Structure-activity relationships of virginiae butanolide C, an inducer of virginiamycin production in Streptomyces virginiae.
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.
Nihira
T
T
Department of Fermentation Technology, Faculty of Engineering, Osaka University, Japan.
Shimizu
Y
Y
Kim
H S
HS
Yamada
Y
Y
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D005663:Furans / Q000494:pharmacology*; D013302:Streptomyces / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014769:Virginiamycin / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D005663:Furans; C052546:virginiamycin butanolide C; D014769:Virginiamycin; D015107:4-Butyrolactone