against Gram-negative pathogens, including those associated with cystic fibrosis and hospital-acquired pneumonia infections. Mechanism of action studies revealed that Mangrolide interferes with the ribosomal proofreading process, leading to an increased rate of error in protein synthesis. This is the first example of a macrolide glycoside structure displaying the mechanism of action found for aminoglycosides. The frequency of antibiotic-resistant bacteria is currently rising at an alarming rate; therefore, the need to identify new antibiotics has reached a critical level. It is estimated that greater than 1.7 million hospital-acquired bacterial infections occurred in 2008 (4.5 per 1000 patients), resulting in more than 100,000 deaths. The estimated costs on the U.S. health care budget attributed to these infections are $5 billion annually. Clinicians are increasingly concerned about the threat of Gram-negative pathogens, such as Pseudomonas aeruginosa, Acinetobacter baumanii and the Enterobacteriacaeae, the main causes of hospital-acquired pneumonia. In a recent CDC survey 26% of P. aeruginosa isolates and 37% of A. baumanii hospital-isolates were resistant to the most common antibiotic treatments. While there have been a few approved clinical candidates for Gram-positive pathogens, new treatments for Gram-negative pathogens have stalled in recent decades. Thus, the need for antibiotics that are effective against Gram-negative infections has become a medical necessity.

Invited Lecturers
avatar for Jef De Brabander

Jef De Brabander

Professor, The University of Texas Southwestern Medical Center


Thursday August 27, 2015 2:40pm - 3:20pm
Corwin West

2:40pm

[0073] Polysubstituted Pyrimidines: Biological and Chemical properties
Limited Capacity seats available

The pyrimidine ring represents an important pharmacophor and a key structural motif of numerous natural, as well as synthetic biologically active compounds. Various polysubstituted pyrimidines were studied in our team for their interesting and miscellaneous properties, namely antiviral (as non-nucleoside reverse transcriptase inhibitors), anticancer (as inhibitors of cyclin-dependent kinases), and anti-inflammatory (as inhibitors of nitric oxide and/or prostaglandin E2 production).

Some derivatives, e.g. polysubstituted 5-nitrosopyrimidines, were studied for their ability to form strong intramolecular hydrogen bonds. Such compounds were suggested to structurally (and hopefully also biologically) mimic bicyclic heterocycles like purines or pteridines.

Two possible rotamers were often observed depending on other substituents attached to the pyrimidine moiety and in several cases, they could even be isolated as chemical species.


Invited Lecturers
avatar for Zlatko Janeba

Zlatko Janeba

Head of the Team, Institute of Organic Chemistry and Biochemistry AS CR, v.v.i
Education | 1995-2001 | Ph.D. (CSc.) in organic chemistry, under supervision Prof. A. Holý, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague. | 1989-1995 | M.Sc. in organic chemistry, under supervision of Prof. A. Holý, Department of Organic Chemistry, Faculty of Chemical Technology, Institute of Chemical Technology, Prague.  | Experience | 2005-2008 (3 years)Moravek... Read More →


Thursday August 27, 2015 2:40pm - 3:20pm
UCEN Flying A

2:40pm

[0194] Synthesis and Up-Scaling of Finerenone, a Novel Potent and Selective Oral Non-Steroidal Mineralo-Corticoid Receptor (MR) Antagonist
Limited Capacity seats available

Finerenone (BAY 94-8862) is a novel potent and selective oral non-steroidal mineralo-corticoid receptor (MR) antagonist blocking deleterious effects of aldosterone. Increased activation of the MR leads to pathological changes in the heart and kidneys, which can be prevented by effective MR antagonism. Finerenone has demonstrated a promising efficacy and safety profile in preclinical studies as well as in Phase IIa. The MR antagonist is currently in clinical Phase IIb development for the treatment of worsening chronic heart failure and diabetic nephropathy and is expected to enter clinical Phase III end of 2015. Synthesis and up-scaling of the novel optical active Dihydropyridine derivative to commercial scale, as well as challenges during process development will be discussed. Application of SMB technique for separation of enantiomers on large scale will be demonstrated. Additionally, the synthesis and characterization of metabolites will be presented.


Invited Lecturers
avatar for Johannes Platzek

Johannes Platzek

Bayer Healthcare


Thursday August 27, 2015 2:40pm - 3:20pm
MCC Theater

2:40pm

[0206] "Life is Heterocyclic" (Metalation)
Limited Capacity seats available

The common theme in our laboratories is the invention and development of new DoM aromatic chemistry, separate and linked to transition metal catalyzed processes, and their demonstration in bioactive molecule, natural product, and materials construction. In honour of Alan Katritzky, a selection of these themes bearing on heterocyclic chemistry,
including new departures into DMG Dancing and Ir and Ru catalyzed DoM-enhancing
Connections, will be described.


Invited Lecturers
avatar for Victor A. Snieckus

Victor A. Snieckus

Professor of Chemistry, Queen's University
Research Interest •  Development of New Synthetic Methodology | •  Application of Directed ortho Metalation (DoM) for the Synthesis of Complex Aromatic and Heteroaromatic Molecules | •  Transition Metal Catalyzed Cross-Coupling Reactions | •  Synthesis of Natural Products and Bioactive Molecules | •  Collaborative projects with pharmaceutical industry in fundamental heterocyclic chemistry and... Read More →


Thursday August 27, 2015 2:40pm - 3:20pm
Corwin East

3:20pm

Coffee Break
Limited Capacity seats available

Thursday August 27, 2015 3:20pm - 3:40pm
UCEN Lagoon Plaza

3:40pm

[0006] Towards the Total Synthesis of the Tetranortriterpene Gedunin
Limited Capacity seats available

Gedunin (1), which was first isolated from the West African timber Entandrophragma angolense in 1960, has been reported to exhibit a diverse range of biological activities, including antimalarial, antifungal, allergic response, peptic ulcer, anti-cancer, eryptosis, antifilarial, and insecticidal activity. In terms of anticancer activity, however, gedunin (1) was explored through the use of a connectivity map, and found to exhibited antiproliferative activity through the heat shock protein Hsp90. Such compelling biological interest in this compound inspired our group to investigate a synthetic route to gedunin so as to open opportunities for better understanding the underlying biochemical pathways. The lecture will describe our efforts in achieving the construction of a key advanced intermediate and subsequent activities towards total synthesis

ST Lecturers
avatar for Craig Willams

Craig Willams

Assoc. Profrofessor, University of Queensland
Professor | University of Queensland



Thursday August 27, 2015 3:40pm - 4:00pm
Corwin East

3:40pm

[0010] Deprotonated α-Aminonitriles as versatile Building Blocks for the construction of N-Heterocycles
Limited Capacity seats available

The strong anion stabilizing capacity of the nitrile group permits a-aminonitriles with a primary or secondary amino group to be used as readily available a-aminocarbanion equivalents after deprotonation with a suitable base. These agents are versatile building blocks for the construction of highly substituted amines and N-heterocycles which can be obtained in very short reaction sequences or one-pot procedures. The related rearrangements of nitrile-stabilized ammonium ylides allow ring transformations such as the construction of protoberberine alkaloids in a single step.


ST Lecturers
avatar for Till Opatz

Till Opatz

Full Professor, Johannes Gutenberg-University
Till Opatz studied chemistry at the University of Frankfurt/M., Germany. He received his diploma under the guidance of Prof. Johann Mulzer in 1997. From 1997 to 2001, he worked on his Ph.D. thesis on glucose as a pentavalent scaffold for combinatorial chemistry in the group of Prof. Horst Kunz at the University of Mainz. He then joined the group Prof. Rob M. J. Liskamp at the University of Utrecht, The Netherlands, as a postdoc fellow studying... Read More →



Thursday August 27, 2015 3:40pm - 4:00pm
UCEN Lobero

3:40pm

[0014] Hantzsch-type Reaction of β-Formyl-β-nitroenamine: Multi-component Synthesis of 4-Substituted-3,5-dinitro-1,4-dihydropyridine
Limited Capacity seats available

1,4-Dihydropyridine (DHP) derivatives have attracted a considerable attention in medicinal chemistry and pharmacology due to the wide range of bioactivities, among which 4-arylated DHPs are also often found as the fundamental framework in drugs such as calcium antagonists and cardiovascular diseases.

On the other hand, we recently reported the novel method for construction of 4-arylated 3,5-dinitro-1,4-DHPs from β-formyl-β-nitroenamine as a reactive building block. Although this reaction serves as dinitro-DHPs that are not easily prepared by other method, the scope of the substrate is limited to highly electron-rich aromatics, and the theoretical maximum yield should be below 67%.

In this context, we have improved this reaction by using the strategy of Hantzsch-type multi-component reaction. Namely, a relevant multi-component reaction between two molecules of β-formyl-β-nitroenamine and an aldehyde is designed (Scheme), and we have succeeded to prepare various kinds of 4-aryl and 4-alkyl-3,5-dinitro-1,4-DHPs in high yields.

ST Lecturers
avatar for Haruyasu Asahara

Haruyasu Asahara

Kochi University of Technology | Kami/Kochi | Japan



Thursday August 27, 2015 3:40pm - 4:00pm
UCEN State

3:40pm

[0055] N-methylmelamines as precursors for new polymers
Limited Capacity seats available

Methylated melamines are widely used as anti-tumor drugs, insect sterilants, and as monomers for modified melamine-formaldehyde-polymers. Hydroxymethyl(methylmelamines) are metabolites of antitumor agents such as altretamine (hexamethylmelamine) and trimelamol trimethylol(trimethylmelamine)), formed by oxidation of a methyl group and subsequent elimination of formaldehyde. N-vinylmelamine derivatives offer a broad range of industrial applications, not only homopolymerization but also copolymerization with other monomers currently being under investigation. Our recent studies have used methylmelamines as building blocks for the synthesis of functional acrylyate monomers for coatings or in the synthesis of polymer additives.

 In attempt to produce new melamine polymers we have prepared different functional triazine compounds for further vinylation and then polymerization. The vinylgroup is usually attached to a free NH-group – the influence of different substituents on the Nitrogen on the rate of vinylation has been investigated and found to be of great importance. All substances were produced by a single-, two- or three step synthesis using cyanuric chloride as starting material. The products were analyzed with GC, mass spectrometry, and NMR and thus full structural elucidation achieved.

At the moment copolymerization of the vinyl melamines with commercially available monomers, such as ethylene, styrene, or methylmethacrylate is being done. Depending on the selected melamine derivative basic polymerization parameters such as catalysts, concentration of reactants, temperature, solvent and reaction time have been studied and optimized.

In order to characterize these new polymer products different analytical approaches were applied. The nitrogen content, as a measure of melamine incorporation, was determined with elemental analysis (CHN). But as this method does not give structural information on the molecular level, we also have used methods such as FTIR, NMR, analytical pyrolysis, or MALDI mass spectrometry for the characterization of our copolymers.


ST Lecturers
avatar for Manuela List

Manuela List

Postdoc, Johannes Kepler University Linz
Postdoc/ Johannes Kepler University Linz Austria



Thursday August 27, 2015 3:40pm - 4:00pm
Girvetz 2116

3:40pm

[0065] Biomimetic Synthesis of Phenylethanoid Alkaloids
Limited Capacity seats available

The phenylethanoids are a diverse group of shikimic acid derived natural products, characterised by the presence of a C6C­2 moiety.  These compounds are of great interest for their structural complexity and wide range of biological functions. Incargranine B is a dimeric phenylethanoid alkaloid, originally assigned an unprecedented indolo[1.7]naphthyridine structure. As a result of biosynthetic speculation, we proposed a dipyrroloquinoline core as a plausible alternative structure.  Following a biomimetic strategy, the proposed structure of incargranine B was accessed in six steps, confirming the suggested structural revision and indicating the natural product likely exists as a mixture of two pseudo-enantiomeric diastereomers. Extending upon this biomimetic synthesis, we now propose a unified biosynthetic hypothesis for the entire family of phenylethanoid natural products isolated from plants of the genus incarvillea. Studies towards the biomimetic synthesis of millingtonine and incargranine A will also be presented.


ST Lecturers
avatar for Patrick Brown

Patrick Brown

PhD Candidate, University of Edinburgh
Graduate Student | University of Edinburgh



Thursday August 27, 2015 3:40pm - 4:00pm
Girvetz 2119

3:40pm

[0090] Asymmetric Synthesis of Poison Dart Frog Indolizidine Alkaloids
Limited Capacity seats available

5-Substituted, 3,5-disubstituted, 5,8-disubstituted and 5,6,8-trisubstituted indolizidines belong to a group of alkaloids separated from the skin of poison dart frogs which lived in the tropical rainforest of Central and South America.  Some of these indolizidines have shown interesting AChEI activity which is important for the development of new drugs.

A series of substituted indolizidines, including 167B, 195G, 209B, 209D, 209I, 223A, 223AB, synthesized starting from tricyclic lactones will be discussed.  Key steps involved : 1) [3,3]-sigmatropic rearrangement to form tricyclic compounds with needed R1 substituent, 2) asymmetric alkylation/epimerization to obtain R2, 3) cyclization to form C7-C8 bond with R3 in correct stereochemistry, 4) construction of R4 (223AB case only), and 5) cleavage of the excess one carbon substituent on C5

ST Lecturers
avatar for Yu-Jang Li

Yu-Jang Li

Professor, National Chiayi University, Department of Applied Chemistry
Professor Department of Applied ChemistryNational Chiayi UniversityTaiwan 



Thursday August 27, 2015 3:40pm - 4:00pm
Corwin West

3:40pm

[0138] A Straightforward Access to the Chiral Cyclopentadienes via Intramolecular Metal Carbene/Carbenoid Cascade Transformations
Limited Capacity seats available

    Intramolecular metal carbene cascade reactions are effective and convenient access to construct functionalized cyclic frameworks. In this context, pioneering work was reported by Padwa,1 and multi-substituted furane derivatives synthesis is the focus via the carbonyl ylide intermediate at that age.2 Meanwhile, detailed mechanism study was carried out by Hoye and co-workers.3 Recently, this strategy has been applied to the synthesis of various cyclic frameworks via ending with two kinds of traditional metal carbene reactions:4 X-H insertion5 and cyclopropanation.6 Moreover, Doyle and co-workers have found that cycloaddition reactions could occur with cyclopropene intermediate in the presence of a compatible metal catalyst.7 Inspired by these works, we designed a intramolecular metal carbene cascade reactions, which is initiated from a metal carbene species generated from the corresponding diazo group, and terminated with an electronic rich alkenyl unite to form a cyclopentadiene derivatives with high to excellent enantioselectivity and high yields via cyclopropene intermediate (Scheme 1). To our best knowledge, although there are types of catalytic asymmetric metal carbene reactions disclosed, there is no asymmetric version reported in the metal carbene cascade reactions

ST Lecturers
avatar for Xinfang Xu

Xinfang Xu

Professor | Soochow University | Suzhou, Jiangsu



Thursday August 27, 2015 3:40pm - 4:00pm
UCEN Flying A

3:40pm

[0149] Catalytic One-Step Synthesis of Unprotected Piperazines, Morpholines and Thiomorpholines using SnAP Reagents
Limited Capacity seats available

Saturated N-heterocycles have long been considered as privileged elements for the preparation of bioactive small molecules. Increasing recognition of problems associated with aromatic pharmacophores, such as poor solubility, bioavailability, or pharmacokinetics have further enhanced their importance in drug development.[1] Despite this, their synthesis often have considerable limitations, including harsh reaction conditions, restricted substrate scope, long synthetic routes, and intractable protecting groups. To directly access a variety of saturated N-heterocycles in a single synthetic operation, we have recently introduced SnAP (Stannyl Amine Protocol) reagents, which convert aldehydes and ketones into (thio)morpholines, piperazines, diazepanes, spiro- and other N-heterocycles.[2–6]

The major limitation using the SnAP reagents is the need for stoichiometric copper reagents. We have now identified new ligands and conditions that render the reaction catalytic in copper and expanded the substrate scope including a-bis(substituted) SnAP reagents. These studies, including approaches towards an enantioselective process and insights into the unique reaction mechanism, will be discussed.

References:

1. N. A. Meanwell, Chem. Res. Toxicol. 2011, 24, 1420–1456.
2. C.-V. T. Vo, G. Mikutis, J. W. Bode, Angew. Chem. Int. Ed. 2013, 52, 1705–1708.
3. M. U. Luescher, C.-V. T. Vo, J. W. Bode, Org. Lett. 2014, 16, 1236–1239.
4. C.-V. T. Vo, M. U. Luescher, J. W. Bode, Nat. Chem. 2014, 6, 310–314.
5. W.-J. Siau, J. W. Bode, J. Am. Chem. Soc. 2015, 136, 17726–17729.
6. K. Geoghegan, J. W. Bode, Org. Lett. 2015, 17, 1934–1937.


ST Lecturers
avatar for Michael Umberto Luescher

Michael Umberto Luescher

Doctoral Student, ETH Zurich
Graduate Student Bode Group ETH Zurich - Switzerland



Thursday August 27, 2015 3:40pm - 4:00pm
UCEN Harbor

3:40pm

[0156] Enantioselective aza-Henry Reaction of Arylnitromethane using Homogeneous Brønsted Acid-Base Catalyst under Intermittent-Flow Conditions with a Recycle
Limited Capacity seats available

Growing knowledge in the area of continuous processing has established that flow methods could serve as an effective substitute to the majority of batch techniques providing unique advantages and straightforward solutions to the challenging chemical reactions. We have transformed a standard enantioselective batch aza-Henry reaction into intermittent-flow process. This novel platform produces valuable synthetic building blocks on a multigram scale with an increased overall intensity while addressing the common safety concerns associated with utilization of nitroalkanes. Organocatalyst was separated and continuously recycled providing reduced catalyst loadings. This project showcases successful synergy between efficiency of organocatalysis and transformative power of continuous processing. It also allows to effectively integrate green chemistry (reduced production footprint), atom economy (minimized reactor size, solvent volumes and application of catalyst recycle) and higher safety margins (decreased safety risks, defined operating space for nitroalkanes); overall these advantages lead to a significant cost benefit. The designed process could be utilized for a large scale synthesis of differentially protected diamines which are useful building blocks with a broad scope of applications.

ST Lecturers


Thursday August 27, 2015 3:40pm - 4:00pm
Girvetz 2115

3:40pm

[0189] C-H insertions in oxidative gold catalysis: Synthesis of bicyclic dihydropyran-3-ones from in situ generated α-oxo gold carbenes through the relay of vinyl cation intermediates
Limited Capacity seats available

An expedient synthesis of bicyclic dihydropyran-3-one compounds is realized in a cascade trigged by oxidative gold catalysis. In this reaction, the initially formed α-oxo gold carbene intermediate, generated upon gold-catalyzed oxidation of alkyne, could be trapped by a tethered C-C triple bond, thereby generating a vinyl cation intermediate. This intermediate of highly electrophilicity is likely responsible for the intramolecular concerted C-H insertion. The reaction provides a simple way of constructing functionalized bicyclic system from easily accessible propargyl ethers.


ST Lecturers
avatar for Zhitong Zheng

Zhitong Zheng

Graduate Student | Zhang Group | UCSB Chemistry | Santa Barbara California



Thursday August 27, 2015 3:40pm - 4:00pm
Girvetz 2112

4:00pm

[0003] Total Synthesis and Structural Revision of Muironolide A
Limited Capacity seats available

Muironolide A is a fascinating tetrachlorinated marine polyketide isolated from the sponge of Phorbas sp. Only 90 mg had been isolated, and the structure was established by nanoscale NMR techniques. Herein we report the total synthesis of the substance with the assigned structure of muironolide A, propose a revised structure based on NMR data, and complete the enantioselective total synthesis of muironolide A.


ST Lecturers
avatar for Kyle Young

Kyle Young

Graduate Student (Zakarian), University of California, Santa Barbara
NSF Predoctoral Fellow | Zakarian Group | UCSB Department of Chemistry | Santa Barbara, California, USA |  



Thursday August 27, 2015 4:00pm - 4:20pm
UCEN Harbor

4:00pm

[0009] Scale Up of Azaindole Compound: A Story of Synthetic Evolution
Limited Capacity seats available

Azaindole compound is a potent inhibitor of influenza, and has complex structure which is a challenge for scale up. We use enzymatic desymmetrization of 1,3-bisester-cyclohexane to generate the two chiral centers with high yield (99%) and high ee (99%). The first generation of synthesis employs the displacement of chiral monoBoc-diaminocyclohexane with sulfoxide, followed by urea formation (10 steps); The second generation of synthesis is racemic and need SFC separation (6 steps); The third generation of synthesis employs a Curtius rearrangement of acid to install morpholin urea in one step (7 total steps with 33% overall yield). All steps from last route are high yielding and easy to scale up.


ST Lecturers
avatar for Colin Liang

Colin Liang

Sr Research Scientist, Vertex Pharmaceuticals
Sr Research Scientist | Vertex Pharmaceuticals



Thursday August 27, 2015 4:00pm - 4:20pm
MCC Theater

4:00pm

[0032] Exploration of New Synthetic Methodologies for the Synthesis of Heterocyclic Scaffolds
Limited Capacity seats available

Heterocyclic compounds are an important class of chemical compounds and are present in wide variety of drugs, photo-luminescent substances, agrochemical products, natural products etc.; thus play vital role in medicine, industry and life1. Recent upsurge in the field of synthetic organic chemistry has brought into light many techniques, such as C-H activation,2 transition metal-catalysed cross coupling reactions, multicomponent reactions3 etc., which expanded the horizons in the field of heterocycles, a feat that was never envisaged before. The main aim of our research is to focus our attention on the application of these methodologies for the construction of diversified and complex heterocyclic molecules. Recently, we published Ruthenium catalyzed C-H activation of the nitrogen containing heterocycles, wherein the innate reactivity of the heterocycle can be exploited for regioselective demonstrated C-2’ alkenylation of 2-phenylimidazo[1,2-a]pyridine (Scheme 1A).4 Presently we are exploring synthesis of 2-aminobenzothiazoles from N-phenyl thiouresa by palladium catalysed C-H functionalization/ C-S bond formation (Scheme1B).  Salient features and mechanistic aspects will be presented.


ST Lecturers
avatar for R T Pardasani

R T Pardasani

Professor | Central University of Rajasthan



Thursday August 27, 2015 4:00pm - 4:20pm
UCEN State

4:00pm

[0033] Heterocycle Synthesis from Quinols
Limited Capacity seats available

A variety of substituted 1-hydroxyacridones were synthesized in a one-pot carbamation/Michael addition/Claisen Condensation/decarboxylation cascade in two steps from commercial phenols in good to excellent yields (41-96%). Furthermore, synthesis of 4-hydoxycarbazoles from quinols was realized through a carbamation/Michael/enolate-aryl coupling/aromatization sequence. This methodology was also applied to a short total synthesis of carbazomycin B.


ST Lecturers
avatar for Jing Wu

Jing Wu

Graduate Student, | Hunter College, | New York, NY



Thursday August 27, 2015 4:00pm - 4:20pm
Girvetz 2112

4:00pm

[0072] Talkative Molecules: Design and Synthesis of Functional Bodipy Compoundss
Limited Capacity seats available

Among many dipyrrin complexes the difluoro-boraindacene family (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene, Bodipy) has gained recognition as one of the more versatile fluorophores since it has emerged as a frontrunner for lasing, imaging, sensing and opto-electronic applications. The basic Bodipy unit can be readily functionalized and shift the absorption maxima over a wide spectral range. The major objective of our study is to develop Bodipy-based functional materials for various applications such as photostable laser dyes, Bodipy based organoelectronic materials and photosensitizer for Photo-Dynamic Therapy (PDT). This warrants synthetic modifications of the Bodipy core, available commercially or synthesized in-house so as to impart the desirable attributes to the newly developed molecules/assemblies. To this end, various sites of the Bodipy cores viz. different positions of the dipyrrole moieties and/ or the meso-position are innovatively used for introduction of different functional groups. Several new Bodipy-O-glycosides were synthesized by incorporating the glucose unit at meso-phenol or C-3/C-5 hydrostyryl moieties. Subsequent attachment of a glucose unit to the phenolic function of the conjugated dyes furnished the photosensitizers. All the compounds showed impressive good photo-toxicity to the human lung cancer A549 cells, without any dark toxicity due to their accumulation in cytoplasm. The efficacy of the protocols in designing new molecules and the potential functional applications along with their biomedical usefulness will be emphasized in the talk. 

ST Lecturers
avatar for Neelam Shivran

Neelam Shivran

Postdoctoral Fellow, IISER Pune
Indian Institute of Science Education and ResearchPune India



Thursday August 27, 2015 4:00pm - 4:20pm
Girvetz 2116

4:00pm

[0086] The Total Synthesis of Gelsenicine via Platinum-Catalyzed Cycloisomerization
Limited Capacity seats available

The Gelsemium alkaloids constitute a significant family of natural products featuring a breadth of both structural and biological diversity.  Our efforts toward a unified total synthesis of these molecules will be presented.  A focal point of this endeavor is the application of a cascade platinum-catalyzed cycloisomerization/rearrangement to establish the core molecular architecture of these alkaloids.  Our analysis of this specific transformation provided a fundamental understanding of this unique process and the facets that govern it.  Our studies of this central process and subsequent direct manipulations have culminated in the successful total synthesis of gelsenicine, representing the shortest total synthesis to date of a Gelsemium alkaloid.  We envision strategic diversifications will enable the syntheses of a broad array of members in the gelsemium family.  Our overall efforts in this project will be presented.


ST Lecturers
avatar for Eric Ferreira

Eric Ferreira

Associate Professor, University of Georgia
Associate Professor | University of Georgia | Athens, GA 30602



Thursday August 27, 2015 4:00pm - 4:20pm
Corwin West

4:00pm

[0109] Cross-dehydrogenative C-H Bond Silylation of Aromatic Heterocycles by an Earth-abundant Metal Catalyst
Limited Capacity seats available

Arylsilanes are of great interest in the fields of organic electronics and photonics, medicinal chemistry, and complex molecule synthesis due to the unique physicochemical features of the aromatic carbon-silicon (C–Si) bond.

We have recently discovered a mild and regioselective C–H bond functionalization of aromatic heterocycles catalysed by a plentiful and inexpensive Earth-abundant metal salt [1]. The method enables the direct silylation of heteroaryl C(sp2)–H bonds that both obviates the need for expensive precious metal catalysts and overcomes various limitations of previous methods. Applications to materials science and to the late-stage derivatization of pharmaceutical substances will be presented.


ST Lecturers
avatar for Anton Toutov

Anton Toutov

PhD Candidate; Grubbs Laboratory, Caltech
PhD Candidate at California Institute of Technology. NSERC Predoctoral Fellow. Dow-Resnick Predoctoral Fellow.



Thursday August 27, 2015 4:00pm - 4:20pm
UCEN Flying A

4:00pm

[0114] Structural Modifications of Quinoidal Molecules towards Bioactive and Fluorescent Heterocycles
Limited Capacity seats available

Over the past five years, our group has employed in design, synthesis and optimization of new heterocyclic compounds with different biological applications.1,3 In this context, we revealed the synthesis and the biological evaluations (e.g. bioimaging, cellular uptake and dynamics in living cells) of some new fluorescent oxazoles and their boron complexes which have allowed for selectively visualizing the whole endocytic pathway. The target compounds were characterized by spectroscopic analyses, single crystal X-ray, photophysics and DFT calculations. In addition, a straightforward synthesis of chalcogen-containing β-lapachones with trypanocidal and antitumor activities and a new probe for alkaline metals are also described from lapachol, an affordable naturally occurring naphthoquinone

ST Lecturers
avatar for Eufrânio da Silva Júnior

Eufrânio da Silva Júnior

Eufrânio N. da Silva Júnior received his degree in chemistry from the Catholic University of Brasília (UCB). In 2007, he completed his MSc at the Fluminense Federal University (UFF) and in 2009 he concluded his PhD at the University of Brasilia (UnB). In 2010, he became Professor of Chemistry at the Federal University of Minas Gerais (UFMG). His research interests are focused on click chemistry reactions, mechanism... Read More →



Thursday August 27, 2015 4:00pm - 4:20pm
Girvetz 2115

4:00pm

[0150] Pyrazoloquinazolinones and benzimidazoquinazolinones via a 3 + 3 N-acylation-SNAr strategy
Limited Capacity seats available

An efficient synthesis of pyrazolo[1,5-a]quinazolin-5(4H)-ones and pyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-5(4H)-ones is reported from the reaction of 2-haloaroyl chlorides with 5-amino-1H-pyrazoles.   A similar preparation of benzo[4,5]imidazo[1,2-a]quinazolin-5(6H)-ones and benzo-[4,5]imidazo[1,2-a]pyrido[3,2-e]pyrimidin-5(6H)-ones results from the reaction of 2-haloaroyl chlorides with 2-aminobenzimidazoles.  These syntheses take advantage of the 1,3-disposition of electrophilic centers in the acid chloride and a similar arrangement of nucleophilic sites in 5-amino-1H-pyrazole and 2-aminobenzimidazole to form the central six-membered ring by a 3 + 3 strategy.  Initial acylation of the amino group of the pyrazole or benzimidazole occurs in DMF containing carbonate base at –10 oC.  Subsequent heating, in the same reaction vessel, completes the synthesis via an SNAr ring closure between N1 of the pyrazole or benzimidazole and the 2-haloarylamide. The reaction gives 66–93% yields for the two-step sequence.  These compounds are known to intercalate into DNA, and thus, may be useful as antiproliferative agents for cancer treatment.  Mechanistic and spectral aspects of the project will also be presented.


ST Lecturers
avatar for Richard A. Bunce

Richard A. Bunce

Professor of Chemistry | 107 Physical Sciences 1



Thursday August 27, 2015 4:00pm - 4:20pm
Corwin East

4:00pm

[0217] Synthesis and Conformational Studies of Small Molecule Macrocyclic Inhibitors of ALK/ROS1 – Discovery of PF-06463922
Limited Capacity seats available

This talk will focus on the synthesis of the chemical properties of the macrocyclic inhibitors developed for the EML4 ALK program for the treatment of NSCLC leading to the discovery of the clinical candidate PF-06463922. The work disclosed will feature (i) variations of the heterocyclic tailpiece of the molecule, and the synthetic chemistry to incorporate these into the macrocyclic ring through either macrolactamization or direct arylation, (ii) conformational studies and atropisomerism of specific macrocyclic ring systems, and (iii) optimization and scale-up of the clinical candidate including the evolution of the synthesis of the pyrazole tailpiece.


ST Lecturers
avatar for Paul Richardson

Paul Richardson

Pfizer
Senior Principal Scientist, Pfizer, La Jolla



Thursday August 27, 2015 4:00pm - 4:20pm
Girvetz 2119

4:20pm

Walkabout
Find your way back to invited talks and perhaps switch rooms

Thursday August 27, 2015 4:20pm - 4:40pm
TBA

4:40pm

[0044] Functional Heterocyclic π-Systems by Multicomponent and Domino Syntheses
Limited Capacity seats available

Multi-component and domino reactions are efficient and effective methods in the rapid and diversity-oriented synthesis of heterocycles. In particular, transition metal catalyzed multi-component sequences have recently gained a considerable interest.1 Based upon transition metal catalyzed entries to ynones, diynones, and enones and sequentially Pd-catalyzed processes we have opened new avenues to one-pot syntheses of numerous classes of heterocyclic frameworks.2 Among functional p-electron systems3 selected luminescent heterocycles are readily accessible in a modular fashion. They display peculiar photophysical properties, such aggregation induced emission,4 pronounced emission solvochromicity, and photoinduced charge separation in DSSC.

Invited Lecturers
avatar for Thomas J. J. Müller

Thomas J. J. Müller

Professor, Heinrich-Heine-University Düsseldorf


Thursday August 27, 2015 4:40pm - 5:20pm
Corwin West

4:40pm

[0093] Synthesis of a Heterocyclic Pharmaceutical Intermediate via an Intramolecular Asymmetric [3+2] Nitrone/Olefin Cycloaddition
Limited Capacity seats available

 

A scalable, asymmetric synthesis of (3aS,6aS)-6a-(5-bromo-2-fluorophenyl)-1-((R)-1-phenylpropyl)tetrahydro-1H,3H-furo[3,4-c]isoxazole (1), a key intermediate in the synthesis of LY2886721 is reported.  Highlights of the synthesis include: (1) The development of an asymmetric [3+2] intramolecular cycloaddition through a combined kinetic modeling and experimental approach; (2) The development of a new synthesis of (R)-N-(1-phenylpropyl)hydroxylamine tosylate (2) which proceeds through a p-anisaldehyde imine and avoids the formation of toxic hydrogen cyanide gas as a by-product.  Results of a synthesis executed on the multi-100 kg scale (which proceeded in 36% overall yield) will be discussed.


Invited Lecturers
avatar for Stan Kolis

Stan Kolis

Research Advisor, Small Molecule Design and Development, Eli Lilly and Company
Working in design and development of small molecule API Synthetic routes for transfer to commercial development. Led a group of chemists and engineers whose primary task was kinetic reaction modeling. Also have oversight for the Lilly Process Safety Lab.


Thursday August 27, 2015 4:40pm - 5:20pm
MCC Theater

4:40pm

[0207] Molecular Gymnastics: bond formation with rearrangements
Limited Capacity seats available

The turn of the century brought about a pressing need for new, efficient and clean strategies for the chemical synthesis of biorelevant compounds. Our group has studied the use of various molecular rearrangements and atom-economical transformations as particularly appealing means towards the streamlined synthesis of complex small molecule targets.1,2,3

 

In this lecture, we will present an overview of our research in these areas and how they provide efficient solutions for total synthesis as well as platforms for the discovery of unusual reactivity.

 

References

[1] (a) Luparia, M.; Oliveira, M.T.; Audisio, D.; Frébault, F.; Maulide, N. Angew. Chem. Int. Ed. 2011, 50, 12631. (b) Audisio, D.; Luparia, M.; Oliveira, M.T.; Frébault, F.; Klütt, D.; Maulide, N. Angew. Chem. Int. Ed. 2012, 51, 7314. (c) Misale, A. ; Niyomchon, S. ; Luparia, M. ; Maulide, N. Angew. Chem. Int. Ed. 2014, 53, 7068.

[2] Huang, X.; Maulide, N. J. Am. Chem. Soc. 2013, 135, 7312.

[3] Jurberg, I.D.; Peng, B.; Wöstefeld, E.; Wasserloos, M.; Maulide, N. Angew. Chem. Int. Ed. 2012, 51, 1950.


Invited Lecturers
avatar for Nuno Maulide

Nuno Maulide

Professor of Chemistry, University of Vienna
| Full Professor of Organic Synthesis at the University of Vienna  (AT) | ERC Starting Grant holder. | Author Profile (Angewandte Chemie) (auf Deutsch) | | | 2013Habilitation (Venia Docendi) at the Ruhr-Universität Bochum (DE) | | 2009-2013Max-Planck-Research Group Leader (W2/Associate Professor, non-tenure-track) at the Max-Planck Institut für Kohlenforschung (DE) | | 2007-2008Postdoc at Stanford University... Read More →


Thursday August 27, 2015 4:40pm - 5:20pm
Corwin East

4:40pm

[0219] Gold catalysis in the synthesis of heterocycles
Limited Capacity seats available

Heterocycles are important structural motifs found in various natural products and functional materials. Their syntheses under mild reaction conditions and in highly efficient manners are still much in demand. On the other hand, Au catalysis has lately emerged as a powerful platform for the development of versatile synthetic methods.

 In this presentation, two general strategies for the synthesis of N-/O-heterocycles in the context of gold-catalyzed transformations of alkynes will be discussed. In the first strategy, oxidative catalysis using tethered or external nucleophilic oxidants provide rapid access to azetidin-3-ones, tetrahydrobenzazepinones, piperidin-4-ones, azepen-4-ones and other ring systems. In the second strategy, gold catalysis is employed as the ‘spring board’ to provide access to versatile intermediates otherwise difficult to obtain, and their further transformations/rearrangements enable the preparation of heterocycles. Among the various implementations of these strategies to be presented, three selected cases are outlined in the Scheme. Applications of these methods in natural product synthesis will also be discussed


Invited Lecturers
avatar for Liming Zhang

Liming Zhang

University of California at Santa Barbara


Thursday August 27, 2015 4:40pm - 5:20pm
UCEN Flying A

5:30pm

Goleta Beach BBQ
Limited Capacity seats available

Follow the trail along the bluffs that leads toward the airport, the pier and Goleta Beach. It's about a 20 min walk.   Our tables are in Lot 5.




Thursday August 27, 2015 5:30pm - 7:30pm
Goleta Beach
 
Friday, August 28
 

7:30am

Breakfast
Friday August 28, 2015 7:30am - 8:30am
Ortega Dining Commons

8:55am

Announcements
Limited Capacity seats available

Friday August 28, 2015 8:55am - 9:00am
Corwin Pavilion

9:00am

[0195] Toward a nature-inspired, dual-catalytic method to dehydrogenate organic compounds
Limited Capacity seats available

This lecture will describe our development of a light-induced, dual-catalytic method for converting saturated hydrocarbons to alkenes with the simultaneous formation of hydrogen gas.  This ‘dehydrogenation’ process uses two mutually compatible, base metal catalysts to generate alkenes and molecular hydrogen by sequential carbon–hydrogen bond cleavages.  The sequential, catalyst-mediated hydrogen atom transfers occur at room temperature and call to mind the mechanism of nature’s desaturase enzymes.  In the wake of the alkene synthesis, the ‘hydrido’ forms of the catalysts undergo a reaction that liberates hydrogen gas and returns the catalysts to the reaction.  Our ongoing efforts to achieve diverse chemical reactions that are attended by dehydrogenations will also be addressed.


Plenaries and Awardees
avatar for Erik Sorensen

Erik Sorensen

Arthur Allan Patchett Professor in Organic Chemistry, Princeton University
Professor Sorensen was born and raised in upstate New York and received his B. A. degree in Chemistry from Syracuse University, where he performed undergraduate research with Professor Roger Hahn. In 1989, he began his graduate studies in chemical synthesis at the University of California, San Diego. Under the direction of Professor K. C. Nicolaou, he synthesized a novel family of DNA cleaving, 10-membered ring enediynes, contributed to a... Read More →



Friday August 28, 2015 9:00am - 10:00am
Corwin Pavilion

10:00am

[0201] Complex Natural Products as a Driving Force for Discovery in Organic Chemistry
Limited Capacity seats available

Our laboratory is deeply interested in the discovery and development of new reaction methodology en route to the chemical synthesis of complex bioactive molecules.  Research in our group at the California Institute of Technology is centered in the general area of synthetic chemistry, with a focus on the development of new strategies for the preparation of complex molecules, including natural products that possess interesting structural, biological, and physical properties.  Concurrent to this program of target driven synthesis is a strong effort directed toward the development of new techniques and reaction methods, which will be useful for a range of applications.  Typically, the complex target structure is used as an inspiration for the discovery of new reactions and technologies that may eventually be regarded as general synthetic methodology.  Consequently, this approach provides access to a) novel, medicinally relevant structures, b) a general method for their synthesis, and c) new synthetic methods that will be beneficial for a host of applications. 

                  The catalytic asymmetric synthesis of all-carbon quaternary stereocenters stands as a significant challenge in synthetic chemistry and we have encountered this problem many times in the course of natural product total syntheses.  As a result of such endeavors, we have been developing mild, catalytic methods that allow for efficient and stereoselective construction of these challenging centers.  Our recent results and applications of these new methods will be discussed in the lecture.

Plenaries and Awardees
avatar for Brian Stoltz

Brian Stoltz

Professor of Chemistry, California Institute of Technology
Degrees: | • B.S., Indiana University of Pennsylvania 1993 | • M.S., Yale University (John Wood), 1996 | • Ph.D., Yale University (John Wood), 1997 | • NIH Postdoctoral Fellow, Harvard University (E. J. Corey), 1998-2000 | Honors and Awards: | • Nankai University Lectureship, Nankai University, Tianjin, China, March 2012 | • R. C. Fuson Visiting Professorship, University of Illinois at Urbana-Champaign, Urbana, IL... Read More →



Friday August 28, 2015 10:00am - 11:00am
Corwin Pavilion

11:00am

Closing Remarks by Dan Comins & Oliver Reiser
Limited Capacity seats available

Friday August 28, 2015 11:00am - 11:20am
Corwin Pavilion

11:30am

Lunch
Friday August 28, 2015 11:30am - 12:30pm
Ortega Dining Commons