Vitamin corrin derivative

Various vitamin B12 derivatives are shown in Figure 6.2, where the R group is usually taken as CN-. This form of vitamin B12 is cyanocobalamin. In the active coenzyme, the CN" is replaced by a 5 -deoxyriboadenosyl residue or by -CH3. Vitamin B12 seems to be the only mammalian substance that contains cobalt. It also has a unique corrin ring structure, which is very similar to that of heme. Metabolic reactions requiring vitamin B12 are discussed in Chapters 19 and 20. 

The skeleton of vitamin 8,2 (i.e., the porphyrin nucleus minus C-20) is called corrin. The compound containing the corrin nucleus is edled a corrinoid. The compound containing the cobalt atom and the standard side chains in the free acid form is called cobyrinic acid, but cobyric acid when the side chains are at positions a, b, c, d, e, g, are in the amide form. Cobyrinic acid substituted with D-l-amino-2-propanol at position f is called cobinic acid. The substituted cobyric acid is called cobinamide. Cobinic acid substituted with d ribofuranose-3-phosphate at position 2 of the aminopropanol is called cobamic acid the substituted cobinamide is called cobamide. Many 8,2 vitamins and derivatives in which the heterocyclic base is 5,6-dimethylbenzimidazole are given the trivial name cobalamin see D. Dolphin, ed., 8,2, Wiley-Interscience, New York, 1982. 

Vitamin B12 is a cobalt metalloporphyrin or corrin derivative it possibly has its origin from uroporphyrinogen III. This vitamin is formed only in certain bacteria, including photosynthetic ones. Both ALA and porphobilinogen (PBG) have been shown to be precursors of Bi2 [13,14]. 

Vitamin B12 (1) was discovered (independently by Folkers and by Smith and Parker) some 60 years ago in the course of a search for the extrinsic antiper-nicious anemia factor (14). However, a physiological role for 1 is unknown and organometallic vitamin B12 derivatives, such as coenzyme B12 (2) and methylcobalamin (3), are the proper B12 cofactors in human, animal, and microbial metabolism (2,3,12,13). The structure of the crystalline red cyano-cobalt(III) complex 1 was solved by X-ray analysis (in the laboratory of D. C. Hodgkin) and was shown to have the unique buildup of a cobalt-corrin (15). 

Although X-ray crystallography provided most of the detailed structural information on cobalt-corrins in the crystal (15-17), NMR spectroscopic studies have contributed to the characterization of vitamin B12 derivatives in solution and have made possible the structural characterization of noncrystallizable vitamin Bi2 derivatives, such as neocoenzyme B12, an epimer of coenzyme B12 (2, AdoCbl) (27). Such studies revealed the organometallic ligands of AdoCbl and of related organometallic B12 derivatives to be bound to the cobalt center in a conformationally flexible way (22,23). 

Porphyrins and chlorophylls are the most widespread natural pigments. They are associated with the energy-converting processes of respiration and photosynthesis in living organisms, and the synthesis of specific porphyrin derivatives is often motivated by the desire to perform similar processes in the test tube. The structurally and biosynthetically related corrins (e.g. vitamin B,j) catalyze alkylations and rearrangements of carbon skeletons via organocobalt intermediates. The biosyntheses of these chromophores are also of topical interest. 

Like many vitamins, cobalamin is functionally active as a derived coenzyme, coenzyme B12. Structurally, this is composed of a corrin ring a haem-like porphyrin ring containing cobalt (Co3+) at the centre held by four coordination bonds. The fifth... 

Vitamin Bjj (8.50, cobalamin) is an extremely complex molecule consisting of a corrin ring system similar to heme. The central metal atom is cobalt, coordinated with a ribofuranosyl-dimethylbenzimidazole. Vitamin Bjj occurs in liver, but is also produced by many bacteria and is therefore obtained commercially by fermentation. The vitamin is a catalyst for the rearrangement of methylmalonyl-CoA to the succinyl derivative in the degradation of some amino acids and the oxidation of fatty acids with an odd number of carbon atoms. It is also necessary for the methylation of homocysteine to methionine. 

Very recently [88] a synthetic derivative of Vitamin B12 where five viologen units have been covalently linked to the 3 side chains of the corrin nucleus has been reported in the literature (Fig. 36). 

In dicyanocobalt(III) a,b,c,d,e,g-hexamethyl-f-stearylamide cobyrinate (derivative 3) the six peripheral amide groups of vitamin B12 have been replaced with methyl ester groups, and the proximal base of the vitamin at the f-position with a stearylamide group (11). Electrodes prepared with this ionophore and DOS as the plasticizer were also selective for thiocyanate and nitrite over the rest of the anions tested. The main anionic interferent was salicylate. In all cases, the response of the electrodes to the preferred anions was sub-Nemstian. Overall, the selectivity pattern obtained with ionophore 3 is similar to that of 2 and to that of the hydrophobic cobyrinate-based electrodes reported previously (5, 12, 13). This observation suggests that in all cobyrinate ionophores the anions interact with the cobalt(III) center, and that the side chains of the corrin ring have a small effect on the selectivity of this interaction. 

Figure 6.2 Forms of vitamin B12 and its derivatives. The central ring structure is called the corrin ring. The R group is usually associated with CN in the vitamin, but other groups are also found. (Reproduced by permission from Diem K, Leutner C. Scientific Tables. Basel Ciba-Geigy, 1971, p. 482.)...

In the context of a chemical study related to problems of vitamin B12 biosynthesis, peripheral C-methylation of the magnesium complex of tctct-OEPc (17) was reported to yield a mixture of isomeric products (18a-c) (83AG(E)631). A similar reaction was found to occur at C-12 of nonamethyl pyrrocorphin (19). One of the by-products of this reaction is the seco-corphinoid derivative 20, which, on complexation with Ni(II) acetate, cyclizes to give an Ni(II) corrinate (21) (84CC583). 

The coenzyme B12 molecule consists of several unique stractural units the corrin ligand, the intramolecularly coordinating nucleotide function, the corrin-bound Co -ion, and the organometallically bound 5 -deoxyadenosyl ligand (Figure 3). The cyanide derivative, vitamin B12 (1), is an isolation artifact that appears not to have a physiological role itself ... 

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... 

Since the initial disclosure of the basic corrin structure, there has been a considerable body of effort devoted toward the synthesis of macrocycles related to this chromophore that may be considered as being intermediates between porphyrin and corrin. These macrocycles, namely the dehydrocorrins (e.g., tetradehydrocor-rin 2.3) and the corroles (e.g., 2.4), represent interesting classes of contracted porphyrins that warrant specific mention here. The interest in these molecules derives in part from the fact that they could represent milestones along the biosynthetic pathway leading to vitamin B12. They are, however, also of interest from a non-biological perspective. Simply stated, this is because corrole-type macrocycles possess unique electronic and chemical characteristics, the study of which can help one to understand better the chemistry of all porphyrin analogs. 

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