Corrin macrocycles

Initial cyclizadons were effected by the addition of an enamine to an imidate ester, both groups being suitably located by ligand coordination.263 An analogous process can be carried out on a thioimidate but a sulfide is formed and removal of sulfur with consequent ring contraction yields the corrin (100).264 These two complementary routes can be effected with different metal ions, nickel(II), palladium(II) and cobalt(III) in the first route, zinc(II) in the second. Removal of zinc ions easily provides the free corrin macrocycle. These two routes are summarized in Scheme 64. The sulfide contraction route was used in the Eschenmoser-Woodward total synthesis of vitamin Bn-265... 

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. 

It is of interest to compare the porphyrin and corrin macrocycles, and to consider the reactivities of porphyrin- and corrin-bound metal ions. These may be related to the size of the cavity. The corrin macrocycle provides a smaller cavity, into which cobalt fits tightly in the B12 coenzymes. Thus the cobalt does not move relative to the corrin plane, and remains coplanar with the four nitrogen donor atoms. The cobalt remains low-spin, and reactivity is controlled by the loss of the axial ligands, giving five- and four-coordinate species. 

The size of the macrocycle coordination hole has a profound influence on its coordination chemistry thus in the weak ligand field of hydroporphyrinoid systems Ni2 + assumes the high spin state and binds extra axial ligands, while in the stronger ligand field of the corrin macrocycle the coordination sphere of the metal is saturated and diamagnetic complexes are generated [82]. 

Reitzer et al., 1999) and a MeCbl-binding fragment of E. coli methionine synthase (Drennan et al., 1994), the cofactor is sandwiched between two domains (Figure 8). The conserved domain possesses an a/ 3 structure reminiscent of the Rossmann fold of nucleotide-binding proteins (Rossmann et al., 1974) and consists of a twisted )-sheet of five parallel strands encased by five a-helices. It binds the lower, a-face of the corrin macrocycle and the substituents projecting idowni from this face, notably the dimethylbenz-imidazole ribofuranosyl nucleotide loop. 

Migration of the C-11 Methyi Group to C-12 to Form the Corrin Macrocycle... 

From the structure of precorrin-4 69 and its status as substrate for the CobM enzyme, clearly a methyltransferase from its sequence, the exact function of this enzyme could be deduced. In Clostridium tetanomorphum [106-108], Pr. shermanii [109] and Ps. denitrificans [88], the order of insertion of the various methyl groups into the corrin macrocycle, after the third one in precorrin-3 A 55, had been revealed by pulse labelling and this order was the same in all three. The fourth one was placed at position 17, then at 12 a followed by 1 and, finally, 5 and 15. Precorrin-4 69 shows the C-17 methyl group in place and Sect. 3.5 reported that the 12a-methyl of the corrin system is initially inserted at C-11. It is that C-11 methylation which is blocked by deletion of the cohM gene and hence CobM is the 11 -methyltransferase of Ps. denitrificans. 

Precorrin-4 acts as the substrate for another class III methyl transferase (Figure 19), CobM, which methylates at Cl 1 to generate precorrin-5 (Figure 20). It was a surprise when this intermediate was first identified as the corrin macrocycle does not contain a methyl group at C11 but does have one at C12. In fact, as will be described later, the methyl group added to Cll is subsequently rearranged to Cl2. The reason for methylation at Cll is to allow the decarboxylation of the acetate side chain attached to C12 prior to its methyaltion but it also plays a role in permitting the function of CobF (see Section 7.13.11.5). 

The corrin macrocycle is derived biochemically from the porphyrin precursor uroporphyrinogen III [9]. However, it differs in several important respects from the porphyrin macrocycle. Perhaps the most important difference is the lack of the methene bridge between the A and D rings (carbon 20 in the porphyrin numbering system) which leads to a break in the conjugation, a loss of aromaticity, and a consequent buckling or non-planarity of the corrin macrocycle. Such buckling is readily apparent in the X-ray structure of 5 -deoxyadenosylcobalamin [10]. 

The biomethylation reaction between platinum and methylcobalamin involves both platinum(II) and platinum(IV) oxidation states. An outer-sphere complex is formed between the charged platinum(II) salts and the corrin macrocycle, which catalytically labilizes the Co—C o bond to electrophilic attack. A two-electron redox switch mechanism has been proposed between platinum(II) and platinum(IV). However, a mechanism consistent with the kinetic data is direct electrophilic attack by PtClg on the Co—C a bond in MeBu. Studies on [Pt(NH3)2(OH2)2] indicate that the bases on cobalt interact in the coordination sphere of platinum(II). Since both platinum(ll) and platinum(rV) are together required to effect methyl transfer from methylcobalamin to platinuni, Pt and C NMR spectroscopy have been used to show that the methyl group is transferred to the platinum of the platinum(n) reactant. The kinetics of demethylation by mixtures of platinum(II) and platinum(IV) complexes show a lack of dependence on the axial ligand. The authors conclude therefore that it is unlikely that the reaction involves direct attack by the bound platinum on the Co—C bond, and instead favor electron transfer from an orbital on the corrin ring to the boimd platinum group in the slow step, followed by rapid methyl transfer. ... 

As mentioned in our earlier article, the total synthesis of vitamin B12 (55) has been completed following two convergent approaches. The first of these, termed the Woodward-Eschenmoser Approach, involved construction of the corrin macrocycle (56) using classical chemistry in a joint approach by the Harvard and ETH Zurich groups.In a quite separate endeavor, the Swiss workers fashioned the corrin (56) by the new road, involving an orbital-symmetry-allowed photocyclization of a seco-corrin. 

Interestingly, the sirohydrochlorin can chelate iron to give siroheme which is the cofactor for the enz)nnes sulphite and nitrite reductase, used to reduce sulphite to sulphide and nitrite to ammonia, respectively, in certain organisms (e.g. Esherichia coif). Meanwhile, the dihydroisobacteriochlorin undergoes further methylation at the mcse-carbon C-20 to give precorrin-3. The use of the term "precorrin" was introduced by Battersby to denote intermediates on the pathway that precede the formation of the fully formed corrin macrocycle of vitamin B]2- The number suffix denotes how many C-methyl groups have been introduced into uro gen III. 

The final steps involve methylation at meso-carbons C-5 and C-15, to give precorrin-Sx followed by a [l,5]-sigmatropic shift of the methyl group from C-11 to C-12, decarboxylation of the acetic acid group at C-12, to give hydrogenobyrinic acid, and insertion of cobalt to give the completed metallo-corrin macrocycle, cobyrinic acid. 

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