Vitamin isomers

Epimerization of the lot-hydroxyl group of lot-OH-Ds has been accomplished in a three-step sequence Mn02 allyUc oxidation to the 1-keto previtamin analog, reduction to a mixture of la- and 1 hydroxy previtamins, and thermal isomerization to the vitamin isomers scheme (30)]. Vitamin D 1,3-diol stereoisomers... 

Commercially, the irradiation of the 5,7-diene provitamin to make vitamin D must be performed under conditions that optimize the production of the previtamin while avoiding the development of the unwated isomers. The optimization is achieved by controlling the extent of irradiation, as well as the wavelength of the light source. The best frequency for the irradiation to form previtamin is 295 nm (64—66). The unwanted conversion of previtamin to tachysterol is favored when 254 nm light is used. Sensitized irradiation, eg, with fluorenone, has been used to favor the reverse, triplet-state conversion of tachysterol to previtamin D (73,74). 

Preferably, high pressure Hquid chromatography (hplc) is used to separate the active pre- and cis-isomers of vitamin D from other isomers and allows their analysis by comparison with the chromatograph of a sample of pure reference i j -vitainin D, which is equiUbrated to a mixture of pre- and cis-isomers (82,84,85). This method is more sensitive and provides information on isomer distribution as well as the active pre- and cis-isomer content of a vitamin D sample. It is appHcable to most forms of vitamin D, including the more dilute formulations, ie, multivitamin preparations containing at least 1 lU/g (AOAC Methods 979.24 980.26 981.17 982.29 985.27) (82). The practical problem of isolation of the vitamin material from interfering and extraneous components is the limiting factor in the assay of low level formulations. 

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. 

As described ia the USP, phytoaadioae is a mixture of the cis- and trans-isomers of vitamin IQ. This mixture should not contain mote than 103% and not less than 97.0% of total vitamin K content. The amount of the cis-isomer is also specified and is not to exceed 21%. In addition to the pure substance, the USP also describes methods for the analysis of parental as well as tableted forms of the vitamin (21). 

Dye-Sensitized Photoisomerization. One technological appHcation of photoisomerization is in the synthesis of vitamin A. In a mixture of vitamin A acetate (all-trans stmcture) and the 11-cis isomer (23), sensitized photoisomerization of the 11-cis to the all-trans molecule occurs using zinc tetraphenylporphyrin, chlorophyU, hematoporphyrin, rose bengal, or erythrosin as sensitizers (73). Another photoisomerization is reported to be responsible for dye laser mode-locking (74). In this example, one metastable isomer of an oxadicarbocyanine dye was formed during flashlamp excitation, and it was the isomer that exhibited mode-locking characteristics. 

The alkyne hydrogenation reaction has been explored extensively by the Hoffmann-La Roche pharmaceutical company, where it is used in the commercial synthesis of vitamin A. The cis isomer of vitamin A produced on hydrogenation is converted to the trans isomer by heating. 

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. 

Diugs with metabolic interactions that can enhance the half-life of active compounds. An example of this regimen is the interaction between azole- and vitamin D-deiivatives that inhibit the metabolism of retinoids in skin cells leading to increased intracellular amounts of active RA-isomers. Further study and the identification of novel interactions of this type ofdtug interaction is of great clinical interest since they may decrease the dose of retinoids required for efficacy thereby also reducing the risk of side effects of the retinoids. 

An isomer (molecule with the same number and type of atoms but in a different formation) of ascorbic acid called erythorbic acid is often used as a less expensive antioxidant than ascorbic acid. It has little or no effect as a vitamin, but it has the same antioxidant properties. 

Tocopherols and tocotrienols belong to the vitamin E family of compounds, which are potent antioxidants. The four isomers of tocotrienols (a-T3, P-T3, y-T3, 8-T3) are structurally related to their corresponding homologues of tocopherols (a-T, p-T, y-T, 8-T), but differ in their side-chain in that T3... 

In order to exhibit provitamin A activity, the carotenoid molecule must have at least one unsubstituted p-ionone ring and the correct number and position of methyl groups in the polyene chain. Compared to aU-trans P-carotene (100% provitamin A activity), a-carotene, P-cryptoxanthin, and y-carotene show 30 to 50% activity and cis isomers of P-carotene less than 10%. Vitamin A equivalence values of carotenoids from foods have been recently revised to higher ratio numbers (see Table 3.2.2) due to poorer bioavailability of provitamin A carotenoids from foods than previously thought when assessed with more recent and appropriate methods. 

Trigueiro, I.N.S. and Penteado, M.V.C., Stereochemical isomers composition and vitamin A value of Brazilian pahn oils, Arch. Latinoamer. Nutr., 46, 334, 1996. 

Guyan et al. 1990) have used several markers of lipid peroxidation (9-cis-, 11-tmns-isomer of linoleic acid, conjugated dienes and ultraviolet fluorescent products) to demonstrate significant increases in the duodenal aspirate after secretin stimulation in patients with acute and clinic pancreatitis. They interpreted this as indicating induction of hepatic and pancreatic drug-metabolizing enzymes in the face of a shortfidl of antioxidant defences, more marked in chronic pancreatitis. Subsequent studies in patients with chronic pancreatitis have confirmed decreased serum concentrations of selenium, -carotene and vitamin E compared with healthy controls (Uden et al., 1992). Basso aol. (1990) have measured increases in lipid peroxides in the sera of patients with chronic... 

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]

High, E. G. and H. G. Day (1951). Effects of different amounts of lutein, squalene, phytol and related substances on the utilization of carotene and vitamin A for storage and growth in the rat. J. Nutr. 43 245-260. Johnson, E. J. et al. (1997). Beta-carotene isomers in human serum, breast milk and buccal mucosa cells after continuous oral doses of -trans and 9-cis beta-carotene. J. Nutr. 127(10) 1993-1999. 

Carotene (all-trans), (3-cryptoxanthin (all-trans and -cis), zeaxanthin (all-trans), luteoxanthin isomers, violaxanthin (all-trans and -cis), and neoxanthin (all-trans and -cis) were identified in several mango cultivars (Mercadante and others 1997 Ornelas-Paz and others 2007, 2008). Mango retinol was found to be highly bioavail-able by estimating vitamin A and carotene reserves in the liver and plasma of rats. Information on the tocopherol content in mango is very scarce, but it seems to be low (Burns and others 2003 Ornelas-Paz and others 2007). 

Suitably positioned vinyl halide can undergo Heck-type intramolecular coupling to generate dienes (equations 124 and 125)216,217. When one of the reacting partners in the Heck reaction is a diene, trienes are obtained (equation 126)218. Heck coupling of ally lie alcohols and alkenyl iodides has been employed for the synthesis of vitamin A and related compounds (equation 127)219,220. A similar double Heck reaction on a Cio-diiodide with a Cis-allylic alcohol leads to -carotene as a mixture of isomers (equation 128)209e. 

Vitamin B12 catalyzed also the dechlorination of tetrachloroethene (PCE) to tri-chloroethene (TCE) and 1,2-dichloroethene (DCE) in the presence of dithiothreitol or Ti(III) citrate [137-141], but zero-valent metals have also been used as bulk electron donors [142, 143]. With vitamin B12, carbon mass recoveries were 81-84% for PCE reduction and 89% for TCE reduction cis-l,2-DCE, ethene, and ethyne were the main products [138, 139]. Using Ni(II) humic acid complexes, TCE reduction was more rapid, leading to ethane and ethene as the primary products [144, 145]. Angst, Schwarzenbach and colleagues [140, 141] have shown that the corrinoid-catalyzed dechlorinations of the DCE isomers and vinyl chloride (VC) to ethene and ethyne were pH-dependent, and showed the reactivity order 1,1-DCE>VC> trans-DCE>cis-DCE. Similar results have been obtained by Lesage and colleagues [146]. Dror and Schlautmann [147, 148] have demonstrated the importance of specific core metals and their solubility for the reactivity of a porphyrin complex. 

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