Provitamin D3

Whether the synthesis or storage of provitamin D3 can occur in the human is uncertain, but it can certainly occur in animals. Glover et al. (G3) have shown that this provitamin is present in the tissues even when the animals are fed on a practically sterol-free diet. The conclusion is reached that the animal is not dependent on dietary provitamin D but has the power to synthesize it from cholesterol. The small intestine is especially rich in provitamin. The same authors noted that, in the guinea pig, infection of the liver with Pasteurella pseudotuberculosis is associated with an increased concentration of provitamin in the intestinal mucosa, an interesting observation in view of the possible role of infection in idiopathic hypercalcemia in infancy. 

The skin has a well-documented role in vitamin D metabolism. 7-Dehydrocho-lesterol (provitamin D3) is activated by exposure to ultraviolet radiation in the skin to previtamin D3, which isomerizes to vitamin D3. Recently, further metabolism of 24,25-dihydroxyvitamin D to biologically active 1,25-dihydroxy vitamin D has also been demonstrated in skin, a conversion previously assumed to occur only in the kidney. 

Vitamin D3 is not an essential exogenous micronutrient as such because it is made endogenously from a precursor in skin, 7-dehydrocholesterol (provitamin D3), by exposure to the high-energy ultraviolet B (UVB) photons (290-315 nm) of the solar spectrum [33]. The photons penetrate the epider-... 

Vitamin D, (1) is an essential factor for the life of animals and man. It is formed in the skin under the influence of UV light from provitamin D3 (2) and is one of the most important regulators of calcium metabolism. For instance, children lacking vitamin D develop rickets and adults suffer from osteoporosis. 

Cycloaddition of 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione to provitamin D3 affords exclusively the product formed by addition to the least hindered a-face of the more reactive diene, the structure was determined by X-ray8. The diastereoselectivity appears to be determined by the steric effect of the rran.v-hydrindane system, although the mechanism has not been elucidated. The cycloaddition of 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione was exploited to temporarily protect the diene group in the syntheses of la-hydroxy vitamin D3 7 a(X = H)8,9 and la,25-dihydroxy vitamin D3 7b (X = OH, starting from 25-hydroxy provitamin D3)10. Complete stereocontrol was observed in the cycloreversion step. For related cycloadditions to vitamin D3 see Section 7.2,10.3.4. 

Does the [1,7] sigmatropic rearrangement that converts provitamin D3 to vitamin D3 involve suprafacial or antarafacial rearrangement ... 

Explain why photochemical ring closure of provitamin D3 to form 7-dehydrocholesterol results in the hydrogen and methyl substituents being trans to one another. 

Further products have been identified from the irradiation of 7-dehydro-cholesterol [(130), provitamin D3]. In ether or alcohol the main component of the photolysate was assigned structure (131) which results from the photochemical cyclization of the trans-Z-cis-conformation of the triene (132) formed by ringopening of the cholesterol.92 From reaction in ethanol two alcohol-addition products (133) and (134) have been identified. Two other products of the toxisterol type have been assigned structures (135), the difference between them... 

Work on the stmctural relationships between provitamin D3 (la) and vitamin D3 (7a), and between provitamin D2 (lb) and vitamin D2 (7b) had to await the conclusive determination in 1932 of the structure of the parent compound cholesterol ) Scheme 1). 

Vitamin D3 (7a) is obtained commercially by partial synthesis. This partial synthesis begins with inexpensive cholesterol and its transformation into provitamin D3 (la). It ends with light-induced ring opening to previtamin D3 (5a) and its thermally induced 1,7-H-shift to vitamin D3 (7a, see Scheme 3). Since 5 reacts back to 1 and onwards to 2 and 6, the result is a photostation-ary mixture. UV Irradiation of 1 is expediently carried out at 0°, to largely exclude isomerization of 5 into 7. This is important for the prevention of further reaction of 7 into the so-called over-irradiation products ), the components of which would appreciably raise the diversity of the irradiated mixture. 

Chemical structure (Figure 3). 7-Dehydrocholes-terol (provitamin D3) converted to cholecalciferol by UV irradiation enzymatic hydroxylation to 25-OH-cholecalciferol in liver enzymatic hydroxylation to la,25(OH)2 colecalciferol in kidney. 

Early investigators showed that superficially purified cholesterol and activatable foods contained a provitamin, or precursor, which was converted into the vitamin on irradiation. Ultimately, two vitamin D precursors were identified. Provitamin D2 was found to be ergosterol (la). WiNDHAUS 194) and Askew (6) independently isolated pure crystalline vitamin D2 (2 a) via its 3,5-dinitrobenzoate from the complex and unstable irradiation products of ergosterol. Provitamin D3 was more difficult to identify, but it was found by Windhaus 195) to be 7-dehydro-cholesterol (lb). On irradiation crystalline vitamin D3 (2b) was obtained, which was identical with that isolated from tuna-liver oil by Brock-MANN 29). Vitamins D4 and D5 have been found in nature, each one differing from the other and the ones mentioned above in the constitution of the side chain. 

Straying, J. Compounds Related to Provitamin D3. IV. 3-Methylcholesterol and the Corresponding Provitamin. Rec. Trav. Chim. Pays-Bas 71, 822 (1952). 

Scheme 12.7 Improved synthesis of vitamin D3. Tachysterol is formed in equilibrium with provitamin D3 in the photochemical microreactor (2 313-578 nm) and conversion to vitamin D3 is achieved in a further thermal/photochemical microreactor (2 360 nm, 100 °C). Reprinted with permission from [19]...

Like the other fat-soluble vitamins, vitamin D is found in more than one form and of these the two most important are cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). They occur largely as inactive provitamins which are converted into the active forms on exposure to ultraviolet light. The provitamins are both sterols and the effect of irradiation is to open the B ring this means that the vitamins themselves are not sterols. Provitamin D3 or 7-dehydro-cholesterol is present in the unsaponifiable fraction of animal fats. It is always present in the skin and is converted to vitamin D3 on exposure to sunlight. 

Vitamin B group includes a heterogeneous number of compounds, some of them electrochemically oxidizable, which have been analyzed in several foods by isocratic reversed-phase HPLC-ED after acid or alkaline digestion and subsequent enzymatic extraction. The coulometric mode using Coulochem cells have been employed in these cases using an electrochemical guard cell at an oxidation potential closer to the final detection potential [96, 97], In all cases, the potential of the coulometric cell units were set to perform in the screening mode. Similar experimental scheme has been employed elsewhere for vitamin D3 and provitamin D3 analysis [98]. 

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