title: Andrastins A-C, new protein farnesyltransferase inhibitors 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.
authors.affiliation: Research Center for Biological Function, Kitasato Institute, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Uchida
authors.forename: K
authors.initials: K
authors.lastname: Shiomi
authors.forename: J
authors.initials: J
authors.lastname: Inokoshi
authors.forename: T
authors.initials: T
authors.lastname: Sunazuka
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Iwai
authors.forename: H
authors.initials: H
authors.lastname: Takayanagi
authors.forename: S
authors.initials: S
authors.lastname: Omura
mesh_terms: D019883:Alkyl and Aryl Transferases; D000730:Androstadienes / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D051231:Farnesyltranstransferase; D015394:Molecular Structure; D010407:Penicillium; D013329:Structure-Activity Relationship; D014166:Transferases / Q000037:antagonists & inhibitors*
chemical_list: D000730:Androstadienes; C100395:andrastin A; C100396:andrastin B; C100397:andrastin C; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase