Preparation of alkyl-substituted indoles in the benzene portion. Part 9. Synthesis of (1aS,8bS)-1-tert-butyloxycarbonyl-8-formyl-1,1a,2,8b-tetrahydroazirino [2',3':3,4]pyrrolo[1,2-a]indole. Model study for the enantiospecific synthesis of ziridinomitosenes

Article abstract of DOI:10.1248/cpb.41.854

Effective pathways for an enantiospecific synthesis of (1aS,8bS)-1-tert-butyloxycarbonyl-8-formyl-1,1a,2,8b-tetrahydroazirino [2',3':3,4]pyrrolo[1,2-a]indole (8) were investigated as a preliminary experiment aiming at chiral syntheses of aziridinomitosenes 5 and (1aS,8bS)-8-[[(aminocarbonyl)oxy]methyl]-5-formyl-7-hydroxy-1,1a,2,8b- tetrahydroazirino[2',3':3,4]pyrrolo[1,2-a]indole (6a). An aldehyde 14, derived from L-serine was condensed with 2-lithio-1-(phenylsulfonyl)indole (10) to afford diastereomers 15a and 15b, whose stereochemistry was unambiguously determined by ¹H-NMR studies of the 1,3-dioxane derivatives 17a, 17b, and 18 as well as the X-ray crystallographic analysis of a dihydropyrrolo[1,2-a]indole derivative 31a. The latter compound was prepared from 15a via the following operations (Chart 5): (i) removal of the acetonide and the indole-protecting groups, followed by acetylation to form 29a, (ii) Vilsmeier reaction to produce 30a, and (iii) hydrolysis of acetyl groups, partial methanesulfonylation (mesylation), and treatment with potassium carbonate in acetonitrile. A diastereomer 31b was obtained from 15b in a similar manner. Both isomers 31a and 31b afforded the desired compound 8 upon treatment with a mesylation reagent followed by potassium tert-butoxide in tetrahydrofuran.

Full text of DOI:10.1248/cpb.41.854

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