Vitamin Bi2 derivatives

FIGURE 5-14 Structures of some chemical species useful for designing anion-selective electrodes (a) Mn(III) porphyrin (b) vitamin Bi2 derivative (c) tri-n-octyltin chloride (d) lipophilic polyamine macrocyclic compound. 

Potential applications of vitamin Bi2 in electrocatalytic degradation of dibromide and a-haloacetic acid pollutants has been demonstrated in aqueous buffers303,304 and in surfactant-stabilized emulsions.305 Electroreductive dehalogenations in water and microemulsions were also efficiently catalyzed by a vitamin Bi2 derivative grafted onto a polylysine-coated electrode.306... 

Cobaloxime(I) generated by the electrochemical reductions of cobaloxime(III), the most simple model of vitamin Bi2, has been shown to catalyze radical cyclization of bromoacetals.307 Cobalt(I) species electrogenerated from [ConTPP] also catalyze the reductive cleavage of alkyl halides. This catalyst is much less stable than vitamin Bi2 derivatives.296 It has, however, been applied in the carboxylation of benzyl chloride and butyl halides with C02.308 Heterogeneous catalysis of organohalides reduction has also been studied at cobalt porphyrin-film modified electrodes,275,3 9-311 which have potential application in the electrochemical sensing of pollutants. 

The number of vitamin B 12-dependent reactions is not large. Most of these involve rearrangements of the carbon skeletons of metabolites. Such reactions are important in linking some aspects of fatty acid metabolism to the citric acid cycle. In another form, a vitamin Bi2-derived coenzyme is involved, along with folic acid coenzymes, in the metabolism of one-carbon fragments, including the biosynthesis of methionine. 

The enzymes involved are reported to use either A-adenosylmethionine or vitamin Bi2 derivatives as methyl donors, and in addition to mercury, the metals, lead, tin,... 

Kunkely H, Pavlovski V, Vogler A. Photochemistry of vitamin Bi2 derivatives. New observations and conclusions, in contributions to development of coordination chemistry. In Ondrejovic G, Sirota A, eds. Proceedings of the 14th International Conference on Coordination Chemistry. Bratislava Slovak Technical University Press, 1993 363. 

Cobalt is present in human organisms in the form of vitamin Bi2 derivatives, and the physiological actions of NO on vitamin Bi2 derivatives were intensively studied (54). It was reported that the reduced form of vitamin B12, [Cbl(II)], reacts with gaseous NO to form a stable nitrosyl complex. 

Under physiological conditions vitamin Bi2-derivatives have been observed in three different oxidation states, Co(ni), Co(II), and Co(I), each possessing different coordination properties and quahtatively differing reactivities [22, 75]. Oxidation-reduction processes are therefore of key importance in the chemistry and biology of B12. Electrochemical methods have been apphed in the synthesis of organometallic B 12-derivatives [86,87], as well as for the purpose of generating reduced forms of protein boxmd B -derivatives [88] and electrode-boimd B -derivatives for analytical apphcations [89]. 

Synthesis of the L. leichmannii reductase is derepressed under particular culture conditions in which minimal amounts of vitamin Bi2 derivatives are provided. Under such conditions, the aporeductase is produced in amounts which greatly exceed the amount of the Bu cofactor present in the bacterial cells. Purification procedures developed for the reductase utilized cells derepressed in this way and yielded the highly purified apoen-zyme 25) the holoenzyme was not isolated in these procedures. The isolation of the inactive aporeductase made possible the demonstration of its absolute requirement for a vitamin Bu cofactor 5 -deoxyadenosylcobala-min, the most abundant corrinoid in L. leichmannii 26), binds very tightly to the aporeductase and, therefore, appears to be the natural cofactor. The highly purified reductase accepts as substrates only ribonucleoside inphosphates, in contrast to the requirement of the E. coli enzyme for diphosphates. A single enzyme reduces ATP, GTP, UTP, or CTP the... 

Although X-ray crystallography provided most of the detailed structural information on cobalt-corrins in the crystal (15-17), NMR spectroscopic studies have contributed to the characterization of vitamin B12 derivatives in solution and have made possible the structural characterization of noncrystallizable vitamin Bi2 derivatives, such as neocoenzyme B12, an epimer of coenzyme B12 (2, AdoCbl) (27). Such studies revealed the organometallic ligands of AdoCbl and of related organometallic B12 derivatives to be bound to the cobalt center in a conformationally flexible way (22,23). 

As for the model studies of the coenzyme Bi2 catalyzed methylmalonyl to succinyl rearrangement, the interaction between a vitamin Bi2 derivative containing a peripheral Cjg aUcyl chain and a (methyl)thiomalonate substrate bearing long alkyl chains at the thioester group was effectively used for electrolysis under photoirradiation (see Fig. 4). The electrolysis of thioesters at —0.85 V versus SCE in Me0H/H20 (v/v, 4 1) in... 

Hisaeda Y, Nishioka T, Inoue Y, Asada K, Hayashi T (2000) Electrochemical reactions mediated by vitamin Bi2 derivatives in organic solvents. Coord Chem Rev 198 21-37... 

Schemes 3-7 describe the synthesis of cyanobromide 6, the A-D sector of vitamin Bi2. The synthesis commences with an alkylation of the magnesium salt of methoxydimethylindole 28 to give intermediate 29 (see Scheme 3a). The stereocenter created in this step plays a central role in directing the stereochemical course of the next reaction. Thus, exposure of 29 to methanol in the presence of BF3 and HgO results in the formation of tricyclic ketone 22 presumably through the intermediacy of the derived methyl enol ether 30. It is instructive to point out that the five-membered nitrogen-containing ring in 22, with its two adjacent methyl-bearing stereocenters, is destined to become ring A of vitamin Bi2. A classical resolution of racemic 22 with a-phenylethylisocyanate (31) furnishes tricyclic ketone 22 in enantiomerically pure form via diaster-eomer 32.

Vitamin B12 derivatives are also effective catalysts for the electroreductive cyclization of bromoalkenes in conductive microemulsions,299 300 or for ring-expansion reactions in cyclic a-(bromomethyl)-(3-keto esters in DMF.301 Vitamin Bi2 attached to an epoxy-polymer has been used in electrosynthesis of valeronitrile by reductive coupling of iodoethane and acrylonitrile.302... 

Vitamin Bi2 is a D-ribofuranose derivative, and the structure of vitamin B12 5 -phosphate, a precursoi 11 of vitamin B12, has been determined. The a-D-glycosidic bond lies 16° (0.51 A) out of the plane of the 5,6-dimethylbenzimidazole ring, because of steric or nonbonded interactions. The D-ribofuranose moiety has that envelope conformation having C-2 exo (0.77 A exoplanar) C-3 and C-5 bear phosphate groups. 

Vitamin B12 consists of a porphyrin-like ring with a central cobalt atom attached to a nucleotide. Various organic groups may be covalently bound to the cobalt atom, forming different cobalamins. Deoxyadenosylcobalamin and methylcobalamin are the active forms of the vitamin in humans. Cyanocobalamin and hydroxocobalamin (both available for therapeutic use) and other cobalamins found in food sources are converted to the active forms. The ultimate source of vitamin Bi2 is from microbial synthesis the vitamin is not synthesized by animals or plants. The chief dietary source of vitamin Bi2 is microbially derived vitamin B12 in meat (especially liver), eggs, and dairy products. Vitamin Bi2 is sometimes called extrinsic factor to differentiate it from intrinsic factor, a protein normally secreted by the stomach that is required for gastrointestinal uptake of dietary vitamin B12. 

Interestingly, it is possible to isolate derivatives of vitamin Bj2 which lack the cobalt atom (65PNA(54)934, 70BBR(39)170>, and this has led to some speculation that insertion of cobalt may be one of the final steps in the biosynthesis of vitamin Bi2. 

Porphyrins and chlorophylls are the most widespread natural pigments. They are associated with the energy-converting processes of respiration and photosynthesis in living organisms, and the synthesis of specific porphyrin derivatives is often motivated by the desire to perform similar processes in the test tube. The structurally and biosynthetically related corrins (e.g. vitamin BI2) catalyze alkylations and rearrangements of carbon skeletons via organocobalt intermediates. The biosyntheses of these chromophores are also of topical interest. 

The thermal stability of benzylcobalamin is significantly lower than that of the benzyl derivatives of various other cobalt complexes for example [C6H5CH2—Co(DMGH)2(py)] and [C6H5CH2— Co(CN)5]3, that have been invoked as vitamin Bi2 models (9, 10, 12, 13). 

The reaction of a Co(I) nucleophile with an appropriate alkyl donor is used most frequently for the formation of a Co-C bond, which also can be formed readily by addition of a Co(I) complex to an acetylenic compound or an electron-deficient olefin (5). The nu-cleophilicity of Co(I) in Co(I)(BDHC) is expected to be similar to that in the corrinoid complex, as indicated by their redox potentials. The formation of Co-C a-bond is the attractive criterion for vitamin Bi2 models. Sodium hydroborate (NaBH4) was used for the reduction of Co(III)(CN)2(BDHC) in tetrahydrofuran-water (1 1 or 2 1 v/v). The univalent cobalt complex thus obtained, Co(I)(BDHC), was converted readily to an organometallic derivative in which the axial position of cobalt was alkylated on treatment with an alkyl iodide or bromide. As expected for organo-cobalt derivatives, the resulting alkylated complexes were photolabile (17). 

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