Retinaldehyde derivatives

A procedure for the preparation of 1-bromoacetylenes and conjugated enynes77 has been used to make the retinaldehyde derivative (126). Retro-aldol reaction of the retinylidenedimedone (127) with MeNHa gave all-Pms-retinaldehyde in 90% yield.78 Oxidation of (127) gave the 5,6- and 5,8-epoxides (128) and (130).79 The 4-acetoxy-, 4-hydroxy-, and 4-keto-derivatives (131) (X = H,OH, H,OAc, and O respectively) and the seco-compound (133) were also prepared. Compounds (128), (130 X = O), and (131) underwent retro-aldol reaction to give the aldehydes... 

Retinaldehyde (2) was brominated with A -bromosuccinimide (NBS) to give an intermediate that was not isolated but was converted by nucleophilic substitution reactions to a large number of retinaldehyde derivatives of the (321) type, pos sessing functional groups in position 4 (Surmatis, 1967 Surmatis, et aL, 1970 Serebryanyi et aL, 1981). 

The diastereomeric retinaldehyde derivatives (394), (395), (396), and (397) were synthesized from the ketone (390) by the following procedure (Nakanishi et aL, 1976) The allenic ketone (390) was reacted with the C2 phosphonate (167) to give the mixture of ester isomers (391), which was reduced with di-isobutylaluminum hydride (DIBAL) and then oxidized with manganese dioxide. The 9 -cis aldehyde (392) was separated by chromatography and was reacted with the C5 phosphonate (166) to give a mixture of 9Z, 2>E and 9Z 13Z isomers of the ester (393). Treatment of the 9-cis, 13-trans ester with DIBAL and manganese... 

For rhodopsin studies, retinaldehyde derivatives that possess an 11-cis configuration and cannot undergo isomerization to the all-trans form were synthesized. These compounds were obtained by incorporating the double bond in a... 

The stmcture of vitamin A [11103-57-4] and some of the important derivatives are shown in Figure 1. The parent stmcture is aH-Zra/ j -retinol [68-26-8] and its lUPAC name is (all-E)-3,7-dimethyl-9-(2,6,6-trimethyl-l-cyclohexen-l-yl)-2,4,6,8-nonatetraen-l-ol (1). The numbering system for vitamin A derivatives parallels the system used for the carotenoids. In older Hterature, vitamin A compounds are named as derivatives of trimethyl cyclohexene and the side chain is named as a substituent. For retinoic acid derivatives, the carboxyl group is denoted as C-1 and the trimethyl cyclohexane ring as a substituent on C-9. The stmctures of vitamin A and -carotene were elucidated by Karrer in 1930 and several derivatives of the vitamin were prepared by this group (5,6). In 1935, Wald isolated a substance found in the visual pigments of the eye and was able to show that this material was identical with Karrer s retinaldehyde [116-31-4] (5) (7). 

Vitamin A (retinol), present in carnivorous diets, and the provitamin (P-carotene), found in plants, form retinaldehyde, utilized in vision, and retinoic acid, which acts in the control of gene expression. Vitamin D is a steroid prohormone yielding the active hormone derivative calcitriol, which regulates calcium and phosphate metaboUsm. Vitamin D deficiency leads to rickets and osteomalacia. 

Figure 23-5 Resonance Raman spectra. (A) Of the retinaldehyde-containing bacteriorhodopsin bR568 (see Fig. 23-45) and its 12,14-2H and 14-13C isotopic derivatives. (B) Of bRS68 labeled with the dominant internal coordinates that contribute to the normal modes. From Lugtenburg et al 7...

Saari has made the bold statement that Three derivatives of 11-cis-retinaldehyde serve as the chromophores of all known visual pigments. They are complexed with a protein component (an opsin), and the resulting protein-retinoid interactions determine the spectral sensitivity of the visual pigment. 85 No reference is given for this statement nor is any explanation of how these complexes exhibit an absorption spectrum in the visual region. However, except for the substitution of all-trans for 11 -cis in the above quotation and a slight modification to the retinoid involved, this work agrees completely with the statement and provides an explanation for how it is applied. 

The main physiologically active forms of vitamin A are retinaldehyde and retinoic acid, both of which are derived from retinol. Retinaldehyde functions in the visual system as the prosthetic group of the opsins, which act as the signal transducers between reception of light in the retina and initiation of the nervous impulse. 

A-2 Vitamin A consists of three biologically active molecules, retinol, retinal (retinaldehyde) and retinoic acid. Each of these compounds are derived from a group of molecules know as carotenoids also referred to as the provitamin A. Beta-carotene, which consists of two molecules of retinal linked at their aldehyde ends. 

I- cis- and 7,13-di-ciy-isomers of vitamin A [retinol (91)] have been prepared via the 1-cis photoisomerization product of the sulphone (94).62 Several isotopically labelled species of retinaldehyde and derivatives have been synthesized, including... 

Many retinaldehyde, retinol, and retinoic acid derivatives and analogues have been synthesized. The (3i )-3-hydroxy-derivatives (98), (99), and (100) were prepared from the optically active C15 Wittig salt (31).68 9-Bromoretinaldehyde (101 trans and 9-cis), 13-bromoretinaIdehyde (102 trans and ll-cis), phenyl-retinaldehyde (103 trans and 9-cis), and p-dimethylami nophenyl retinaldehyde (104 trans) have been prepared and used to make bacteriorhodopsin analogues.69 5,6-Dihydroretinaldehyde (105) and its desmethyl analogue (106) also formed... 

A study of solvent effects on the photoisomerization of retinaldehyde and the Ci5 aldehyde (140) and Q8 ketone (141) has been reported.85 The kinetics of formation and decay of radical anions of all-f/vmy-retinaldehyde and derivatives... 

Finally, in the past few years a large number of derivatives of natural retinaldehyde have been synthesized for use in the study of mechanistic details of the formation and function of rhodopsin (Vision Symposium, 1979 Sen et al., 1982 Liu and Asato, 1982) and bacteriorhodopsin (Ebrey and Yoshizawa, 1981). The efforts in the field of synthesis have been accompanied by the rapid development of analytical methods, especially NMR spectroscopy and high-performance liquid chromatography (HPLC), which permit rapid and reliable structure assignment. 

In 1960, lUPAC drew up a number of recommendations and rules for the nomenclature of vitamin A derivatives, and only recently lUPAC-IUB published new rules on the nomenclature of retinoids (lUPAC-lUB, 1982), which we follow in this book in naming retinoids. The basic structures are called retinol (1), retinaldehyde (2), and retinoic acid (3), and these names always refer to the... 

The absorption spectra of 3,4-didehydroretinaldehydes are very similar to those of retinaldehydes (von Planta et al, 1962 Morton, 1972), whereas the spectra of retinaldehyde Schiff bases are very similar to those of the aldehydes from which these compounds are derived (Schaffer et al, 1974 Sandorfy,... 

A number of interesting observations may be derived from the electronic spectra of novel retinoid structures. Table III shows the absorption data of isomeric retinaldehydes. 

It was possible to obtain dihydroretinaldehydes from corresponding di-hydroretinoic acid derivatives (Blatz et al., 1968 Gawinowicz et al, 1977 Amaboldi et aL, 1979). These retinaldehydes have been employed in vision research (Honig et al, 1979 Nakanishi et aL, 1979). 

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