ISHC2015

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.