Benz[c,ii]indol-3(l //)-one 10 and 11, a major part of indole alkaloids 0231A 2 and 023IB 3 produced by Streptomvces sp. HKI0231, new enzyme inhibitors of 3 a-hydroxysteroid dehydrogenase, were efficiently synthesized by cyclization of 3-(4'-methylcinnamoyl)indole derivatives 6c and 7c and elimination of toluene.In the biosynthesis of ergot alkaloids 1, a phenyl group is first introduced at 4-position of tryptophan." Although many attempts introducing such substituent at the position of indole nucleolus have been studied for a long time, no successful method was reported 2 ' except a few cases. 3 " 5 ' 1 Ergot alkaloids 2:R = OMe 0231A 3 : R = Η 023IB
Figure 1.In our synthetic studies on indole alkaloids, we have found intra-and intermolecular cyclization toward the 4-position of indole nucleus in cases of dehydrotryptophan and vV-acylindole derivatives. 5 ' Recently, we found a novel synthetic method of benz[t\cf|indol-3(l/7)-one derivatives 5, whose common structure was found in enzyme inhibitor 0231A 2 and 023IB 3 from Streptomyces sp. HKI0231. 6) via intramolecular cyclization of substituted 3-cinnamoyIindoles 4 and subsequent elimination of benzene (Fig. 2>. 7 ' Brought to you by |
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.
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