Microbial conversion of mevinolin.
About 3000 microorganisms (bacteria, Actinomyces, Zygomyces, Deuteromyces) were screened for their capacity to convert mevinolin. Absidia coerulea IDR 705 was found to produce two hydroxylated derivatives of mevinolin, 2 and 3. Compound 2 is a new transformation product while compound 3 was described as a chemical modification product of mevinolin. By combination of spectroscopic techniques, the structures of 2 and 3 were identified with beta,delta-dihydroxy-7-(1,2-dihydro-2-hydroxymethyl-6-methyl-naphthal en-1-yl)-heptanoic acid delta-lactone and beta,delta-dihydroxy-7-[1,2,3,5,6,7,8,8a-octahydro-3,5-dihydroxy-2, 6-dimethyl-8-(2-methyl-butyryloxy)-naphthalen-1-yl]-hepta noi c acid delta-lactone, respectively. The inhibitory effects of the two derivatives on the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase were similar to that of mevinolin.
Jekkel
A
A
Institute for Drug Research Ltd., Budapest, Hungary.
Kónya
A
A
Ilkóy
E
E
Boros
S
S
Horváth
G
G
Sütó
J
J
D000818:Animals; D001711:Biotransformation; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C109012:dihydroxy-7-(1,2,3,5,6,7,8,8a-octahydro-3,5-dihydroxy-2,6-dimethyl-8-(2-methylbutyryloxy)naphthalen-1-yl)heptanoic acid lactone; C109011:dihydroxy-7-(1,2-dihydro-2-hydroxymethyl-6-methylnaphthalen-1-yl)heptanoic acid; D008148:Lovastatin