STEREO- AND REGIOSELECTIVE SYNTHESIS OF TRICYCLIC SPIROLACTONES VIA DIASTEREOMERIC DIFFERENTIATION OF COLLECTIVE KEY PRECURSOR: ACCESS TO NATURAL AND UNEXPLORED FRAMES

Tricyclic spiranoid lactones can be frequently observed as scaffold segments of various biochemical compounds of natural origin. Analysis of their molecular frames reveals a compact carbon skeleton with angularly fused tricycles of different oxidation states in each of the rings, which together present a substantial synthetic challenge. We designed a general and collective synthesis of topologically diverse spiranoid lactones via controlled cyclizations of simple and easily accessible key precursors. Our synthetic strategy is short, regioselective, and offers the possibility to access a broad spectrum of quaternary carbon-centered spiranoid scaffolds.

The rapid composition of cycloalkylmethylene key precursors yields an assembly of bicyclic diastereomeric iodolactones, which are individually converted to form a wide range of tricyclic angularly fused spiranoid lactones of different topologies by simple diastereomeric differentiation in a regioselective and stereodirected fashion.

The synthetic advantage of novel protocol is exemplified by the successful preparation of tricyclic topologies of tricyclic spirafuranone frames via the shortest sequence reported to date and through the use of simple, easily accessible starting materials. Given the high degree of similarity of such scaffolds to natural compounds and the chemical diversity, that is now accessible by fast and simple synthetic routes, it is believed that such compounds may pave the way to the design, synthesis, and biological evaluation of new materials with potential drug-like activity.