7‐Decarboxymethyl‐cobyrinates: Vitamin B 12 ‐Derivatives that Lack the c‐Side Chain

The synthesis of cobyrinic acid derivatives by reduction of dehydrocobyrinates is largely unexplored. It is, however, a rational path to B 12 analogues that lack specific substituents of the corrin moiety of natural B 12 derivatives. The partial syntheses of four epimeric 7‐decarboxymethyl‐cobyrinates is described, which is achieved by reduction of Δ7‐dehydro‐7‐de[carboxymethyl]‐cobyrinate with zinc or with the ‘prebiotic’ reducing agent formic acid. A direct and remarkably efficient route was found to 7‐decarboxymethyl‐cobyrinates, which are cobyrinic acid derivatives in which the c‐side chain at ring B of vitamin B 12 is missing. The structures of the hexamethyl‐7‐decarboxymethyl‐cobyrinates were characterized and the stereochemical and conformational properties at their newly saturated ring B were analyzed. The stereochemical outcome of the reduction was found to depend strongly on the reaction conditions. In 7‐decarboxymethyl‐cobyrinates, both peripheral carbon centres of ring B carry a hydrogen atom, and the characteristic quaternary carbon centre at C7 of the cobyrinic acid moiety of vitamin B 12 is lacking. The still highly substituted 7‐decarboxymethyl‐cobyrinates are readily dehydrogenated in the presence of dioxygen, furnishing 7‐de[carboxymethyl]‐Δ 7 ‐dehydro‐cobyrinate as the common, unsaturated oxidation product. The noted stability of vitamin B 12 and of other Co III ‐cobyrinates in the presence of air is a consequence of their highly substituted corrin macrocycle, a finding of interest in the context of chemical rationalizations of the B 12 structure.