22- Dehydrocholesterol

A steroid very closely related structurally to cholesterol is its 7 dehydro derivative 7 Dehydrocholesterol is formed by enzymatic oxidation of cholesterol and has a conju gated diene unit m its B ring 7 Dehydrocholesterol is present m the tissues of the skin where it is transformed to vitamin D3 by a sunlight induced photochemical reaction... 

See also 7-Dehydrocholesterol Cholecalciferol. [VITAMINS - VITAMIN D] (Vol 25) -See also 22,23-Dihydroergosterol. [VITAITINS - VITAMIN D] (Vol 25)... 

Infants maybe sensitive to doses of vitamin A [11103-57-4] in the range of 75,000—200,000 lU (22.5—60 mg), although the toxic dose in adults is probably 2—5 million lU (90.6—1.5 g). Intakes in this range from normal food suppHes without oral supplements are simply beyond imagination (79). Vitamin D [1406-16-2] toxicity is much more difficult to substantiate clinically. Humans can synthesize active forms of the vitamin in the skin upon irradiation of 7-dehydrocholesterol. Toxic symptoms are relatively nonspecific, and dangerous doses seem to He in the range of 1000—3000 lU/kg body wt (25—75 flg/kg body wt) (80). Cases of toxicity of both vitamins E and K have been reported, but under ordinary circumstances these vitamins are considered relatively innocuous (81). 

Vitamins are classified by their solubiUty characteristics iato fat-soluble and water-soluble groups. The fat-soluble vitamins A, E, and K result from the isoprenoid biosynthetic pathway. Vitamin A is derived by enzymic cleavage of the symmetrical C q beta-carotene, also known as pro-vitamin A. Vitamins E and K result from condensations of phytyldiphosphate (C2q) with aromatic components derived from shikimic acid. Vitamin D results from photochemical ring opening of 7-dehydrocholesterol, itself derived from squalene (C q). 

Vitamin (cholecalcifetol calciol), (5Z,7E)-(33)-9,10-seco-5,7,10(19) cholestatriene-3-ol (4), is the naturally occurring active material found ki all animals. It is produced ki the skin by the kradiation of stored 7-dehydrocholesterol (provitamin E) ), cholesta-5,7-diene-3B-ol (3). 

Windaus and Boch (13) isolated and characterized 7-dehydrocholesterol in 1937 from pig skin. They further showed that vitamin D could be generated from the provitamin by uv inradiation. 

P-Hydroxy steroids which contain the 5,7-diene system and can be activated with uv light to produce vitamin D compounds are called provitamins. The two most important provitamins are ergosterol (1) and 7-dehydrocholesterol (3). They are produced in plants and animals, respectively, and 7-dehydrocholesterol is produced synthetically on a commercial scale. Small amounts of hydroxylated detivatives of the provitamins have been synthesized in efforts to prepare the metaboHtes of vitamin D, but these products do not occur naturally. The provitamins do not possess physiological activities, with the exception that provitamin D is found in the skin of animals and acts as a precursor to vitamin D, and synthetic dihydroxalated... 

Dehydrocholesterol has also been made from cholesterol by the Windaus procedure (Pig. 2) the 3,7-dibenzoate (16) is obtained (via (14) and (15) by oxidation and reduction), which undergoes thermal elimination to give the 7-dehydrocholesteryl benzoate (11) (42—44). However, the yields are substantially lower than those achieved by the brornination—dehydrobrornination method. 

Tosylhydra2one and 7-phenyl sulfoxide groups have also been introduced into cholesterol and eliminated to prepare the 5,7-diene (45,46). The method of choice is the aHyUc brornination—dehydrobrornination procedures, and the commercial yields ia converting cholesterol to 7-dehydrocholesterol are ia the range of 35—50%. 

The molecular extinction coefficients (at various wavelengths) of the four main components of the irradiation are shown in Table 5. The absorption of light above 300 nm is favored by tachysterol. A yield of 83% of the previtamin at 95% conversion of 7-dehydrocholesterol can be obtained by irradiation first at 254 nm, followed by reirradiation at 350 nm with a yttrium aluminum garnet (YAG) laser to convert tachysterol to previtamin D. A similar approach with laser irradiation at 248 nm (KrF) and 337 nm (N2) has also been described (76). 

Provitamin D. The molecular extinction coefficient of 7-dehydrocholesterol at 282 nm is 11,300 and is used as a measure of 7-dehydro isomer... 

A flow diagram for the manufacturing process is shown in Figure 8. First, ether solution containing 7-dehydrocholesterol is recirculated through a quartz uv reactor, and the ether is distilled off. Methanol is added to the 7-dehydrocholesterol—vitarnin mixture, and the remaining ether is... 

Photochemical ting opening of 7-dehydrocholesterol derivatives which have ting A or the side chain modified (142,143). 

FIGURE 18.37 (a) Vitamin D3 (cholecalciferol) is produced in the skin by the action of sunlight on 7-dehydrocholesterol. The successive action of mixed-function oxidases in the liver and kidney produces 1,25-dihydroxyvitamin D3, the active form of vitamin D. 

Actually, neither vitamin D2 nor D3 is present in foods. Rather, foods contain the precursor molecules 7-dehydrocholesterol and ergosterol. In the presence of sunlight, however, both precursors are converted under the skin to the active vitamins, hence the nickname for vitamin D, the "sunshine vitamin. 7... 

Ullmanns Encykl. Tech. Chem., 3. Aufl., Vol. 18, 236 ff. (synthesis of 7-dehydrocholesterol as described). 

Figure 42-9. Formation and hydroxylation of vitamin D3.25-Hydroxylation takes place in the liver, and the other hydroxylations occur in the kidneys. 25,26(OH)2-D3 and 1,25,26(OH)3-D3 are probably formed as well. The formulas of 7-dehydrocholesterol, vitamin D3, and 1,25(OH)2-D3 are also shown. (Modified and reproduced, with...

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