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

J Antibiot (Tokyo). 1988 Dec;41(12):1828-37. doi: 10.7164/antibiotics.41.1828.

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.

MeSH terms

  • 4-Butyrolactone / analogs & derivatives
  • 4-Butyrolactone / pharmacology*
  • Anti-Bacterial Agents / biosynthesis*
  • Furans / pharmacology*
  • Streptomyces / metabolism*
  • Structure-Activity Relationship
  • Virginiamycin / biosynthesis*

Substances

  • Anti-Bacterial Agents
  • Furans
  • virginiamycin butanolide C
  • Virginiamycin
  • 4-Butyrolactone