A Convenient and Stereoselective Synthesis of 11Z-3,4-Didehydroretinal by Horner-Emmons Reaction Using Diphenyl Phosphonate

Abstract

In the visual pigment rhodopsin, the chromophore 11Z-retinal (1, vitamin A 1 aldehyde) binds to the e-amino group of a lysine residue of the apoprotein opsin through a protonated Schiff base.2) Rhodopsin is the G-protein-coupled photoreceptor in the retina of vertebrates that initiates the visual signal transduction cascade in dim light.3) It is a representative G-protein-coupled receptors (GPCRs), and is a member of the superfamily of the seven transmembrane helix proteins, a biologically very significant class of signal mediators.4,5) Some pigments, especially those of fresh water animals, contain 11Z-3,4-didehydroretinal (2, vitamin A 2 aldehyde) as well as 11Z-retinal (1) as the chromophore.6,7) For study of the mechanism of the visual process, a supply of a sufficient amount of the chromophore in pure 11Z-form is essential for the preparation of the pigment. Only one report for the stereoselective synthesis of 11Z-3,4-didehydroretinal (2) using hydrogenation of the acetylenic precursor by Lindlar catalyst has appeared in the literature. 8) In the past decade, methods dealing with a stereoselective synthesis of 11Z-retinal have been developed. [9][10][11] In connection with our stereoselective synthesis of retinoid compounds, 1,12-15) we describe herein a convenient and stereoselective synthesis of 11Z-3,4-didehydroretinal (2) (Chart 1). Results and DiscussionPreviously, we reported a highly stereoselective synthesis of 11Z-retinal (1) from the b-ionone-tricarbonyliron-complex (3) by controlling the stereochemistry of the newly produced double bond via the nitrile (4). 13) Our first approach for the preparation of 11Z-3,4-didehydroretinal (2) was an application of this methodology. However, all our attempts were unsuccessful. Treatment of 3,4-didehydro-b-ionone (7) 16) with dodecacarbonyltriiron in benzene afforded a complex mixture, and the desired tricarbonyliron-complex (8) was not obtained in good yield. The attempted conversion of the silyloxytricarbonyliron-complex (5), derived from 3-silyloxy-bionone, 17) into the 3,4-didehydro-b-ionone-tricarbonylironcomplex (8) was not achieved. Further more, our trials of transformation of the tricarbonyliron-complex (6), prepared according to our reported procedure, 13) into the 3,4-didehydroretinal (2), including the introduction of double bond at the 3 position, was not successful under the various reaction conditions (Chart 2).In the literature, two Horner-Emmons condensations, resulting in the formation of a new double bond predominantly A convenient synthesis of 3,4-didehydroretinal was developed. The Horner-Emmons reaction between 3,4-didehydro-b b-ionone and diphenyl phosphonate in the presence of crown ether gave the retinonitrile as an isomeric mixture, in which the newly produced double bond was predominantly 11Z-form. After separation of the 11Z-form retinonitrile, it was converted into the corresponding retinal in good yield without isomerization of the double bonds.

Visual adaptation in Lake Victoria cichlid fishes: depth-related variation of color and scotopic opsins in species from sand/mud bottoms

“…The amplified DNA fragments were digested with restriction enzymes and cloned into the expression vector pMT5 [ 48 ] for LWS or pFLAG-CMV-5a (Sigma-Aldrich; St. Louis, Missouri, United States) for RH1. The visual pigments were reconstituted with A1- and A2-derived retinal, with A2-derived retinal synthesized as described previously [ 49 ]. Absorption spectra of the pigment solutions in the presence of hydroxyl-amine (<100 mM) before and after photobleaching were recorded using a spectrophotometer (UV-2400; Shimadzu; Kyoto, Japan), with 5–30 measurements before and after photobleaching.…”

Synthesis of One Double Bond-Inserted Retinal Analogs and Their Binding Experiments with Opsins: Preparation of Novel Red-Shifted Channelrhodopsin Variants

“…A1-10ex (4a) and A2-10ex (4b) were prepared from β-ionylideneacetaldehyde (9a) 23) and 3,4-didehydro-βionylideneacetaldehyde (9b) 24) by C2-/C5-elongated sequence (Chart 3). Although A1-14ex (5a) was a known compound as 14′-apo-β-carotenal, which was produced by the oxidative degradation of β,β-carotene, 21) we prepared 5a by the C2elongated sequence from retinal (2a).…”

Synthesis and Use of Stable Isotope Enriched Retinals in the Field of Vitamin A

“…Under these conditions also threo-adduct can form which gives trans isomer by the elimination of diphenyl phosphate salt. In the mean time via this method 3,4-didehydro-11 Z -retinal and 7,8-dihydro-11 Z -retinal have been prepared [ 100 , 101 ].…”