Cyanocobalamine

Cyanobond Cyanoborohydride Cyanocarbon acids Cyanocarbon anions Cyanocarbons Cyanocobalamin... 

The structure of the first isolated vitamin cyanocobalamin [68-19-9] (la) is known to occur only sporadically, at best, in biological systems. Its isolation... 

The lUPAC-IUB Commission on Biochemical Nomenclature (13) recommends that the term vitamin B 2 be used as the genetic descriptor for aU. cottiaoids exhibiting quaUtatively the biological activity of cyanocobalamin. However, because of its commercial importance, cyaaocobalamin is used iaterchangeably with vitamin B 2 heteia. 

Table 3. Physical and Chemical Properties of Vitamin (Cyanocobalamin) ...

Specifications. Cyanocobalamin is the commercial form of vitamin It is sold under the following tradenames (35) ... 

Various aspects of the chromatography of vitamin B 2 and related corrinoids have been reviewed (59). A high performance Hquid chromatographic (hplc) method is reported to require a sample containing 20—100 p.g cyanocobalamin and is suitable for premixes, raw material, and pharmaceutical products (60). 

The total syntheses have yielded cobyric acid and thence cyanocobalamin. Routes to other cobalamins, eg, methylcobalamin and adenosylcobalamin, are known (76—79). One approach to such compounds involves the oxidative addition of the appropriate alkyl haUde (eg, CH I to give methylcobalamin) or tosylate (eg, 5 -A-tosyladenosine to yield adenosylcobalamine) to cobalt(I)alamine. 

Commercial Production. Vitamin B22, as cyanocobalamin, is produced by several companies. The market is dorninated, however, by two... 

Market Forms. Vitamin B 2 is sold almost exclusively as cyanocobalamin. Approximately one-third of the material is for the human pharmaceutical market whereas two-thirds is used in the animal feed market, primarily for poultry and swine (see Feeds AND FEED ADDITIVES). Modest growth in both markets has occurred in the period 1980—1995 and this trend is expected to continue. 

Cobalt is one of twenty-seven known elements essential to humans (28) (see Mineral NUTRIENTS). It is an integral part of the cyanocobalamin [68-19-9] molecule, ie, vitamin B 2> only documented biochemically active cobalt component in humans (29,30) (see Vitamins, VITAMIN Vitamin B 2 is not synthesized by animals or higher plants, rather the primary source is bacterial flora in the digestive system of sheep and cattle (8). Except for humans, nonmminants do not appear to requite cobalt. Humans have between 2 and 5 mg of vitamin B22, and deficiency results in the development of pernicious anemia. The wasting disease in sheep and cattle is known as bush sickness in New Zealand, salt sickness in Florida, pine sickness in Scotland, and coast disease in AustraUa. These are essentially the same symptomatically, and are caused by cobalt deficiency. Symptoms include initial lack of appetite followed by scaliness of skin, lack of coordination, loss of flesh, pale mucous membranes, and retarded growth. The total laboratory synthesis of vitamin B 2 was completed in 65—70 steps over a period of eleven years (31). The complex stmcture was reported by Dorothy Crowfoot-Hodgkin in 1961 (32) for which she was awarded a Nobel prize in 1964. 

FIGURE 18.28 The structure of cyanocobalamin (top) and simplified structures showing several coenzyme forms of vitamin Bi2- The Co—C bond of 5 -deoxyadenosylcobalamin is predominantly covalent (note the short bond length of 0.205 nm) but with some ionic character. Note that the convention of writing the cobalt atom as Co" " attributes the electrons of the Co—C and Co—N bonds to carbon and nitrogen, respectively. 

Conversion of inactive vitamin Bj2 to active 5 -deoxyadenosylcobal-amin is thought to involve three steps (see figure). Two flavopro-tein reductases sequentially convert Co in cyanocobalamin to the Co state and then to the Co state. Co is an extremely powerful nucleophile. It attacks the C-5 carbon of ATP as shown, expelling the triphosphate anion to form 5 -deoxyadenosyl-... 

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