Retinol derivatives

Retinol Derivatives. Aryl sulphones have been used in two new syntheses in the vitamin A series. Reaction of /8-cyclocitryl phenyl sulphone (102) with the bromo-compound (103) gives the intermediate sulphone (104), which on base-catalysed elimination affords methyl retinoate (98). Alternatively retinol (99) has been prepared in high yield by condensation of the C15 bromide (105) with the C5 hydroxy-sulphone (106), followed by elimination of sulphinic acid. The syntheses 

Reagents i, (CH20H)2 ii, N2CH2C02Et iii, L1AIH4 iv, BF3-ACOH-H3PO4 v, THP vi, Wittig reaction vii, PPh3-HCI-MeOH viii, C14 dial 

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.  

Some conversion into the anhydrovitamin (112) occurs during silica gel t.l.c. of retinyl palmitate in non-polar solvents. Some new colour reactions of vitamin A are reported to be better than the Carr-Price reaction. The kinetics and mechanism of acid-catalysed isomerization of retinyl acetate into the trans-retro-derivative (113) have been studied. Oppenauer oxidation of kitol (39) results in specific cyclopentanol-cyclopentanone oxidation.  

---

Biesalski, FI. K. (1996). Effects of intratracheal application of vitamin A on concentrations of retinol derivates in plasma, lungs and selected tissue of rats. Int. ]. Vitam. Nutr. Res. 66, 106-112. 

Transport to the liver Retinol esters present in the diet are hydrolyzed in the intestinal mucosa, releasing retinol and free fatty acids (Figure 28.19). Retinol derived from esters and from the cleavage and reduction of carotenes is reesterified to long-chain fatty acids in the intestinal mucosa and secreted as a component of chylomicrons into the lymphatic system (see Figure 28.19). Retinol esters contained in chylomicrons are taken up by, and stored in, the liver. 

From here on, our emphasis will not fall on retinol itself but on its derivatives. This is because although retinol derives from a well-known natural dye, carotene retinol and the retinenes are not dyes themselves. While they exhibit a minor absorption at 500 nm in the visual spectrum when in dilute solution, this absorption feature is not used in the visual system. Normally, it cannot be measured in-vivo because of the much greater absorption coefficients related to the molecules when in the liquid crystalline state. 

Retinol Derivatives. The sulphone method forms the basis of three new synthetic routes to vitamin A (retinol 95), involving condensation of the /3-ionylidene-ethyl (Cis) phenyl sulphone (96) with the epoxide (97) " or the chloride (98) or condensation of the /8-ionyl phenyl sulphone (99) with the allylic chloride (100). Conditions have been developed under which the elimination of the sulphone group from the reaction intermediate (101) occurs efficiently. In another stereospecific... 

In 1935 Hamano and Kawakami (1935) characterized retinol (1) as the P-naphthoate and anthraquinone P-carboxylate. Later Baxter and Robeson (1940) were able for the first time to obtain crystalline retinyl palmitate (113) and crystalline retinol (1) from liver oils. Crystalline retinyl acetate (9) and crystalline retinyl succinate were obtained at a later date (Baxter and Robeson, 1942). These very pure compounds made possible the accurate determination of a number of physical data. In 1946 Hanze et al. (1948) synthesized pure retinyl methyl ether (571) from crystalline retinol (1), and the total synthesis of this ether was reported at the same time by Milas et al. (1948). At this time also, syntheses of retinoids were carried out by Isler and associates and led to the first industrial synthesis of retinol derivatives (Isler et al., 1947 Isler, 1950 Heilbron and Weedon, 1958 Isler, 1979). 

The structures of the isomeric retinol derivatives (36), (37), and (38) were also established on the basis of nuclear Overhauser experiments (Chandraratna and... 

Among the retinol derivatives, only a weak p band, just evident at 77°K, was observed. (9Z)-Retinol (132) has perhaps the most intense p band, whereas (1 lZ)-retinol (376) scarcely absorbs in this region. However, (1 lZ)-retinol (376) exhibits a 7 band that is unusually intense for retinols (Morton, 1972). The spectra of 3,4-didehydroretinols exhibit an intense p band and no obvious 7 band. The relative order of intensities for the p band is 9Z > 13Z all-E (Morton, 1972). Additionally, two-photon spectroscopy has been employed successfully for the determination of excited states of retinoids (Birge, 1982 Birge etal.y 1982). 

It was also possible to introduce an acetoxy functional group into the cyclo-geranyl ring of the C20 phosphonium salt (325) using iV-bromosuccinimide in the presence of acetic acid the compound (326) was obtained (Surmatis et al., 1970). The chloride (328) was obtained by the usual method of synthesizing C20 phosphonium salts from the retinol derivative (327) and triphenylphosphine in methanol containing hydrochloric acid (Surmatis, 1967). 

In this manner, 10,14-retroretinol (383) was converted to the retinol derivatives (375), (384), and (376), which were isolated as pure isomers (Knudsen et aL, 1980). Once again, the zm-butyldimethylsilyl ether of (383) is just as suitable for this reaction as (383) itself. Compound (384) was oxidized with... 

It is very probable that (551) is formed by a sequence of tandem electrocycli-zations of the putative 9-c/5,ll-cw-retinol isomer. The retinol derivatives (38), (550), and (37) were oxidized with manganese(IV) oxide to the corresponding 12-s-dy-locked aldehydes. 

V-Retinylmorpholine (590) was prepared by nucleophilic substitution in an activated retinol derivative (Pisano and Firestone, 1981). The lithium alkoxide of (1) was reacted with p-toluenesulfonyl chloride at a low temperature to give the tosylate (589) that reacted in situ with morpholine to give iV-retinylmorpholine (590), which is not very stable. 

Fig. 9. Separation of a mixture of retinol derivatives (1 p-g each) by gas-liquid chromatography. 1% SE-30 on silanized 80 mesh Gas-Chrom P 35 cm packed glass column vaporizor, 230 column, 150 detector and outlet, 165 150 ml argon/min. The peak labeled retinal is retinaldehyde. (Reprinted with permission from Dunagin and Olson, 1964.)...

The third category of signaling lipids are those serving as activators of G-protein-coupled receptors, including lysoGPLs (lysoPA in particular), SIP, platelet-activating factor (PAF), endocannabinoids, eicosanoids, fatty acid-hydroxy fatty acids, and retinol derivatives. Increased mass levels of these lipids may lead to the activation of the corresponding G-protein-coupled receptor(s). 

---