This proposal is directed toward the synthesis of cembranoid natural products derived from marine organisms, a class of compounds whose chemistry and biological activity have been little studied. The specific objectives, crassin acetate, sinularin, lobophytolide, and asperdiol, are cytotoxic and may exhibit antimicrobial, antiprotazoal, and cardiovascular activity. Crassin acetate has been found to cause respiratory failure in rats by direct action on the central nervous system. While the main theme is total synthesis, it is also planned to utilize relatively accessible natural cembranoids for chemical studies. Various regio and stereoselective transformations will be examined to gain insight regarding the basic chemical behavior of the more complex cembranoids. There is an acute need for such information as much of the structural work has involved spectroscopic and X-ray analysis rather than chemical degradation. Biological testing of synthetic intermediates and degradation products will be arranged with the appropriate NIH division.