Corrinoids structures

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... 

One of the structures present in many enzymes is the corrinoid structure. It consists of a tetrapyrrolic macrocycle, where a direct link between two pyrrole rings exists. Such a direct link and the different degrees of unsaturation that can be introduced into the macrocycle modulate its chelating properties towards metal ions and its reactivity. 

A most interesting example of the corrinoid structure is corrole, a macrocycle where an 18 electron aromatic it system analogous to that of a porphyrin is maintained. Corrole has been shown to be a versatile ligand capable of coordinating transition and main group metals without significant distortion of the macrocycle plane. 

In the laboratory, as well as in Nature, corrinoid macrorings must be constructed from pyrroles. The complicated substitution patterns and the various unsaturation levels that can be introduced in the corrinoid structures represented a serious problem for the organic synthetic chemists and have stimulated many investigations in the past. 

This method affords the macrocycle by final formation of the direct link between pyrroles A and D from an appropriate linear tetrapyrrole. The proper reduced bilin must be synthesized in order to have a specific substitution pattern of the corrinoid structure. 

Another example of a ring contraction reaction leading to a corrinoid structure is the preparation of a,p,y-triazatetrabenzcorrole [83] the formula of which is reported in Fig. 30. This new macrocyclic ring has been isolated as its Ge4+ derivative formed by the ring-contractive reaction of germanium phthalo-cyanine carried out in the presence of NaBH4 or H2Se. 

It is suggested that the nickel is bound to a low molecular weight factor, different from F430 of methanogens, and which may involve a corrinoid structure. The nickel is thought to cycle between Ni and Ni , with the CO bound to the metal. ESR data have been interpreted in terms of an Ni species with a bound radical derived from either CO or CO2. The involvement of a nickel-carbon bond has been unequivocally established by isotopic substitution (which is shown in the g = 2.08, 2.02 signals). About 40% of the total nickel is present as this species, suggesting that the Ni—C species is a viable intermediate in the catalytic conversion of CO to CO2. There are parallels with industrial and laboratory catalytic processes, but the involvement of Ni seems... 

Fig. 4. Attachment of the deoxyadenosyl group to the cobalt of the corrinoid structure.

The corrinoids involved in methyl group transfer do not possess the organo-ligand 5 -deoxyadenosyl [see structure (II), Section I,B] and the reaction probably proceeds via the intermediate formation of the methyl cobalt complex, but no mechanistic details have yet been established. 

The similarity between the structures of the corrinoids and the porphyrins becomes evident from comparison of cobyrinic acid (75) (the simplest of the corronoids so far isolated) with uroporphyrinogen III (70). The possibility of a biosynthetic relationship between these structures was suggested by Shemin, who reported the incorporation of [14C]ALA into vitamin Bn and confirmed by the subsequent demonstration that PBG was also incorporated. The ubiquitous precursorial role of uroporphyrinogen III in heme, chlorophyll and corrinoid biosynthesis proposed by Porra (65BBA(107)176) was, however, not substantiated by experimental evidence until much later, when under carefully controlled conditions cells of Propionibacterium shermanii were shown to incorporate radioactivity from [14C]uroporphyrinogen III into vitamin Bn (72JA8269). 

The structure of factor III, the trimethyl isobacteriochlorin, is worthy of note. Preliminary studies had suggested the structure (81), which was in better accord with a subsequent ring contraction to the corrinoid skeleton involving oxidation at C-20 followed by extrusion of formaldehyde. However, the 13C NMR spectrum of factor III (as its octamethyl ester) enriched biosynthetically with [13CH3]methionine and [5-13C]ALA (Scheme 25) shows both the meso and meso- methyl carbons as doublets, a feature in accord with substitution of... 

This group of compounds is widely found in nature as metal complexes in the chlorophylls, the haem groups of many iron proteins and the corrinoids. They have in common a macrocyclic structure which provides four N donor atoms at the comers of a square plane. Metal coordination to the N atoms results in the displacement of two H+ ions. An extremely important feature of these molecules is their extensive -electron delocalization. The complexation of these and synthetic analogues has been the subject of a number of texts.143-145 Some of these aspects are also covered by Dolphin (Chapter 21,1), and biological related properties by Hughes (Chapter 62.1). 

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... 

In these compounds the cobalt atom is enclosed in a highly conjugated cobalamin structure and linked to an alkyl group via a metal-carbon bond. The B12 coenzymes are diamagnetic and can be regarded as complexes of cobalt(III) with a carbanion as a ligand (2). As this review will be limited to cases of direct metal-protein interactions the corrinoids will not be discussed further. 

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

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 cyclization reaction can be carried out in different conditions depending on the oxidation level of the desired corrinoid. Now all members of the family of such tetrapyrroles are available. Their structures have been reported in Fig. 7 and a list of the abbreviations used for the different ligands is reported in Sect. 2.3. 

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 synthetic procedures leading to corrinoid metal complexes have been developed in order to use them as models of the biosynthetic pathway to Vitamin B12. Their chemical and structural properties were expected to be very similar to those of the natural coenzyme and this is probably the reason why very few detailed investigations on their spectroscopic or electrochemical features and their reactivity towards axial coordination have been carried out. 

Another structural variation operated in these compounds is the substitution at the angular 1,19-positions with methyl groups in natural corrinoids only the 1 postion is substituted. Such alteration is necessary on one hand because the cobalt complex of 1-methyl-octadehydrocorrin is unstable and, on the other hand, the related [Co(A2TDC)]+ is prepared by reduction of [Co(A2ODC)] + [2]. 

Although the basic structure of these synthetic species is very similar to that of the natural corrinoids their reactivity shows several differences thus [Co(A2ODC)] + does not form an adduct with dioxygen or give organometallic derivatives, which are characteristic features of the chemistry of Vitamin B12 and related compounds [13]. This failure has been attributed to a different electronic structure, as confirmed by the very different optical spectra of the two systems (Fig. 32). 

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. 

Electronic Structure of Vitamin B12 Corrinoids Vitamin B12 is a complex molecule and its activation pathway is not fully understood. Research using UV-vis, resonance Raman, circular dichro-... 

---