Corrin ligands

In addition to these low field resonances the chemical shift of the coordinated methyl group falls at —0.19 and the methyl portion of the coordinated ethyl group has a chemical shift of —0.61. By comparing these numbers with the chemical shifts of the ethyl protons in the analogous ethyl porphyrin derivative (129), in which the resonance positions are all above —5, it has been concluded that there is little or no ring current in the corrin ligand system. 

Eschenmoser [15] has recently alluded to the concepts of structure-directed synthesis and autochthonous reactivity — the propensity of certain systems to undergo reactions as a consequence of their intrinsic molecular structural factors — within the context of certain biomolecules, particularly the organic cofactor, vitamin B12. The formation of the AD ring junction in the corrin ligand had to be regarded as a major hurdle in any proposed chemical synthesis of cobyric acid (5) (Fig. 2), and hence of vitamin B12. However, driven initially by the desire to identify a dark, and therefore potentially biomimetic, variant of the photochemical... 

Vitamin B12 (1) was discovered some 55 years ago as the (extrinsic) antipemicious anemia factor, important for human and animal metabolism The cobalt complex (1) was structurally characterized by X-ray analysis in the laboratory of D.C. Hodgkin. In these studies, the unique buildup of the tetrapyrrolic corrin ligand and the intramolecularly coordinating pseudo-nucleotide function of the vitamin were discovered. ... 

The complex and novel structure of the corrin ligand prompted a series of early investigations of its chemistry,... 

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 corrin ligand and the basic motif of the nucleotide chain are widely conserved structural units in the natural corrins. Norpseudovitamin B12 (8) is the first example of a natural corrinoid with a modified isopropanolamine linker it is (the isolation form of) the cofactor of perchloroethene-dehalogenase in an obligate anaerobe. The nucleotide bases (a 5,6-dimethylbenzimidazole in the cobalamins) of natural complete corrins from different bacterial sources also exhibit variability in their constitution (Figure 2). ... 

So far, for the highly oxygen-sensitive Co -forms of cobalt-corrinoids (such as Co -cobalamin, (6)), information from X-ray analysis on their three-dimensional structure is not available. However, in these strongly nucleophihc, highly reduced cobalt complexes, the diamagnetic Co -center (a d metal ion, isoelectronic with a Ni"-ion) presumably is ligated by the corrin ligand only, in a tetracoordinated, nearly square-planar fashion. As a consequence, the Co -forms of complete corrins would have to be base-off, that is, the nucleotide function would not be attached to the central cobalt ion. 

The natural corrinoids are made exclusively by microorganisms, which are also exploited on a large scale for the industrial production of vitamin B12. The biosynthesis of the corrin ligand branches off from that of the other porphinoids at their common tetrapyrrolic intermediate, uroporphyrinogen III, and has been studied both in aerobic and in anaerobic... 

Figure 1 In the above structure, R = CN denotes cyanocobalamin (CN-Cbl), whilst R = OH is hydroxocobalamin (OH-Cbl) R = 5 -deoxyadenosyl is coenzyme B12 (adenosylcobalamin, AdoCbl) and R = Me is methylcobalamin (MeCbl). By definition all cobalamins contain 5,6-dimethylbenzimidazole, which is the so-called 6th ligand to cobalt in the above structure. Substances containing the corrin ligand, i.e. the planar 14 electron p-system embracing cobalt in the above structure, are also called corrinoids.

The aquo complex has a pKa of 7.8, which compares with that of 5.7 for the aquopentaamminecobalt(III) complex at 298 K. The difference has been mainly ascribed to the difference in solvation of the two complexes, although the corrin ligand bears a negative charge, which reduces the positive charge and therefore the Lewis acidity of the metal ion. The standard reduction potential between pH 2.9 and 7.8 is —0.04 V vs. SCE, featuring the conversion from aquocobalamin with bound benzimidazole (base on) to base-on cob(II)alamin. The potential decreases with pH above pH 7.8 down to —0.3 V. The reduced form is five-coordinate, without the water molecule above pH 2.9, and low-spin.The system can be further reduced at a potential of —0.85 V to... 

Fig. 25-F-6. (a) The corrin ligand system, (b) Structure of cobyric acid, the simplest...

Pfaltz has shown that his original semi-corrin ligand complexes (9.02) are best suited to the cyclisation of the diazoketone (9.22). The corresponding reaction with a bis-oxazoline afforded only 77% ee. ... 

An interesting [1.5] sigmatropic rearrangement of the 11 methyl group into the 12 position of ring C and tautomerizations (a, b) at the 10,15 methylene linkages complete the formation of the corrin ligand (148) of vitamin B12. 

B12-derivatives [29], which builds on the convention that atom numbers of the heavy atoms of a substituent reflect the number of the points of attachment to the corrin ligand and are indexed consecutively [30]. 

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