Synthesis of 5,6-substituted benzimidazoles and their evaluation as potential intermediates in the anaerobic vitamin B12 biosynthesis pathway

Abstract

Although benzimidazoles are well-recognized compounds in medicinal chemistry, they occur in the natural world primarily as lower ligands of Vitamin B-12 and other cobamides. In this study, we present the synthesis of 5-methoxy-6-methylbenzimidazole and 5-hydroxy-6-methylbenzimidazole, and demonstrate their ability to produce functional cobamides and N-1 '-alpha-glycosidic-benzimidazolyl-ribosylphosphate isomers which are putative B-12 biosynthesis intermediates.