Andrastins A-C, new protein farnesyltransferase inhibitors produced by Penicillium sp. FO-3929. II. Structure elucidation and biosynthesis.
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.
Uchida
R
R
Research Center for Biological Function, Kitasato Institute, Tokyo, Japan.
Shiomi
K
K
Inokoshi
J
J
Sunazuka
T
T
Tanaka
H
H
Iwai
Y
Y
Takayanagi
H
H
Omura
S
S
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*
D000730:Androstadienes; C100395:andrastin A; C100396:andrastin B; C100397:andrastin C; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase