7-Decarboxymethyl-cobyrinates: vitamin B12-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.
Institute of Organic Chemistry and Centre of Molecular Biosciences, University of Innsbruck, Centre of Chemistry and Biomedicine, Innrain 80/82, 6020 Innsbruck, Austria. bernhard.kraeutler@uibk.ac.at
Bernhard
B
Kräutler
D002244:Carbon / Q000737:chemistry*; D045728:Corrinoids / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*
D045728:Corrinoids; C473700:corrin; C010895:cobyrinic acid; D002244:Carbon; D014805:Vitamin B 12