Vitamin partial synthesis

The stereocontroUed syntheses of steroid side chains for ecdysone, cmstecdysone, brassinoHde, withanoHde, and vitamin D have been reviewed (185). Also, other manuscripts, including reviews on the partial synthesis of steroids (186), steroid dmgs (187—189), biologically active steroids (190), heterocychc steroids (191), vitamin D (192), novel oxidations of steroids (193), and template-directed functionali2ation of steroids (194), have been pubhshed. 

The isophytol side chain can be synthesized from pseudoionone (Fig. 5) using chemistry similar to that used in the vitamin A synthesis (9). Hydrogenation of pseudoionone (20) yields hexahydropseudoionone (21) which can be reacted with a metal acetyUde to give the acetylenic alcohol (22). Rearrangement of the adduct of (22) with isopropenyknethyl ether yields, initially, the aHenic ketone (23) which is further transformed to the C g-ketone (24). After reduction of (24), the saturated ketone (25) is treated with a second mole of metal acetyUde. The acetylenic alcohol (26) formed is then partially hydrogenated to give isophytol (14). 

R)-pantothenic acid is an obvious candidate to be produced via fermentation, because all microorganisms synthesize the vitamin to meet their own requirements. Takeda Chemical Industries has developed a microbial partial synthesis of (R)-pantothenate in an E. coli mutant with enhanced expression of the panB, panC and panD genes [115]. High levels of (R)-pantothenate, 60 gL-1 [116], which corresponds with 30 g L-1 d-1, were obtained when 3-aminopropionate was fed to the culture. Presumably, fermentation of (R)-pantothenate with sup-pletion of 3-aminopropionate is used by Degussa in the production of Biopan . 

Ananthanarayan, T.P., Magnus, P, and Norman, A.W., Reductive cleavage of the 9,10-bond in 11-oxygenated steroids. A new method for the partial synthesis of the vitamin D skeleton, J. Chem. Soc., Chem. Commun., 1096, 1983. 

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. 

An important raw material for the partial synthesis of steroid hormones (and Vitamin D) is cholesterol, which (prior to the BSE crisis) was isolated from the spinal cord of cattle. Another important source is the fat in sheep s wool (lanolin), which contains around 15 % of cholesterol. Among the plant sterols, stigmasterol is of great economic significance as the starting material for the partial synthesis of steroids. It is contained from 12 to 25 % in the non-hydrolysable... 

Harmeyer, J., and H. F. DeLuca Calcium Binding Protein and Calcium Absorption after Vitamin D Administration. Arch. Biochem. Biophys. 133, 247 (1969). Harrison, I. T., and B. Lythgoe Calciferol and its Relatives. Part III. Partial Synthesis of Calciferol and of Epicalciferol. J. Chem. Soc. (London) 1958, 837. Harrison, R. G., B. Lythgoe, and P. W. Wright Calciferol and its Relatives. Part XVIII. Total Synthesis of la-Hydroxyvitamin D3. J. Chem. Soc. Perkin I 1974, 2654. 

Lenhert and Hodgkin (15) revealed with X-ray diffraction techniques that 5 -deoxyadenosylcobalamin (Bi2-coenzyme) contained a cobalt-carbon o-bond (Fig. 3). The discovery of this stable Co—C-tr-bond interested coordination chemists, and the search for methods of synthesizing coen-zyme-Bi2 together with analogous alkyl-cobalt corrinoids from Vitamin B12 was started. In short order the partial chemical synthesis of 5 -de-oxyadenosylcobalamin was worked out in Smith s laboratory (22), and the chemical synthesis of methylcobalamin provided a second B 12-coenzyme which was found to be active in methyl-transfer enzymes (23). A general reaction for the synthesis of alkylcorrinoids is shown in Fig. 4. 

Lead was found to decrease tissue levels of vitamin C in a study in rats (Vij et al. 1998). Since vitamin C is required for the synthesis of heme, the authors suggested that some hematological effects of lead (e.g., inhibition of ALAD) may be due at least partially to a lead-induced decrease in bioavailability or increased demand of vitamin C. Supplementation with vitamin C almost completely restored ALAD activity in blood and liver. 

Industrial synthesis of vitamin A (Hoffman-La-Roche) goes through partial hydrogenation of an enyne (equation 161)277. A number of syntheses of pheromones, where the reduction of an enyne to a diene is the key step, have been devised. A few selected examples are given in Table 29278. During the total synthesis of endiandric acids, Nico-laou employed hydrogenation of a polyenyne intermediate with a Lindlar catalyst to generate an intermediate which underwent symmetry-allowed cyclizations to result in the natural product (equation 162)279. 

A partial list of physiological functions til at have been determined to be affected by vitamin C deficiencies includes (1) absorption of iron (2) cold tolerance, maintenance of adrenal cortex (3) antioxidant (4) metabolism of tryptophan, phenylalanine, and tyrosine (5) body growth (6) wound healing (7) synthesis of polysaccharides and collagen (8) formation of cartilage, dentine, bone, and teeth and (9) maintenance of capillaries. 

Bioavailability of Niacin. Factors which cause a decrease in macm availability include (1) Cooking losses (2) bound form in corn (maize), greens, and seeds is only partially available (3) presence of oral antibiotics (4) diseases which may cause decreased absorption (5) decrease in tiyptophan conveision as in a vitamin B deficiency. Fac.tois that increase availability include (1) alkali treatment of cereals (2) storage in bver and possibly in muscle and kidney tissue and (3) increased intestinal synthesis. 

Stobbe s wish has been only partially fulfilled in the century which has elapsed in the meantime. Whilst many photochemical reactions have been discovered, certainly many more wait to be uncovered, and it still holds true that more photochemistry carried out by synthetic chemists would contribute to the growth of photochemistry as a whole. This Handbook represents a modest attempt to contribute towards this aim and to foster the synthetic use of photochemistry. The presentation is referred to the small-scale laboratory synthesis of fine chemicals. In this aspect, the photochemical literature does not differ from the large majority of published synthetic work, most of which is carried out on the 100 mg scale for exploratory studies. However, there is no reason to think that a photochemical reaction is unfit for scaling up. As will shown below, an increase up to the 100 g scale can be obtained in the laboratory by simple arrangements. Furthermore, while the presently running industrial applications are limited in number, they are nonetheless rather important [3]. Some of these are well established, an example being the synthesis of vitamin D3 which has been produced at the several tons level each year for several decades, and for which dedicated plants continue to be built. This indeed demonstrates that photochemical syntheses are commercially viable. 

The isolation of the biologically active metabolite of vitamin D3 in a pure state, and the determination of its structure as 25-hydroxycholecalciferol (401) has been rapidly followed by its synthesis via irradiation of 25-hydroxycholesta-5,7-dien-3j -ol by three independent groups. The first synthesis of pre-calciferola (405) has been achieved by reaction of the lithium derivative of the chloro-ketone (402) with the en-yne (403) to give (404) which was treated with bis(ethylenediamine)chromium(ii) and then partially reduced catalytically. The thermal isomerisation of (405) (as 3,5-dinitrobenzoate) to vitamin D3 represents the first non-photochemical synthesis. 

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