Retinal isomerisation

The initial act in the process of vision involves the photochemical cis-trans isomerisation of the 11-cis C=C bond of the retinal chromophore... 

The absorption of light by CM-retinal converts it to the trans-form which induces a conformational change in opsin. One photon catalyses the isomerisation of one molecule of... 

For vision to continue, c/s-retinal must be regenerated. The /rans-retinal is reduced to /rans-retinol (i.e. the aldehyde is converted to alcohol) and is isomerised to c/s-retinal this is oxidised to c/s-retinol (see Figure 15.9(b)). Two different cells are involved the oxidation of retinal to retinol occurs in the photoreceptor cell. The retinol is then released and is taken up by the adjacent epithelial cell where it is isomerised to c/s-retinol and then reduced to... 

Figure 15.11 The biochemical reactions that result in the conversion of trans-retinal to ds-retinal, to continue the detection of light To continue the process, trans-retinal must be converted back to c/s-retinal. This is achieved in three reactions a dehydrogenase converts trans-retinal to trans-retinol an isomerase converts the trans-retinol to c/s-retinol and another dehydrogenase converts c/s-retinol to c/s-retinal. To ensure the process proceeds in a clockwise direction (i.e. the process does not reverse) the two dehydrogenases are separated. The trans-retinal dehydrogenase is present in the photoreceptor cell where it catalyses the conversion of trans-retinal to trans-retinol which is released into the interstitial space, from where it is taken up by an epithelial cell. Here it is isomerised to c/s-retinol and the same dehydrogenase catalyses its conversion back to c/s-retinal. This is released by the epithelial cell into the interstitial space from where it is taken up by the photoreceptor cell. This c/s-retinal then associates with the protein opsin to produce the light-sensitive rhodopsin to initiate another cycle. The division of labour between the two cells may be necessary to provide different NADH/NAD concentration ratios in the two cells. A high ratio is necessary in the photoreceptor cell to favour reduction of retinal and a low ration in the epithelial cell for the oxidation reaction (Appendix 9.7).

Chabardes developed a process for the preparation of vitamin A and its intermediates, from cyclogeranylsulfone and Cio aldehyde-acetals [30]. For example, chlorocitral reacted with ethylene glycol, HC(OMe)3 and pyridinium tosylate to provide the chloroacetal (40%), as a mixture of two isomers. Reaction of this allylchloride with A-methylmorpholine oxide (NMO) and Nal furnished the aldehyde, as a mixture of four isomers. These compounds underwent condensation with P-cyclogeranylsulfone. Further chlorination of the sulfone-alkoxide salts, led to a mixture of sulfone-chloride acetals and their products of hydrolysis in 45-50% yield. Double elimination of the chloride and the sulfone, followed by hydrolysis with pyridinium tosylate (PPTS) gave retinal, as a mixture of all E and 13Z isomers (78/22). The overall yield from the chloroacetal was 18%. In another one-pot example, retinal was obtained in 52% yield from the aldehyde, and was then isomerised and reduced to retinol (all E 95.5, 13Z 4, 9Z 0.5) Fig. (8). 

A short synthesis of retinal was described by Taylor et al. [42] based on the addition of a C]3 vinylalane to a methylpyrylium salt. The 13Z-retinal (48%) was isomerised to all E retinal by a previous procedure [43]. P-Ionone was first converted into the alkyne and then into the vinylalane, using the Negishi methodology [44], Addition of an excess of this alane to 4-methylpyrilium tetrafluoroborate [45] gave 13Z-retinal, being isomerized to the all E isomer (L in benzene/ether), Fig. (18). 

A similar route was patented by Ancel and Meilland [66], The ethynyl-retro-ionol was acetylated (Ac20-DMAP-Et3N) and this propargylic acetate was reacted with methyl butadiene acetate in the presence of BF3-Et20. The allenic-retinal, obtained in 61% yield was isomerised in retinal by HBr in acetone (yield 50%), Fig. (34). 

The role of retinal (18, vitamin A aldehyde) in the visual process, involving cis/trans isomerisation of the sterically hindered C-11,12 double bond, is well established [28,29]. Besides the important function of retinal in visual signal transduction in animals is the function of energy production in halophilic bacteria, where the retinal-based bacterio-rhodopsin takes part in a light driven proton pump [30]. 

In mammals, (1IZ)-Retinal, generated from retinol in the retina, is the photo-reactive chromophore, which forms a Schiff-base to a lysine residue of opsin, a G-protein-coupled receptor (GPCR) protein, to give rhodopsin. This visual purple is concentrated in the outer parts of the rod and cone photoreceptors. Upon light absorption, the chromophore converts photons into a chemical signal by isomerisation to (all )-retinal, which causes a conformational change of... 

Apo-jS-carotenal, ethyl 8 -apo- -carotenoate and citranaxanthin are readily accessible by this modular synthesis. The central building block is ll -apo- -carotenal, which itself may be synthesised in diverse ways by Wittig reactions from the intermediates mentioned above. Of particular appeal is a synthesis, wh ich starts from retinol. First, the retinol is oxidised to retinal by an Oppenau-er or TEMPO oxidation. Successive reactions of retinal with Cs-phosphonium salts or phosphonate esters, followed by isomerisation, lead to 8 - po-)8-carotenal and ethyl 8 -apo-yS-carotenoate. Citranaxanthin is obtained by an aldol condensation of 8 -flpo-yS-carotenal with acetone. [55]... 

Recent studies [1293, 1294] have also served to elucidate the relationship between rhodopsin and retinochrome. It would now appear that after incident light has isomerised the ll-cw-retinal unit of rhodopsin into the dl -trans-con-... 

Fig. 1.1 In the first step of vision, light-sensitive cells in the eye are activated when light induces the isomerisation of the pigment 11-cis retinal to all-tranr retinal...

The cis-trans isomerisation of retinal is concerned also in photochemical change in some bacteria where the membrane chromatophore is the protein bacteriorhodopsin. The chain of reactions following absorption of a photon has been studied by time-resolved laser flash spectrometry. The overall reaction has a half-life of about 10 ms, but there are several intermediate reactions with rise times of femtoseconds to milliseconds. In one of these a proton is transferred across bacteriorhodopsin this leads to an electrochemical proton-concentration gradient across the membrane, which is used by the bacterium as a driving force for ATP synthesis [57]. Since the structure of bacteriorhodopsin is known, it is a useful system for the study of membrane transport. 

The photosensitive compounds present in Human and most other mammals are two proteins-opsin and retinal. Out of these two proteins retinal act as receptor of photon and use to give geometrical isomerisation. 

The photochemistry of vision is triggered by absorption of a photon and induces cis-trans isomerisation. The conjugated polyenal, ll-c/s-retinal and the protein opsin combine in retina to give the red-purple 11-cis- amine, rhodopsin. 

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