Vitamin isomerization

The synthesis of vitamin Dj from a sensitive dienone was another etu-ly success of phosphorus ylide synthesis (H.H. Inhoffen, 1958 A). This Wittig reaction could be carried out without any isomerization of the diene. An excess of the ylide was needed presumably because the alkoxides formed from the hydroxy group in the educt removed some of the ylide. 

Isomerization of double bonds in vitamin D analogs such as calciferol by oxidation and reduction has been carried out via the formation of the tt-allylpalladium complex 334 with PdCl2(PhCN)2 in 70% yield, followed by hydride reduction to afford 335[295],... 

The i j -configuration of the 6,7-double bond in pre-vitamin D is critical to its subsequent thermal rearrangement to the active vitamin. A photochemical isomerization of pre-vitamin D to yield the inactive trans-isoTnen occurs under conditions of synthesis, and is especially detrimental if there is a significant short wavelength component, eg, 254 nm, to the radiation continuum used to effect the synthesis. This side reaction reduces overall yield of the process and limits conversion yields to ca 60% (71). Photochemical reconversion of the inactive side product, tachysterol, to pre-vitamin D allows recovery of the product which would otherwise be lost, and improves economics of the overall process (70). 

Rearrangement of dehydrolinalool (4) using vanadate catalysts produces citral (5), an intermediate for Vitamin A synthesis as well as an important flavor and fragrance material (37). Isomerization of the dehydrolinalyl acetate (6) in the presence of copper salts in acetic acid followed by saponification of the acetate also gives citral (38,39). Further improvement in the catalyst system has greatly improved the yield to 85—90% (40,41). 

Hoffmaim-La Roche has produced -carotene since the 1950s and has rehed on core knowledge of vitamin A chemistry for the synthesis of this target. In this approach, a five-carbon homologation of vitamin A aldehyde (19) is accompHshed by successive acetalizations and enol ether condensations to prepare the aldehyde (46). Metal acetyUde coupling with two molecules of aldehyde (46) completes constmction of the C q carbon framework. Selective reduction of the internal triple bond of (47) is followed by dehydration and thermal isomerization to yield -carotene (21) (Fig. 10). 

In the BASF synthesis, a Wittig reaction between two moles of phosphonium salt (vitamin A intermediate (24)) and C q dialdehyde (48) is the important synthetic step (9,28,29). Thermal isomerization affords all /ra/ j -P-carotene (Fig. 11). In an alternative preparation by Roche, vitamin A process streams can be used and in this scheme, retinol is carefully oxidized to retinal, and a second portion is converted to the C2Q phosphonium salt (49). These two halves are united using standard Wittig chemistry (8) (Fig. 12). 

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. 

Fig. 3. Photochemical and thermal isomerization products of vitamin D manufacture (49). The quantum yields of the reactions ate hsted beside the arrows...

TorteUi-JaffH reaction acetic acid + 2 wt% Br2 in CHCl green sterols with ditertiary double bonds vitamin D and compounds that give similar bonds upon isomerization or... 

Vkiyl aHenes (44) are rearranged with heat or metal catalysis and photosensitized isomerization to produce the vitamin D triene (156—160). 

Industrially, vitamin is prepared from the chromic acid oxidation of 2-methylnaphthalene (56). Although the yields are low, the process is economical owing to the low cost and availabiUty of the starting material and the oxidizing agent. However, the process is compHcated by the formation of isomeric 6-meth5l-l,4-naphthoquinone. As a result, efforts have been directed to develop process technology to faciUtate the separation of the isomeric naphthoquinone and to improve selectivity of the oxidation. 

PApo-8 -carotenal. The specifications of this colorant. (38) were discussed earlier. P-Apo-8 -carotenal has provitamin activity with 1 g of the colorant equal to 1,200,000 lU of vitamin A. Like all crystalline carotenoids, it slowly decomposes ia air through oxidatioa of its coajugated double boads and thus must be stored ia sealed coataiaers uader an atmosphere of iaert gas, preferably under refrigeration. Also like other carotenoids P-apo-8 -carotenal readily isomerizes to a mixture of its cis and trans stereoisomers when its solutions are heated to about 60°C or exposed to ultraviolet... 

Carotenoids have two general characteristics of importance to the food iadustry they are not pH sensitive ia the normal 2—7 range found ia foods, and they are not affected by vitamin C, making them especially important for beverages. They are more expensive than synthetic food dyes and have a limited color range. In their natural environment they are quite stable, but they become more labile when heated or when they are ia solution. Under those conditions, there is a tendency for the trans-double bonds to isomerize to the cis-stmcture with a subsequent loss of color iatensity. The results of controlled tolerance and toxicity tests, usiag pure carotenoids, iadicate that they are perfecdy safe as food colors (132). 

Conjugation is crucial not only for the colors we see in organic molecules but also for the light-sensitive molecules on which our visual system is based. The key substance for vision is dietary /3-carotene, which is converted to vitamin A by enzymes in the liver, oxidized to an aldehyde called 11-frans-retinal, and then isomerized by a change in geometry of the C11-C12 double bond to produce 11-cis-retinal. 

Vitamin D3 (VD3) and retinoids synergistically inhibit the growth and progression of squamous cell carcinomas and actinic keratoses in chronically sun exposed skin. One reason for this synergism may be the direct influence of VD3 on the isomerization and the metabolism of RA. Here, VD3 inhibits the isomerization of 13-cis-RA to the more receptor active all-trans and 9-cis-isomers. Moreover, the VD3 derivative secocholestra-trien-l,3,24-triol (tacalcitol), used for the treatment of severe keratinizing disorders inhibits 4-hydroxylation of all-ri ans-RA. 

The other commonly quoted industrial photochemical process is the production of vitamin D3 involving a photochemical electrocyclic ring opening followed by a thermal 1,7-hydride shift (Scheme 7.2). This is a further example of a successful low quantum yield process in this case there is no viable thermal alternative. Vitamin A acetate has also been produced commercially using a photochemical isomerization process to convert a mixed tetra-alkene precursor to the all-trans form. 

Myo-inositol is one of the most biologically active forms of inositol. It exists in several isomeric forms, the most common being the constituent of phospholipids in biological cell membranes. It also occurs as free inositol and as inositol hexaphosphate (IP6) also known as phytate which is a major source from food. Rice bran is one of the richest sources of IP6 as well as free inositol. Inositol is considered to belong to the B-complex vitamins. It is released in the gastrointestinal tract of humans and animals by the dephosphorylation of IP6 (phytate) by the intestinal enzyme phytase. Phytase also releases intermediate products as inositol triphosphate and inositol pentaphosphate. Inositol triphosphate in cellular membrane functions as an important intra- and intercellular messenger, that merits its value as a nutritional therapy for cancer. 

Bleaching is reversed in the dark and the red-purple color of rhodopsin returns. This is thought to occur by the reduction of all-Pms-retinal to vitamin Ai (retinal), which diffuses from the rod into the pigment epithelium, where it is converted enzymatically to the 1 l-c isomer of vitamin At. The enzymatic isomerization is followed by diffusion back into the rod, oxidation to 11 -rfr-retinal, and combination with opsin to form rhodopsin. This process is shown schematically in Figure 12.5.[Pg.289]

Zechmeister, L. Cis-Trans isomeric carotenoids, vitamins A and arylpolyenes. Wien Springer 1962... 

In the stomach, carotenoids are exposed to acid environments. This can lead to carotenoid isomerization, which can change carotenoid antioxidant properties, solubility, and absorption. In humans, (3-carotene absorption is reduced when the pH of the gastric fluids is below 4.5 (Tang and others 1995). Vitamin E consumption seems to reduce carotenoid absorption in animals, presumably because vitamin E and carotenoids compete for absorption (Furr and Clark 1997). Dietary sterols, such as those in sterol-supplemented functional foods, are also known to decrease carotenoid absorption. 

L. Zechmeister, Cis-Trans Isomeric Carotenoids, Vitamins A, and Arylpolyenes, Academic Press, New York, 1962. 

Takaya and co-workers46 found that BINAP-based Ru(II) dicarboxylate complexes 31 can serve as efficient catalyst precursors for enantioselective hydrogenation of geraniol (2E)-32 and nerol (2Z)-32. (R)- or (iS )-citroncllal 33 is obtained in nearly quantitative yield with 96-99% ee. The nonallylic double bonds in geraniol and nerol were intact. Neither double bond migration nor (fi)-/(Z)-isomerization occurred during the catalytic process. Furthermore, the S/C ratio was extremely high, and the catalyst could easily be recovered (Scheme 6-18). This process can be applied to the asymmetric synthesis of a key intermediate for vitamin E. 

The next five transition metals iron, cobalt, nickel, copper and zinc are of undisputed importance in the living world, as we know it. The multiple roles that iron can play will be presented in more detail later in Chapter 13, but we can already point out that, with very few exceptions, iron is essential for almost all living organisms, most probably because of its role in forming the amino acid radicals required for the conversion of ribonucleotides to deoxyribonucleotides in the Fe-dependent ribonucleotide reductases. In those organisms, such as Lactobacilli6, which do not have access to iron, their ribonucleotide reductases use a cobalt-based cofactor, related to vitamin B12. Cobalt is also used in a number of other enzymes, some of which catalyse complex isomerization reactions. Like cobalt, nickel appears to be much more extensively utilized by anaerobic bacteria, in reactions involving chemicals such as CH4, CO and H2, the metabolism of which was important... 

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