The cembrane diterpenes are a large class natural products that contain a 14-membered ring. Many members of the class - lobohedliolide, crassin, sinularin, dihydrosinularin, and others - show considerable anticancer activity, both in vivo and in vitro. In spite of this biological activity, relatively little synthetic work has been carried out in the field, probably because few methods of synthesis exist for preparing large-ring carbocycles. This proposal puts forward a plan for the synthesis of representative cembrenoids utilizing new methods developed in the P.I.'s laboratory for the synthesis of large-ring cycloalkenes, large-ring 1, 2-diols, and large-ring ketones. Specifically, plans are put forward for the total synthesis of isocembranolide, sinularin, and crassin. By preparing these compounds, these natural products and their analogs will become more readily available and chemical knowledge of reaction selectivity in large- ring carbocycles will be extended.
