Corrin ring system

Incorporation of cobalt into the corrin ring system modifies the reduction potentials of... 

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. 

In consideration of a possible biosynthetic route for the corrin ring system, Eschenmoser devised a reductive, acid-catalyzed cyclization of a dehydrosecocorrinoid complex (108) to the corrin (109), possibly via a diradical intermediate (equation 53).267... 

Several macrocyclic ligands are shown in Figure 2. The porphyrin and corrin ring systems are well known, the latter for the cobalt-containing vitamin Bi2 coenzymes. Of more recent interest are the hydroporphyrins. Siroheme (an isobacteriochlorin) is the prosthetic group of the sulfite and nitrite reductases which catalyze the six-electron reductions of sulfite and nitrite to H2S and NH3 respectively. The demetallated form of siroheme, sirohydrochlorin, is an intermediate in the biosynthesis of vitamin Bi2, and so links the porphyrin and corrin macrocycles. Factor 430 is a tetrahydroporphyrin, and as its nickel complex is the prosthetic group of methyl coenzyme M reductase. F430 shows structural similarities to both siroheme and corrin. 

Figure 28-2. The structure of vitamin B12 (cobalamin). Vitamin B12 is composed of a planar corrin ring containing a cobalt atom at the center. The corrin ring system is composed of four pyrrole rings and is similar to porphyrin in heme. The cobalt atom is coordinated to the nitrogens of each pyrrole ring and to a dimethylbenzimidazole group. The R group attached to the sixth coordination site of the cobalt atom in vitamin B12 can be a -CN, -OH, -CH3, or adenosyl group.

The use of metal ions as templates for macrocycle synthesis has an obvious relevance to the understanding of how biological molecules are formed in vivo. The early synthesis of phthalocyanins from phthalonitrile in the presence of metal salts (89) has been followed by the use of Cu(II) salts as templates in the synthesis of copper complexes of etioporphyrin-I (32), tetraethoxycarbonylporphyrin (26), etioporphyrin-II (78), and coproporphyrin-II (81). Metal ions have also been used as templates in the synthesis of corrins, e.g., nickel and cobalt ions in the synthesis of tetradehydrocorrin complexes (64) and nickel ions to hold the two halves of a corrin ring system while cycliza-tion was effected (51), and other biological molecules (67, 76, 77). 

Figure 5 Outline of the total synthesis of cobyric acid (Figure 1) on the way to vitamin B12 top the ETH approach via an A/D ring closure of the corrin ring system bottom the Harvard/ETH approach via an A/B ring closure...

FIGURE 16.13. Formula for vitamin B12. (a) Simplified formula where Me = CH3, Ac = CH2CONH2, Pr = CH2CH2CONH2. (b) Details of the numbering in the corrin ring system. 

Dorothy Hodgkin, who obtained a Nobel Prize in 1965 for her X-ray diffraction work, wrote, a great advantage of X-ray analysis as a method of chemical structure analysis is its power to show some totally unexpected and surprising structure with, at the same time, complete certainty. Her X-ray diffraction studies are the reason that we now know that penicillin has a /3-lactam structure and that vitamin B, contains what is now known as a corrin ring system. The results of all X-ray diffraction studies are used by chemists and biochemists, and these scientists need to be able to appreciate the significance and extent to which such results are useful and precise. 

The structure of the cobalamin family of compounds is shown in Figure 38-16. The corrin ring system of four pyrrole rings linked by three methene bridges is sim-... 

Vitamin Bj2 also has a ring system similar to porphyrin, but one of the methine bridges is missing. The ring system of vitamin Bj2 is known as a corrin ring system. The metal atom in vitamin B12 is cobalt (Co ). The chemistry of vitamin B12 is discussed in Section 25.7. 

FIGURE G.2 (a) The Structure of vitamin B12. In the commercial form of the vitamin (cyanocobalamin), R = CN. (b) The corrin ring system, (c) In the biologically active form of the vitamin (5 -deoxyadenosylcobalamin), the 5 carbon atom of 5 -deoxyadenosine is coordinated to the cobalt atom. For the structure of adenine, see Section 25.2. 

The corrin ring system is formed from uroporphyrinogen III (D 10.1) by reductive contraction of the porphyrin ring. All seven extra methyl groups of the corrin ring (encircled in the formula given above) are derived from L-methionine. 

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