Vitamin cobalt corrins

In comparison to the porphyrins, the corrin nucleus contains one less atom in its innermost ring (that is, it contains a 15-membered ring) and, on coordination, only one NH proton is lost to give the macrocycle a single negative charge. A cobalt corrin complex occurs as part of the structure of vitamin B12. 

The unmatched complex structure of the low-molecular weight natural product vitamin Bn posed a challenge to synthetic chemistry, which was met in the early 1970s by Eschemnoser and by Woodward and their coworkers. The biosynthesis of the structure of natural cobalt-corrins is no less intricate and facets of its pathways still remain to be uncovered (see section 2.3). 

Subsequent to the original quest for vitamin B12 (1), driven by medicinal purposes mainly, further investigations on the natural corrinoids laid bare the central roles of the Bi2-coenzymes in the metabolism of microorganisms, in particular. These primitive organisms uniquely possess the capacity to build up the complex B12 structure in nature, in which they may vary the constitution of the nucleohde ftmchon in a species-specihc way (Figure 2). The cobalt-corrins, in turn, have been proposed to be structural and functional renmants of early (primihve) forms of life, where presumably, central metabolic processes could rely considerably on organometalhc chemistry at cobalt and nickel centers. ... 

Unravelling the biosynthetic steps leading from uro gen 111 to cobalamin, the finished cobalt corrin at the heart of vitamin B,2, is a story that has been likened to the climbing of Mt. Everest. It will one day be seen as the solution to one of chemistry s and biochemistry s greatest puzzles. Only the outline of the "ascent" will be given here. 

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). 

The structure of the diamagnetic, cherry-red vitamin B12 is shown in Fig. 26.6 and it can be seen that the coordination sphere of the cobalt has many similarities with that of iron in haem (see Fig. 25.7). In both cases the metal is coordinated to 4 nitrogen atoms of an unsaturated macrocycle (in this case part of a corrin ring which is less symmetrical and not so unsaturated as the porphyrin in haem) with an imidazole nitrogen in the fifth position. A major... 

Figure 26.6 Vitamin B12 (a) a corrin ring showing a square-planar set of N atoms and a replaceable H, and (b) simplified stmcture of B12. In view of the H displaced from the corrin ring, the Co-C bond, and the charge on the ribose phosphate, the cobalt is formally in the - -3 oxidation state. This and related molecules are conveniently represented as r...

Scheme 1 outlines the retrosynthetic analysis of the Woodward-Eschenmoser A-B variant of the vitamin B12 (1) synthesis. The analysis begins with cobyric acid (4) because it was demonstrated in 1960 that this compound can be smoothly converted to vitamin B12.5 In two exploratory corrin model syntheses to both approaches to the synthesis of cobyric acid,6 the ability of secocorrinoid structures (e. g. 5) to bind metal atoms was found to be central to the success of the macrocyclization reaction to give intact corrinoid structures. In the Woodward-Eschenmoser synthesis of cobyric acid, the cobalt atom situated in the center of intermediate 5 organizes the structure of the secocorrin, and promotes the cyclization... 

Vitamin B12 (Fig. 1) is defined as a group of cobalt-containing conoids known as cobalamins. The common features of the vitamers are a corrin ting (four reduced pyrrole rings) with cobalt as the central atom, a nucleotide-like compound and a variable ligand. Vitamin B12 is exceptional in as far as it is the only vitamin containing a metal-ion. The vitamers present in biological systems are hydroxo-, aquo-, methyl-, and 5 -deoxyadenosylcobalamin. 

New developments in the field of vitamin B12 reactions of the cobalt atom in corrins and vitamin B12 model compounds. G. N. Schrauzer, Angew. Chem., Int. Ed. Engl., 1976,15, 417-426 (67). 

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... 

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.

Vitamin B12 (cobalamine) is one of the most complex low-molecular-weight substances occurring in nature. The core of the molecule consists of a tetrapyrrol system (corrin), with cobalt as the central atom (see p. 108). The vitamin is exclusively synthesized by microorganisms. It is abundant in liver, meat, eggs, and milk, but not in plant products. As the intestinal flora synthesize vitamin B12, strict vegetarians usually also have an adequate supply of the vitamin. 

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. 

Coenzyme B12 is the cofactor form of vitamin B 2, which is unique among all the vitamins in that it contains not only a complex organic molecule but an essential trace element, cobalt. The complex corrin ring system of vitamin B12 (colored blue in Fig. 2), to which cobalt (as Co3+) is coordinated, is chemically related to the porphyrin ring system of heme and heme proteins (see Fig. 5-1). A fifth coordination position of cobalt is filled by dimethylbenzimidazole ribonucleotide (shaded yellow), bound covalently by its 3 -phosphate group to a side chain of the corrin ring, through aminoisopropanol. 

A catalytic variation of the cobalt method is the vitamin BI2a-mediated reaction to provide C-glycosides [24], The intermediate in this chain mechanism is the sugar cobalamine 45 formed by reaction of the precursor 43 with vitamin B 2a 44 (the brackets in Scheme 10 represent the corrin system) [25]. 

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