Preparation of 11,14‐epoxy‐bridged and isomeric chain‐demethylated retinals. 13‐Demethyl‐11,14‐epoxy‐, 9‐demethyl‐, 13‐demethyl‐ and 9,13‐bisdemethyl‐retinals

Abstract

1 p1 of 10 mM oxalic acid. To some samples, valinomycin was added in such a concentration (2 pI of the 0.1 mg/ml solution) that the steady state value of the proton transport was i n c r e a~e d '~. To each sample, nigericin was added in such an amount ( I pI of the 0.1 mg/ml solution) that the AjiH of the membrane was destroyed 14. l 4 K . HellinywerS, Ph. D. Thesis, Amsterdam (1979).Preparation of 11,14-epoxy-bridged and isomeric chain-demethylated retinals. 13-Demethyl-ll,14-epoxy-, 9-demethyl-, 13-demethyl-and 9,13-bisdemethyl-retinals Abstract. 9-Cis-and all-trans-l3-demethyl-l I , 14-epoxyretinyl acetate were prepared via a Wittig coupling between P-ionylidenetriphenylphosphonium bromide (1) and 5-(acetoxymethyl)furfural. Saponification of these acetates, subsequent oxidation and HPLC separation afforded pure 9-cisand all-trans-] 3-demethyl-1 1,lCepoxyretinal. 1 1-Cis-and all-trans-9-demethyl-, 13-demethyl-and 9,13-bisdemethyl-retinaI were prepared via the same scheme, based on the Pommer vitamin A acetate synthesis. Their photochemistry shows the same type of solvent dependence as retinal. HPLC separation of the photostationary mixtures of these retinals yielded the all-trans, 13-, I I-, 9-and 7-cb isomers in 98% purity. IntroductionIn the preceding paper' we described the preparation of modified bacteriorhodopsins by the reaction of 13-demethyl-] 1,14-epoxyretinal and geometric isomers of 9--demethyl-, 13-demethyl-and 9,13-bisdemethylretinals with bacterioopsin. Investigations into the possible light--driven proton pump action and light/dark adaptation of these pigment analogues led to new information concerning the conformation of the chromophore and the process of proton pumping. In this paper, the syntheses of the required retinals are described. A simple method, based on the Wittig reaction, is given for the preparation of all-trans-and 9-cis-13--demethyl-1 1,14-epoxyretinal. For the synthesis of all--trans-and 1 l-cis-9-demethyl, 13-demethyl-and 9,13-bisdemethylretinal, we applied the Wittig reaction. The isomers were separated by preparative HPLC. Irradiation of the all-trans isomer of the demethylated retinals in a suitable solvent gives rise to photostationary mixtures of 7-, 9-, 11-and 13-cis isomers from which preparative amounts with over 98 % chemical purity could be isolated by HPLC. SynthesisFor the preparation of 9-cis-13-demethyl-l l ,14-epoxyretinal (5) and all-trans-13-demethyl-l l, 14-epoxyretinal (6) we used the approach depicted in Scheme 1. The synthesis of the Wittig salt 1, starting from j3-ionone, has been previously described*. 5-(Acetoxymethyl)furfural (2) is commercially available. The Wittig coupling between 1 and 2, using butyllithium as base, gives a I : I mixture of the bridged retinyl acetates 3 and 4. Saponification of 3 and 4 and subsequent oxidation with MnO, affords a I : 1 mixture of the 11,14-epoxy-bridged retinal 5 and 6 (overall yield 78 %). Both retinals could be separated by HPLC into pure 5 and 6. They were characterized by 'H N M R spectroscopy, NOE difference ...

Microsecond atomic force sensing of protein conformational dynamics: Implications for the primary light-induced events in bacteriorhodopsin

“…29). The specific choices were artificial pigments (I, II, and III) formed from three locked retinal analogs 1,2 (30) and 3 (31,32), in which the critical C 13 AC 14 isomerization is blocked by a 5-membered ring structure. Although pigment I shows transient absorbance and fluorescence changes on a picosecond time scale (4), all three pigments do not exhibit any of the microsecondmillisecond changes in the chromophore absorption spectrum, which characterize the photocycle of native bR (4,28,32,33).…”

Retinal Analog Study of the Role of Steric Interactions in the Excited State Isomerization Dynamics of Rhodopsin

“…The synthesis of 13-demethylretinal was accomplished by a Horner-Wadsworth-Emmonds (HWE) coupling of 3-cyano-2-propenyl diethylphosphonate with all-trans--ionylidene acetaldehyde and subsequent reduction of the nitrile function with Dibal-H. Purification of the all-trans isomer was accomplished by silica gel chromatography (eluent was 20:80 diethyl ether/petroleum ether). The spectroscopic characteristics of all-trans-13-demethyl retinal are in agreement with the literature (Broek et al, 1983). 11-cis-13-Demethylretinal was prepared by photoisomerization of the all-trans isomer as described before (Broek et al, 1983).…”

9‐Demethyl‐9‐haloretinals by Wadsworth−Emmons Coupling − Easy Preparation of Pure (all‐E), (9Z) and (11Z) Isomers

“…In many cases the photostationary state is also dependent on the substitution pattern, such that not all mono Z derivatives are present in sufficient amount in the photostationary state. [16] In this paper we describe a strategy in which the same starting material is used to prepare the required halogenated β-ionone derivative as mixtures of (all-E) and (9Z) isomers, which can be simply separated. These materials are used in a WadsworthϪEmmons coupling and final DIBAL-H reduction in such way that pure (all-E) and (9Z) isomers are formed via thermal chemistry only.…”