Studies on the synthesis of heterocyclic compounds. Part 832. A simple and efficient synthesis of apomitomycin derivatives; a potential intermediate for mitomycin synthesis

Abstract

Condensation of pyrrolidine-2-thione (21) with methyl α-bromo-(2-bromo-4,5-dimethoxyphenyl)acetate (15) gave methyl (Z)-α-(2-bromo-4,5-dimethoxyphenyl)-α-pyrrolidin-2-ylideneacetate (25) in high yield. Several other methyl (Z)-α-aryl-α-[3-acetoxy-4-(N-ethoxycarbonyl-N-methylamino)pyrrolidin-2-ylidene]acetates (26)–(31) were also synthesised in good yields from reaction of the corresponding phenylacetates (15), (12), and (13) with trans-3-acetoxy-4-(N-ethoxycarbonyl-N-methylamino)pyrrolidine-2-thione (20). Treatment of compounds (25)–(31) with sodium hydride and copper(I) bromide in dimethylformamide afforded methyl 2,3-dihydro-6,7-dimethoxy-1H-pyrrolo[1,2-a]indole-9-carboxylate (34) and the methyl (±)-trans-1-acetoxy-2-(N-ethoxycarbonyl-N-methylamino)-2,3-dihydro-1H-pyrrolo[1,2-a]indole-9-carboxylates (35)–(37) in good yields. Methyl (±)-trans-1-acetoxy-2-(N-ethoxycarbonyl-N-methylamino)-2,3-dihydro-7-methoxy-6-methyl-1H-pyrrolo[1,2-a]indole-9-carboxylate (36) was converted into the 5,8-quinone (3), via the 8-nitro-compound (38).