Yoshio Kigawa

Studies on the syntheses of heterocylic compounds—762: Synthesis of 3-benzyl-6-methyl-2-oxo-3,6-diazabicyclo[3.1.0]hexane as a synthetic intermediate of mitomycins

Abstract (±)-1-Benzyl-3α-hydroxy-4β-methylamino-2-oxopyrrolidine ( 15 ) and its cis -isomer ( 16 ) were synthesised from 1-benzyl-4-ethoxycarbonyl-2,3-dioxopyrrolidine ( 2 ) in several steps. The former ( 15 ) was converted to 3-benzyl-6-methyl-2-oxo-3,6-diazabicyclo[3.1.0]hexane ( 17 ) with a mixture of triphenylphosphine, carbon tetrachloride and triethylamine.

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

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).

Studies on the syntheses of heterocyclic compounds. Part 676. Synthesis of 1-substituted 7-methoxymitosenes

On treatment with lead tetra-acetate in acetic acid, the 2,3-dihydro-1H-pyrrolo[1,2-a]indoles (4)–(8) were selectively acetoxylated at C-1 to give the acetates (13)–(17). The acetates (16) and (17) and 1-acetoxy-2,3-dihydro-7-methoxy-6-methyl-5,8-dioxo-1H-pyrrolo[1,2-a]indole-9-carbaldehyde (27) were hydrolysed to the corresponding alcohols (20), (21), and (28). The alcohols (20) and (21) were oxidised to the 1-ketones (22) and (23), and (28) was chlorinated with methanesulphonyl chloride and lithium chloride in dimethylformamide to give 1-chloro-2,3-dihydro-7-methoxy-6-methyl-5,8-dioxo-1H-pyrrolo[1,2-a]indole-9-carbaldehyde(29). On heating the acetates (13), (14), and (17) in acetic acid, elimination of acetic acid occurred to yield the 3H-pyrrolo[1,2-a]indoles (24)–(26).