Conformational study of the cembranoid sarcophytol A, a potent anti-tumor-promoter.

Abstract

Conformational analysis of the marine cembranoid sarcophytol A (1a), a potent anti-tumor promoter, was carried out using a newly introduced molecular mechanic and molecular dynamic program Discover. Four minimum-energy conformations were derived, in accordance with a previous results of the epoxidation of 1a, which afforded 7R,8R/7S,8S- and 11R,12R/11S,12S-epoxide pairs. The most stable conformation was the one having C-19 and C-20 directed opposite to C-18, with respect to the average plane of the fourteen-membered ring. X-Ray crystallography of sarcophytol A alpha-methoxy-alpha-trifluoromethylphenylacetate (1c) was carried out simultaneously. This confirmed the 14S absolute configuration of 1a but the conformation of crystalline 1c did not correspond to any of the four minimum-energy conformers of 1a.