Conformational Study of the Cembranoid Sarcophytol a, a Potent Anti-Tumor-Promoter

Abstract

Conformational analysis of the marine cembranoid sarcophytol A (la), 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 la, which afforded 7R,8R/7S,8S- and 11 R, 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 a-methoxy-a-trifluoromethylphenylacetate (lc) was carried out simultaneously. This confirmed the 14S absolute configuration of la but the conformation of crystalline lc did not correspond to any of the four minimum-energy conformers of la. © 1990, The Pharmaceutical Society of Japan. All rights reserved.