The primary goal of the investigation is the development of an efficient method for the preparation of cadinane sesquiterpenes, which comprise a growing class of biologically-active natural products. Two different approaches, both of which employ a stereospecific beta-lactone rearrangement as the cornerstone transformation, will be examined, and their relative strengths assessed and compared. Each protocol will be investigated, first with model systems, and with particular attention to stereochemical control. The total synthesis of several naturally-occurring, butenolide-containing cadinanes will then be attempted, using appropriately designed starting molecules. The first route, although longer, offers the greatest potential for unequivocal stereochemical control. However, if the second route exhibits high stereoselectivity in the key beta-lactone-forming step, its considerable brevity will bode well for wide application. Both routes allow for asymmetric syntheses by using optically enriched starting materials. %%% With this award, the Organic Synthesis Program will support the research of Dr. T. Howard Black at Eastern Illinois University, which is an undergraduate institution. The research will apply the beta-lactone/gamma-lactone rearrangement of the synthesis of the cadinane class of sesquiterpenes. This should provide a stimulating introduction and training of undergraduate students in research, besides producing new syntheses of the challenging cadinane class of molecules.
