Cobalt compounds methylcobalamin

The total syntheses have yielded cobyric acid and thence cyanocobalamin. Routes to other cobalamins, eg, methylcobalamin and adenosylcobalamin, are known (76—79). One approach to such compounds involves the oxidative addition of the appropriate alkyl haUde (eg, CH I to give methylcobalamin) or tosylate (eg, 5 -A-tosyladenosine to yield adenosylcobalamine) to cobalt(I)alamine. 

Figure 15.3 Structural formula of deoxyadenosylcobalamin (coenzyme B, ). (a) A plan view of the corrin nucleus with substituents, (b) The position of the remaining two ligands of the cobalt atom. No attempt is made to show correct stereochemical relationships. Related compounds have different groups in place of the 5 -deoxyadenosyl group cyanocobalamin, (vitamin Bi2)-CN hydroxycobalamin, (vitamin Bi2)-0H methylcobalamin, (vitamin Bi2)-CH3.

Although three early papers briefly discussed reactions between methylcobalamin and mercury compounds (30-32), the most systematic investigation has come from Wood and co-workers (33). They proposed the mechanism shown in Fig. 1, with values for the various rate constants presented in Table I. Species 2 and 3, in which the benzimidazole nitrogen no longer bonds to the cobalt atom, are termed base-off compounds, whereas 1 is base-on methylcobalamin and 4 is aquocob(III)alamin, the usual product of aqueous transmethylation by 1. Each one of these species has a unique ultraviolet-visible spectrum, which allows quantitative studies by spectrophotometric techniques to be made (28, 32, 33). The mercuric acetate-1 exchange is so rapid that it must be studied using stopped-flow kinetic techniques (33). 

Vitamin B12 is a biologically active corrinoid, a group of cobalt-containing compounds with macrocyclic pyrrol rings. Vitamin B12 functions as a cofactor for two enzymes, methionine synthase and L-methylmalonyl coenzyme A (CoA) mutase. Methionine synthase requires methylcobalamin for the methyl transfer from methyltetrahydrofolate to homocysteine to form methionine tetrahy-drofolate. L-methylmalonyl-CoA mutase requires adenosylcobalamin to convert L-methylmalonyl-CoA to succinyl-CoA in an isomerization reaction. An inadequate supply of vitamin B12 results in neuropathy, megaloblastic anemia, and gastrointestinal symptoms (Baik and Russell, 1999). 

Methylcobalamin (I, R = —CH3) and the vitamin Bi2 coenzyme (I, R = 5 -deoxyadenosyl) are the only known naturally occurring organometailic compounds. Both are derivatives of vitamin 8t2 (cyanocobalamin, I, R = —CN)and both can be synthesized from Bn but are best prepared from hydroxocobalamin. These and numerous other derivatives of Bn containing a cobalt-carbon bond are known, and provided the cobalt is bonded to a primary carbon atom the complexes are thermally very stable, but always photochemically labile as a result of homolytic cleavage of the cobalt-carbon bond. 

The various photochemical studies of these compounds have been conducted primarily because of the interest of researchers in the synthesis, properties, and biological activity of vitamin and its derivatives. The structure of vitamin Bj2, as determined by Crowfoot-Hodgkin et al. 109), is shown in Fig. 2. It consists of cobalt in a corrin ring complexed axially by an a-S, 6-dimethylbenzimidazole nucleotide and by cyanide ion. Replacement of the axial CN by a methyl group gives methylcobalamin, and by 5 -deoxyadenosine gives coenzyme Bj2. The formal oxidation state of... 

Methylcobalamin can methylate many compounds, including metals. The reactions of alkylcobalamins depend on cleavage of the alkyl — cobalt bond, which can result in Co(l) and an alkyl cation, Co(II) and an alkyl radical, or Co(III) and an alkyl anion, with the radical mechanism being the most common. The alkyl products can then react in a number of ways. Some of the reactions include the following ... 

Structure of the cobalamin family of compounds. A through D are the four rings in the corrinoid ring system. The B ring is important for cobalamin binding to intrinsic factor. If R = -CN, the molecule is cyanocobalamin (vitamin B12) if R = 5 -deoxyadenosine, the molecule is adenosylcobalamin if R = -CH3, the molecule is methylcobalamin. Arrows pointing toward the cobalt ion represent coordinate-covalent bonds. 

Description. Vitamin B12 is the largest and most complex of all the vitamins. It is unique among vitamins in that it contains a metal ion, cobalt. For this reason cobalamin is the term used to refer to compounds having B12 activity. Methylcobalamin and 5-deoxyadenosyl cobalamin are the forms of vitamin B12 used in the human body. The form of cobalamin used in most supplements, cyano-cobalamin, is readily converted to 5-deoxyadenosyl and methylcobalamin. 

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