ANDRASTINS A-SIMILAR-TO-C, NEW-PROTEIN FARNESYLTRANSFERASE INHIBITORSPRODUCED BY PENICILLIUM SP FO-3929 .2. STRUCTURE ELUCIDATION AND BIOSYNTHESIS

The structures of new protein farnesyltransferase inhibitors, andrasti ns A similar to C, were elucidated. The cyclopentane ring of andrastin s exhibited keto-enol tautomerism, which made the structure hard to el ucidate. Therefore, the structure of andrastin A was elucidated by INA DEQUATE and C-13-C-13 couplings using C-13-labeled andrastin A. The ab solute configuration of the p-bromobenzoyl derivative of andrastin A w as elucidated by X-ray crystallographic analysis and its skeleton was shown to be ent-5 alpha,14 beta-androstane. The biosynthesis of andras tin A was also studied by the incorporation of C-13-labeled acetates. Though the andrastins had a common androstane skeleton, they were bios ynthesized from a sesquiterpene and a tetraketide.