Corrin Corrinoids

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... 

Isomers are, of course, possible when the equatorial ligand lacks a plane of symmetry, as in the corrinoids [see (HI)]. All the acetamide side chains project to one side of the corrin ring, which we shall call the upper side, and all the propionamide side chains and the nucleotide side chain to the lower side. Isomers are then theoretically possible whenever the two axial ligands are different, and their existence has been shown experimentally for corrinoids where one axial ligand is CN , Me, or Et and the other is H2O or is absent [for further details see Section 8.2 of ref. (136)]. Salen and BAE also show minor deviations from planarity due to the bending of the two halves (mentioned above in Section II,B,2) and to torsion about the C—C bonds in the ethylene bridge (see references in Table I), but these are not expected to give rise to separable isomers. 

One of the major reasons for studying the ESR of this series of Co(II)-corrinoids is that this spectral tool may give information on the mechanism of corrin-dependent enzymes. Cleavage of the Co—C—cr-bond has been studied in a few enzymes by using Co(II) ESR, and there is evidence... 

The most exciting research is yet to be performed on 13C NMR of the corrin enzymes. This could be accomplished by biosynthesis of C-13 enriched samples of biologically active B12 derivatives followed by their incorporation into enzymes. Since it has been shown that 13C-spectra of corrinoids are well resolved, and sensitive to small changes in the molecular conformation, then one could hope to get quite detailed information pertinent to the binding of B12 and to the mechnism of enzyme catalysis. 

Copper-sulfide cluster 884s Coproporphyrin III 843,845s Comified cell envelope 439 Corrin in transmethylation 592 Corrin ring 867, 868 Corrinoid-dependent synthesis of acetyl-CoA 876, 877 Cosmarium 22 COSY-NOESY diagram 143 Cotransport (symport) process 411,416,417 Coulomb 283... 

Cu11 corrinoids do not coordinate axial ligands.264 MCD, ESR and ENDOR spectra indicate the Cu atom is in the N4 plane with an unpaired electron in a dxl yl orbital which has little interaction with the corrin n system. 

The structures of the biologically active forms of B12 were solved relatively recently (1961) (78) and were shown to contain a cobalt atom surrounded by a corrin ring as shown in Fig. 16 (80). The crystal structure also showed a cobalt-carbon a bond which was quite surprising since the few compounds with cobalt-carbon a- bonds known at that time were quite unstable (79). The corrin ring is similar to the porphyrin ring, but its greater saturation imports less rigidity than the porphyrin. Corrinoids with the axial 5,6-dimethylbenzimidazole substituent are called cobalamins. Vitamin B12 with Co(III) and CN in the top axial position is... 

The parent compound used for the nomenclature of corrinoids is the naturally occurring system corrin, whose structure is shown in Fig. 6. 

Corrin and octadehydrocorrin represent the extremes in the family of corrinoid compounds between these two structures there are those macrocycles in which additional double bonds can be systematically introduced in the ring. 

The corrinoid macrocycle has undergone a complicated series of reactions in order to give the final product the corrin ring has expanded, one angular methyl... 

Of the corrinoid-agarose gels mentioned above, the corrinoids immobilized through sidechains of the corrin ring were the most effective affinity adsorbents. Although the enzyme was adsorbed com-... 

Although the cobalt corrinoids have been studied extensively in. the last two decades (J), the significance of corrin as an equatorial ligand is not well understood. To characterize coenzyme B12 as an organocobalt derivative, a search for model cobalt complexes that can form a Co-C bond axial to a planar equatorial ligand has been stimulated. Studies on model systems (2-13), particularly on the cobaloxime derivatives (2-7), characterized their respective chemistry, but it is still not easy to establish a general correlation between the structure of an equatorial ligand and the properties of cobalt complex... 

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. ... 

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