Total synthesis of 0231B, an inhibitor of 3alpha-hydroxysteroid dehydrogenase produced by Streptomyces sp. HKI0231.
The new inhibitors of 3alpha-hydroxysteroid dehydrogenase, 0231A 1 and 0231B 2, have a unique benz[c,d]indol-3(1H)-one structure in their molecules. In our advanced studies on indole chemistry, we have developed an efficient synthetic method for benz[c,d]indol-3(1H)-one derivatives. We report here its application to the synthesis of 0231B in 10 steps (8.1% overall yield) from 6-methylindole 8 by introducing an acyl group into the 3-position of the indole nucleus, cyclization of the side chain at the 3-position to the 4-position and subsequent elimination of the phenyl group, and conjugate addition of the substituted phenyl group.
The United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Taichi
T
Komoda
Yoshihiko
Y
Shinoda
Shin-ichi
S
Nakatsuka
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000215:Acylation; D001555:Benzene Derivatives / Q000737:chemistry; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry; D013302:Streptomyces / Q000201:enzymology*
C434149:0231B, Streptomyces; D001555:Benzene Derivatives; D004791:Enzyme Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles; D015096:3-Hydroxysteroid Dehydrogenases