Andrastins A-C, New Protein Farnesyltransferase Inbibitors Produced by Penicillium sp. FO-3929. II. Structure Elucidation and Biosynthesis.

Abstract

The structures of new protein farnesyltransferase inhibitors, andrastins A-C, were elucidated. The cyclopentane ring of andrastins exhibited keto-enol tautomerism, which made the structure hard to elucidate. Therefore, the structure of andrastin A was elucidated by INADEQUATE and 13C-13C couplings using 13C-labeled andrastin A. The absolute configuration of the p-bromobenzoyl derivative of andrastin A was elucidated by X-ray crystallographic analysis and its skeleton was shown to be ent-5 alpha,14 beta-androstane. The biosynthesis of andrastin A was also studied by the incorporation of 13C-labeled acetates. Though the andrastins had a common androstane skeleton, they were biosynthesized from a sesquiterpene and a tetraketide.