Vitamin D2

The structure of vitamin D2 is the same as that of vitamin D3 except that vitamin D2 has a double bond between C 22 and C 23 and a methyl substituent at C 24... 

See also Vitamin D2 Ergosterol. [VITAMINS - VITAMIN D] (Vol 25) Ergoloid mesylate [8067-24-1]... 

Nomenclature. The Vitamin D compounds ate steroidal materials and thus ate named according to the lUPAC-IUB rules for nomenclature (1) (Table 1). Vitamin [520-91 -2] is a mixture of vitamin D2 and lumisterol. 

The common name vitamin D is used throughout the pharmaceutical kidustry for simplicity. The trivial name calciferol has also been used extensively with the prefix ergo- and chole-, which kidicate vitamin D2 (2) and vitamin (4), respectively (see Steroids). Vitamin D2 was originally named calciferol in 1931 by Angus and co-wotkets (2). Historically, a number of substances were referred to as vitamin D and were distinguished from one another by a subscript numeral, eg, vitamin D2, vitamin D, etc. 

In 1981, the lUPAC-IUB Joint Commission on Biochemical Nomenclature proposed that there be a set of trivial names for the important vitamin D compounds, including calciol [67-97-0] for vitaminD, calcidiol [19356-17-3] ion 25-hydroxy-vitaminD, and calcitriol [32222-06-3] ion 1 a,25-dihydroxy-vitamin D. This nomenclature has met with varying degrees of acceptance, as has the proposal to use calcine [69662-75-5] (deoxy-vitamin D2) and ercalcine [68323-40-0] (deoxy-vitamin D ) to name the triene hydrocarbon stmcture for 9,10-j (9-cholesta-5,7,10(19)-ttiene and... 

Windaus in 1933 derived the skeletal stmcture of vitamin D2. He found the elemental formula to be The side chain was unequivocally... 

The observation that the uv spectmm of provitamin D changed with uv inradiation and also produced antirachitic activity led to the conclusion that vitamin D was derived from the provitamin. Windaus found the vitamin D2 formula to be isomeric with the provitamins. 

Bunal in 1932 used x-ray crystallography to demonstrate that many of the preparations described in the Hterature were mixtures and that vitamin D2 was one crystal stmcture. 

Ozonolysis of vitamin D2 gave 2,3-dimethylbutanol, showing the side chain to contain the 22 double bond and a C24 methyl group. 

Vitamin D2 reacted with maleic anhydride to give a mono Diels-Alder adduct, which hydrolyzed to yield a dicarboxyhc acid. Acetylation of the alcohols, esterification of carboxyHc acids, and hydrogenation gave a compound that, when ozonized, gave a saturated ketone, This molecule... 

Irradiated ergosterol was found not to be as antirachitic in the chick as in the rat, whereas the chick could be protected by direct kradiation. The provitamin in cholesterol was shown not to be ergosterol. Rygh (14) in 1935 found that 1 rat unit of cod Hver oil was 100 times more potent in chicks than 1 rat unit of vitamin D2. Brockmann (15) in 1936, prepared the pure crystalline 3,5-dinitrobenzoate derivative of vitamin D obtained from tuna Hver oil... 

Physical Properties. The physical properties of the provitamins and vitamins D2 and are Hsted ia Table 6. The values are Hsted for the pure substances. The D vitamins are fat-soluble and, as such, are hydrophobic. 

Properties 7-Dehydro-cholesterol Ergosterol Vitamin D2 Vitamin... 

Physical Methods. Vitamins D2 and D exhibit uv absorption curves that have a maximum at 264 nm and an (absorbance) of 450—490 at 1% concentration (Table 8). The various isomers of vitamin D exhibit characteristically different uv absorption curves. Mixtures of the isomers are difficult to distinguish. However, when chromatographicaHy separated by hplc, the peaks can be identified by stop-flow techniques based on uv absorption scanning or by photodiodearray spectroscopy. The combination of elution time and characteristic uv absorption curves can be used to identify the isomers present in a sample of vitamin D. 

Infrared and nmr spectroscopy have been used to help distinguish between vitamins D2 and D (87—89). X-ray crystallographic techniques are used ... 

Direct modification of vitamin D2 or D or its metabolites to give derivatives by a variety of synthetic methods has also been used extensively (163-171). 

The metabohsm of vitamin D2 follows a pathway similar to that described for Vitamin D. ... 

Vitamin D intoxication causes 25-hydroxy vitamin blood levels to go from a normal of 30—50 ng/mL to 200—400 ng/mL. At this high level, the metabohte can compete with 1 a-25-dihydroxy vitamin for receptors in the intestine and bone and induce effects usually attributed to the dihydroxy vitamin D. Thus, 25-hydroxy vitamin is beUeved to be the critical factor in vitamin D intoxication. Vitamin D2 is metabolized slower than vitamin and thus appears to be less toxic (218). 

The metabohtes of vitamin D are usually more toxic than the vitamin because the feedback mechanisms that regulate vitamin D concentrations are circumvented. 25-Hydroxycholecalciferol has a one-hundredfold increase in toxicity over vitamin D when fed to chicks (220) and 1 a,25-dihydroxy vitamin D is several times more toxic than the 25-hydroxy analogue. Vitamin D2 seems to have less toxicity than vitamin D, a circumstance which is beheved to be caused by the more efficient elimination of 25-hydroxy and the 1 a,25-dihydroxy vitamin D2 from the animals. Estimated safe upper dietary levels are given in Table 11. 

Vitamin D is available ia a variety of forms. Cod Hver oil and percomorph Hver oil historically were good sources of vitamin D. Recent cost iacreases of these materials have caused a decline ia their market position. Cod Hver oil sold for 0.40—0.45/L ia 1970 and as high as 1.45/L ia 1979 and 3.43/L ia 1996. The prices of the cod Hver oils and of vitamin D2 and vitamin D from 1955 to 1995 are shown ia Table 12. 

Year Source Cod-hver oil, /L Ergocalciferol (crystalline vitamin D2), /g Cholecalciferol D /g... 

The vitamin D2 volume is estimated at only 1200 kg/yr, exclusive of Chinese sources. 

An especially important case is the thermal equilibrium between precalciferol (pre-vitamin Dj, 22) and calciferol (vitamin D2, 23). ... 

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