Corrinoid synthesis

By adding a cell extract of the parental strain P. shermanii to the culture of 30 the synthesis of vitamin Bn was restored, although incompletely. The activity of ALA synthetase and ALA dehydratase in the strain 30 was not reduced, the rate of PBG synthesis was normal, therefore, the block in corrinoid synthesis occurred at a step distal to PBG formation, where the pathways of porphyrin and corrinoid synthesis diverge. It should be noted that the ratio of propionic to acetic acid in negative mutants remained in the range of 2 1 formic acid was produced only by two cultures, 30 and rough. Mutant 9 produced a low level of acetic acid, and volatile acids were represented basically by propionic acid alone. 

Vitamin Bn-deficient cells contained about 30-45% less DNA than cells with physiological levels of the vitamin (Vorobjeva and Iordan, 1976 Iordan, 1992). The DNA content in these cells increased by up to 80% when AdoCbl was added to cultures growing in cobalt-ffee medium (Iordan et al., 1983) (Table 5.1). Strains with a potential capacity for high corrinoid synthesis demonstrated a more significant stimulation by exogenous AdoCbl than strains with low synthetic capacity (Fig. 5.7). However, P. acnes represented an exception to this rule it responded weakly to the addition of AdoCbl, despite having a high potential for vitamin Bn synthesis. 

A second synthesis of cobyric acid (14) involves photochemical ring closure of an A—D secocorrinoid. Thus, the Diels-Alder reaction between butadiene and /n j -3-methyl-4-oxopentenoic acid was used as starting point for all four ring A—D synthons (15—18). These were combined in the order B + C — BC + D — BCD + A — ABCD. The resultant cadmium complex (19) was photocyclized in buffered acetic acid to give the metal-free corrinoid (20). A number of steps were involved in converting this material to cobyric acid (14). 

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... 

Corrinoid iron-sulfur protein (CFeSP) purified and characterized acetyl-CoA synthesis reconstituted from CH3-H4 folate, CO, and CoA using purified proteins. ... 

Fig. 11. Active sites and reactions of the bifunctional CODH/ACS. For synthesis of acetyl-CoA, two electrons are transferred from external electron donors to Cluster B of the CODH subunit. Electrons are relayed to Cluster C which reduces CO2 to CO. The CO is proposed to be channeled to Cluster A of the ACS subunit to form a metal-CO adduct that combines with the methyl group of the CFeSP and CoA to form acetyl-CoA. For utilization of acetyl-CoA, these reactions are reversed. The abbreviations are CODH, CO dehydrogenase ACS, acetyl-CoA synthase CFeSP, the corrinoid iron-sulfur protein CoA, Coenzyme A.

The third reason for favoring a non-radical pathway is based on studies of a mutant version of the CFeSP. This mutant was generated by changing a cysteine residue to an alanine, which converts the 4Fe-4S cluster of the CFeSP into a 3Fe-4S cluster (14). This mutation causes the redox potential of the 3Fe-4S cluster to increase by about 500 mV. The mutant is incapable of coupling the reduction of the cobalt center to the oxidation of CO by CODH. Correspondingly, it is unable to participate in acetate synthesis from CH3-H4 folate, CO, and CoA unless chemical reductants are present. If mechanism 3 (discussed earlier) is correct, then the methyl transfer from the methylated corrinoid protein to CODH should be crippled. However, this reaction occurred at equal rates with the wild-type protein and the CFeSP variant. We feel that this result rules out the possibility of a radical methyl transfer mechanics and offers strong support for mechanism 1. 

Lenhert and Hodgkin (15) revealed with X-ray diffraction techniques that 5 -deoxyadenosylcobalamin (Bi2-coenzyme) contained a cobalt-carbon o-bond (Fig. 3). The discovery of this stable Co—C-tr-bond interested coordination chemists, and the search for methods of synthesizing coen-zyme-Bi2 together with analogous alkyl-cobalt corrinoids from Vitamin B12 was started. In short order the partial chemical synthesis of 5 -de-oxyadenosylcobalamin was worked out in Smith s laboratory (22), and the chemical synthesis of methylcobalamin provided a second B 12-coenzyme which was found to be active in methyl-transfer enzymes (23). A general reaction for the synthesis of alkylcorrinoids is shown in Fig. 4. 

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... 

The reaction [Eq. (7)] requires a disulfide-reducing system such as dithiothreitol or disulfide reductase and a reducing agent such as NADPH or reduced ferredoxin. It is proposed [Eq. (5)] that carbon monoxide oxidoreductase binds CO as a one-carbon intermediate [C,], which can be either oxidized to C02 or condensed with the methyl group of a methylated corrinoid protein and CoA in the final step of acetyl-CoA synthesis. 

SYNTHESIS AND SOME REACTIONS OF PHTHALOCYANINE, PORPHINOID AND CORRINOID 192 MACROCYCLES... 

A consideration of the synthesis and reactions of phthalocyanines, porphinoids, corrinoids and related macrocycles will follow in the second section. Discussion in this section will be restricted because these topics will receive consideration in other chapters. 

Metal-free corrinoids are produced by photosynthetic bacteria.863 This allows the synthesis of analogues of vitamin B12 having other metals present, such as zinc, copper or rhodium. The... 

This section will not be concerned with the detailed description of the synthetic methods leading to the appropriate precursors we will limit our attention to the crucial step of the synthesis of corrinoids, i.e. the formation of the tetrapyrrolic ring. The corrinoid macrocycle has been synthesized following two different procedures the first one involves the cyclization of a proper linear precursor, while the second involves ring contraction of a porphyrinoid structure. 

The second article deals with the synthesis and properties of metal correlates and corrinoids. In view of the many articles written on corrinoids, the correlates are in the foreground of the article, adetailed discussion oftheir structures, of their IR-, UV/Vis-, photoelectron-, and NMR spectra, and of their electrochemical behavior being given. Sylvia Licoccia is Professor of Chemistry at the University of Rome Tor Vergata and has not only made notable scientific contributions to corrole chemistry, butto porphyrin chemistry as well. 

The complexes of octaphenyltetraazaporphyrin were obtained by heating (270-280°C) diphenylmaleinodinitrile and metal chlorides (MC1 n = 3, 4 M = Ga, In, V, Lu, Sn, Ti, Zr) [335], We note that the application of template synthesis allowed us to obtain the vitamin B12 and a series of other metal-corrinoide systems [318,336], The template syntheses found application to prepare ICC of Schiff bases and their analogues with coordination units MN4 (3.156) [337-339] ... 

Vitamin B12 has been successfully synthesized (W2), but this was a major undertaking involving 100 people over 11 years. The synthesis was completed in two stages first, the corrinoid cobyric acid, which is a natural substance, was converted to vitamin B12, then work was continued on the synthesis of the cobyric acid. The procedure is complex and still not of commercial significance. However, the synthesis of such a complex molecule was a great achievement at the time. 

Menon, S., and Ragsdale, S. W., 1998, Role of the [4Ee64S] cluster in reductive activation of the cobalt center of the corrinoid iron-sulfur protein from Clostridium thermoaceticum during acetyl-CoA synthesis Biochem. 37(16) 5689n5698. 

ACS catalyzes the synthesis of acetyl-CoA from CO, CoA, and a methyl group donated by a methylated corrinoid iron sulfur protein (Reaction 4, Table 1). In the CODH-only enzymes like CODHI and II from C hydrogenoformans and R. rubrum, there is evidence for a channel between the surface and the C-cluster (above). On the other hand, in CODH/ACS,... 

Microbial synthesis of porphyrins and corrinoids 87MI50 89MI6. Molecular recognition of porphyrin 89YGK514. 

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