Vitamin Geometric isomers

Conditions have been optimized for catalytic hydrogenation of the acetylene group of the vitamin A synthesis intermediate (110). Several chemical reactions of geometrical isomers of the product (111) and its acetate and of (110) have been described. " ... 

However, the effects of chelation allow the formation of one geometric isomer. One example, where the exclusive formation of the lithiated Z-isomer is due to chelation of lithium with an acetal oxygen is described in the asymmetric synthesis of vitamin E62. 

Adsorption chromatography is a powerful means of separating cis and trans isomers of unsaturated compounds, the separation mechanism being attributed to a steric fitting of solute molecules with the discrete adsorption sites. This is illustrated in the isocratic separation of six geometric isomers of vitamin A obtained by photolysis of all-fran.v-retinol (109). 

B Stancher, F Zonta. High performance liquid chromatographic determination of carotene and vitamin A and its geometric isomers in foods. Applications to cheese analysis. J Chromat 238.217-225, 1982. 

A number of geometric isomers of retinol exist because of the possible cis-trans configurations around the double bonds in the side chain. Fish liver oils contain mixtures of the stereoisomers synthetic retinol is the all-trans isomer. Interconversion between isomers readily takes place in the body. In the visual cycle, the reaction between retinal (vitamin A aldehyde) and opsin to form rhodopsin only occurs with the 11 -cis isomer. 

Naphtomycin A (54) was isolated from S. collinus and its structure was clarified by means of spectral methods. Naphtomycin A is a strong vitamin K antagonist. In addition to naphtomycins A and H (55), a geometric isomer of naphtomycin B (56), was produced by a streptomycete isolated from the Indian soil [39]. 

On silica gel thin-layer chromatography (TLC) plates eluted with a mixture of cyclohexane-ethanol (97 3, by volume), vitamin Aj alcohol and re/ro-vita-min Ai alcohol (Rp values 0.10 and 0.09, respectively) are separated from the pair vitamin Aj acetate/re/ro-vi-tamin Aj acetate (Rp values 0.48 and 0.45, respectively) and vitamin Aj palmitate (Rp value 0.78) and anhy-drovitamin Aj (Rp value 0.87) [5]. Geometric isomers of retinol are separated on silica gel plates using... 

Cis-trans isomerisation may be a cause of loss of potency of a dmg if the two geometric isomers have different therapeutic activities. Vitamin A (all-frans-retinol) is enzymatically... 

Carotenoids and Related Compounds.— The synthesis of the last two unsynthesized geometrical isomers of vitamin A (7-cis, 9-cis, ll-cis, and all cis) has been accomplished. 2,2 -Dinorcanthaxanthin (113) and canthaxanthin (114) have been synthesized in high yield by Wittig reaction of the dialdehyde (112) with the ylides (110) and (111), respectively. 

Liu, R. S. H., A. E. Asato, and M. Denny New geometric isomers of vitamin A and carotenoids. 5,7-cw-3-dehydroretinal and 7-d.v-3-dehydro-Ci8-ketone from direct irradiation of the trans isomers in polar solvents. J. Amer. Chem. Soc. 99, 895 (1977). 

In contrast to what happens when only a single covalent bond connects two carbons, a double bond restricts the rotation around the carbon-to-carbon bond. This gives rise to geometric isomers. Consider a compound much more simple than the polyene chain of vitamin A, namely, dichlorethylene. The two carbons, the two hydrogens, and the two chlorides are located in the same plane, so there are two possible relationships for the two chlorides they can both be in the upper part of the plane cis form) or one chloride can be above and the other below (the median plane, or trans, form). 

Vitamin A has four such double bonds therefore, 32 different geometrical isomers are possible. Only those four isomers that exist in nature will be considered here. The trans form (see Fig. 4-33) is the most stable form, so most natural compounds contain mainly trans vitamin A. However, it is possible to con-... 

Groenendijk et al. (13) were able to separate several geometric isomers of vitamin A compounds using silica gel plates. In their hands, activation of the plates by heating to 120 C rarely resulted in enhanced resolution. Mixtures of a low boiling alkane (hexane, petroleum ether, or cyclohexane) and a variable amount of a more polar solvent (8% diethyl ether, 50% diethyl ether or 20% ethyl acetate) were used. In these systems, retinol isomers move slower than the retinals, whereas the retinyl ester isomers move rather close to the solvent front. Moreover, for the retinyl ester isomers no separation is obtained. Also, it seems to be very difFicult to separate the different isomers of retinal. Modification to retinal oximes, however, facilitates the separation and identification since each isomer results in... 

Table 1 Representative R/ values of Geometric Isomers of Vitamin A Compounds...

In the vitamin Kj forms and their isoprenologs geometric isomers are possible, owing to the double bonds present in the side chain. The all-frans, the 6, 7 -mono-cts, and the 18, 19 -mono- s forms of vitamin Kjuo) were... 

Biological Activity of the Geometric Isomers op Vitamin Kj WITH A Cjo AND Cao Side Chain... 

Fio. 16. Activity of the geometric isomers of vitamin Ki(io>. White columns biological activity in the chick. Black columns reactivation of the cytochrome c reductase. 

Biesalski and Weiser separated a -trans from l3-cis, W-cis, and 9-cis isomers of retinyl esters (retinyl palmitate, stearate, oleate, palmitoleate, and linole-ate) by isocratic adsorption HPLC (126). Bridges et al. used step gradients to separate geometric isomers of retinyl esters, retinal, retinal oximes, and retinal (both vitamin Ai and vitamin A2 forms), also by adsorption ( normal-phase ) HPLC (139,140). 

Milk. Simultaneous analysis of retinol and carotenoids present in human milk was carried out on a YMC RP 5-p.m ODS column (0.46 X 25 cm) by isocratic elution with tetrahydrofuran/methanol (90 10) (216). Thirty-four carotenoids, including 13 geometric isomers and eight metabolites, along with vitamins A and E in milk of lactating mothers, were separated by a combination of normal and RP-HPLC (217). 

Food sample pretreatment may consist of either (a) saponification to quantify the free forms (retinol or xanthophylls may occur free or ester-ified in foods) [95,96] or (b) direct extraction to determine the unaltered A vitamers [84,88]. Alkaline hydrolysis is also an expedient to simplify the vitamin A analysis, since retinol is the only form to be quantified nevertheless, due to its sensitivity to light and oxygen, it is important to prevent photo-oxidation by inclusion of a antioxidant (ascorbic acid, hydroquinone, or pyrogallol). A drawback of hot saponification is the generation of artifacts, such as geometric isomers of retinol and carotenoids [97]. 

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