Reductive dealkylation of alkylcobaloximes, alkylcobalamins, and related compounds: Simulation of corrin dependent reductase and methyl group transfer reactions

Abstract

The cobalt-carbon bond in alkylcobaloximes, alkylcobalamins, and alkylcobalt derivatives of related chelates is reductively cleaved by thiols and dithiols. The cleavage occurs optimally in neutral or mildly acidic anaerobic medium and involves trans-attack on the cobalt atom by the thiol as the first step. The initial products of the cleavage reaction are carbanionic species which react with protons of the solvent to form alkanes. Consistent with this mechanism, the dealkylation is inhibited by bases competing with thiols for the cobalt coordination site. The methyl carbanionic species generated by the reductive cleavage of methylcobinamide and methylcobaloximes may be trapped by carbon dioxide to form acetate. The latter reaction represents a plausible model for the terminal step of acetate biosynthesis from methylcobalamin and carbon dioxide by cell-free extracts of Clostridium thermoacelicum. Reductive Co C bond cleavage reactions also provide pertinent information concerning the rate-determining step in corrin or coenzyme B 12-dependent reductase reactions, such as methane biosynthesis by Methanobacillus omelianskii, ribonucleotide reduction by ribonucleotide reductase of Lactobacillus leichmanniii, methylarsine and methylselenide formation by cell extracts of Methanobacterium strain M.O.H. in the presence of arsenite or selenite.