SYNTHESIS OF 4-AZA-5,6-DIMETHYLBENZIMIDAZOLE AND BIOSYNTHETIC PREPARATION OF 4-AZA-5,6-DIMETHYLBENZIMIDAZOLYLCOBAMIDE AND 7-AZA-5,6-DIMETHYLBENZIMIDAZOLYLCOBAMIDE

We report on the preparation of 4-aza-5,6-dimethylbenzimidazolylcobami de and 5,6-dimethyl-7-azabenzimidazolylcobamide. These vitamin B12-ana logs were required as reference compounds for comparison with a corrin oid previously isolated in small amounts from Eubacterium limosum grow n in the presence of 4(5)-aminoimidazole. 4(7)-Aza-5,6-dimethylbenzimi dazole was synthesized from N-1-benzyl-4-nitroimidazole which was redu ced to N-1-benzyl-4-aminoimidazole and condensed with 1-dimethylamino- 2-methylbutan-3-one to yield N-1-benzyl-4-aza-5,6-dimethylbenzimidazol e. The benzyl group of this compound was split off by catalytic hydrog enation to form 4(7)-aza-5,6-dimethylbenzimidazole. 4(7)-Aza-5,6-dimet hylbenzimidazole was transformed by a growing culture of Propionibacte rium shermanii into 4-aza-5,6-dimethylbenzimidazolylcobamide and 5,6-d imethyl-7-azabenzimidazolylcobamide. Both vitamin B12-analogs were alm ost as active as Vitamin B12 in a growth test with the vitamin B12-dep endent Escherichia coli-mutant DSM 4261.