Total synthesis of 0231B, an inhibitor of 3α-hydroxysteroid dehydrogenase produced by streptomyces sp. HKI0231

Abstract

The new inhibitors of 3α-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. © 2003 by Japan Society for Bioscience, Biotechnology, and Agrochemistry.