Structure-activity relationships of virginiae butanolide C, an inducer of virginiamycin production in streptomyces virginiae

Abstract

Virginiae butanolide C, [2-(1′-hydroxyhexyl)-3-(hydroxymethyl)butanolide (3)], is one of the inducers of virginiamycin production in Streptomyces virginiae. Various racemic analogues were synthesized, and their effectiveness in virginiamycin induction was studied. Among analogues having a series of C-2 side chains, those with 1′-hydroxyheptyl or 1′-hydroxyoctyl moiety were most effective with a minimum effective concentration of 0.8 ng/ml. At the same length of C-2 side chain, a 2, 3-cis analogue was 10-fold more active than a 2, 3-trans analogue, and the 2, 3-trans analogue was 10-fold more active than an analogue having a 1′-ketoalkyl moiety at C-2 (A-factor type analogue). Methoxylation or deletion of either one of the two hydroxy groups in virginiae butanolide C analogues caused a 100 to 1, 000-fold decrease in activity, thus indicating the importance of the two hydroxy groups in virginiamycin induction. © 1988, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.