472-86-6Relevant academic research and scientific papers
Femtosecond ultraviolet-visible absorption study of all-trans→13-cis9-cis photoisomerization of retinal
Yamaguchi, Shoichi,Hamaguchi, Hiro-O
, p. 1397 - 1408 (1998)
The all-trans→13-cis9-cis photoisomerization reaction of retinal in aerated nonpolar solvents has been studied by femtosecond time-resolved ultraviolet-visible (UV-VIS) absorption spectroscopy. The excited-state absorption spectra in the wavelength region 400-800 nm indicate that there is no all-trans→13-cis9-cis isomerization reaction pathway that is complete in the electronic excited singlet manifold of S1, S2, and S3. The ground-state bleaching recovery of all-trans retinal monitored in the near UV (ultraviolet) wavelength region 310-390 nm shows that a perpendicular excited singlet state (p*) takes part in the all-trans→13-cis9-cis isomerization reaction. The lifetime of p* is about 7 ps, and the precursor of p* is most probably the S2 state. The isomerization quantum yield derived from the femtosecond UV absorption data agrees well with those determined by the HPLC analysis of the photoproduct. The temperature dependence of the isomerization quantum yield indicates the existence of a potential-energy barrier as high as (1.2±0.6)×103cm-1 on the reaction pathway from the S2 state to the p* state.
The Crystal Structure of 13-cis-Retinal. The Molecular Structures of its 6-s-cis and 6-s-trans Conformers
Simmons, Charles J.,Liu, Robert S. H.,Denny, Marlene,Seff, Karl
, p. 2197 - 2205 (1981)
The crystal and molecular structure of 13-cis-retinal, C20H28O, has been determined by single-crystal X-ray diffraction techniques using counter methods.The structure was refined by full-matrix least-squares procedures using 2762 unique and significant (at the 2? level) reflections to a final weighted R index of 0.062.Triclinic crystals form in the space group P1/ with unit-cell dimensions of a=12.494(6), b=18.279(8), c=7.992(5) Angstroem, α=100.26(4), β=90.26(5), γ=94.35(4) deg, with V=1790(2) Angstroem3, Z=4, Dc=1.055 Mg m-3, Mr=284.4, F(000)=624.The crystal structure discloses the presence of two conformers.In the 6-s-trans conformer, the double bond in the cyclohexene ring lies nearly in the plane of the polyene chain of the molecule, while in the 6-s-cis conformer, the ring is rotated 110 deg from this orientation.Although the greater extent of the conjugated system in the 6-s-trans conformer indicates that it has more resonance stabilization than the 6-s-cis conformer, its intramolecular contacts and distortions show that it also has a higher steric energy.For the two conformers to coexist in the crystal, these two energy differences must nearly balance.
A porous coordination network catalyzes an olefin isomerization reaction in the pore
Ohara, Kazuaki,Kawano, Masaki,Inokuma, Yasuhide,Fujita, Makoto
, p. 30 - 31 (2010)
(Figure Presented) All-trans retinal efficiently diffused into the pore of a porous coordination network consisting of ZnI2 and an electron-deficient triazine-cored ligand. Enclathrated retinal was isomerized into the 13-cis form and easily replaced with all-trans retinal in solution, thus revealing the catalysis of retinal isomerization by the porous network.
Catalytic synthesis of 9-cis-retinoids: Mechanistic insights
Kahremany, Shirin,Kubas, Adam,Tochtrop, Gregory P.,Palczewski, Krzysztof
supporting information, p. 10581 - 10595 (2019/07/22)
The regioselective Z-isomerization of thermodynamically stable all-trans retinoids remains challenging, and ultimately limits the availability of much needed therapeutics for the treatment of human diseases. We present here a novel, straightforward approach for the catalytic Z-isomerization of retinoids using conventional heat treatment or microwave irradiation. A screen of 20 transition metal-based catalysts identified an optimal approach for the regioselective production of Z-retinoids. The most effective catalytic system was comprised of a palladium complex with labile ligands. Several mechanistic studies, including isotopic H/D exchange and state-of-the-art quantum chemical calculations using coupled cluster methods indicate that the isomerization is initiated by catalyst dimerization followed by the formation of a cyclic, six-membered chloropalladate catalyst-substrate adduct, which eventually opens to produce the desired Z-isomer. The synthetic development described here, combined with thorough mechanistic analysis of the underlying chemistry, highlights the use of readily available transition metal-based catalysts in straightforward formats for gram-scale drug synthesis.
Z -isomerization of retinoids through combination of monochromatic photoisomerization and metal catalysis
Kahremany, Shirin,Sander, Christopher Lane,Tochtrop, Gregory P.,Kubas, Adam,Palczewski, Krzysztof
supporting information, p. 8125 - 8139 (2019/09/19)
Catalytic Z-isomerization of retinoids to their thermodynamically less stable Z-isomer remains a challenge. In this report, we present a photochemical approach for the catalytic Z-isomerization of retinoids using monochromatic wavelength UV irradiation treatment. We have developed a straightforward approach for the synthesis of Z-retinoids in high yield, overcoming common obstacles normally associated with their synthesis. Calculations based on density functional theory (DFT) have allowed us to correlate the experimentally observed Z-isomer distribution of retinoids with the energies of chemically important intermediates, which include ground- and excited-state potential energy surfaces. We also demonstrate the application of the current method by synthesizing gram-scale quantities of 9-cis-retinyl acetate 9Z-a. Operational simplicity and gram-scale ability make this chemistry a very practical solution to the problem of Z-isomer retinoid synthesis.
Efficient, low-cost synthesis of retinal (Vitamin A aldehyde)
Hruszkewycz, Damian P.,Cavanaugh, Kathryn R.,Takamura, Kathryn T.,Wayman, Lora M.,Curley Jr., Robert W.
experimental part, p. 2205 - 2207 (2011/09/14)
Inexpensive retinyl acetate has been subjected to transesterification followed by allylic oxidation to give retinal in 98% yield as a 92:8 mixture of all-trans/13-cis isomers after chromatographic separation. More convenient methods of isolating the all-trans isomer have also been employed. Georg Thieme Verlag Stuttgart ? New York.
Cyclopropyl and isopropyl derivatives of 11- cis and 9- cis retinals at C-9 and C-13: Subtle steric differences with major effects on ligand efficacy in rhodopsin
DeGrip, Willem J.,Bovee-Geurts, Petra H. M.,Wang, Yajie,Verhoeven, Michiel A.,Lugtenburg, Johan
body text, p. 383 - 390 (2011/05/30)
Retinal is the natural ligand (chromophore) of the vertebrate rod visual pigment. It occurs in either the 11-cis (rhodopsin) or the 9-cis (isorhodopsin) configuration. In its evolution to a G protein coupled photoreceptor, rhodopsin has acquired exceptional photochemical properties. Illumination isomerizes the chromophore to the all-trans isomer, which acts as a full agonist. This process is extremely efficient, and there is abundant evidence that the C-9 and C-13 methyl groups of retinal play a pivotal role in this process. To examine the steric limits of the C-9 and C-13 methyl binding pocket of the binding site, we have prepared C-9 and C-13 cyclopropyl and isopropyl derivatives of its native ligands and of α-retinal at C-9. Most isopropyl analogues show very poor binding, except for 9-cis-13-isopropylretinal. Most cyclopropyl derivatives exhibit intermediate binding activity, except for 9-cis-13-cyclopropylretinal, which presents good binding activity. In general, the binding site shows preference for the 9-cis analogues over the 11-cis analogues. In fact, 13-isopropyl-9-cis-retinal acts as a superagonist after illumination. Another surprising finding was that 9-cyclopropylisorhodopsin is more like native rhodopsin with respect to spectral and photochemical properties, whereas 9-cyclopropylrhodopsin behaves more like native isorhodopsin in these aspects.
Complex thermal behavior of 11-cis-retinal, the ligand of the visual pigments
Lopez, Carlos Silva,Alvarez, Rosana,Dominguez, Marta,Faza, Olalla Nieto,De Lera, Angel R.
experimental part, p. 1007 - 1013 (2009/07/04)
Upon heating to 80 °C, 11-cis-retinal yields a mixture of all-trans-retinal and 13-cis-retinal. This isomerization has been studied by means of density functional theory methods, and the computational results suggest a close competition between two mechanisms of very different nature. A classical internal rotation around the C11-C12 cis double bond, via a diradical transition state, accounts for the formation of the all-trans isomer. An intricate sequence of pericyclic reactions, namely a reversible [1,7]-H sigmatropic shift and a reversible 6-π-oxa-electrocyclic reaction, is responsible for the formation of 13-cis-retinal. Experiments using 11-cis-retinal labeled with deuterium at C19 confirmed the mechanistic proposal and also revealed an unprecedented outcome on the product composition of isotopologues.
Preparation of 3-bromomethyl-3-butenal diethylacetal and its conversion into isoprenoid aldehydes derivatives
Mineeva,Kulinkovich
experimental part, p. 1623 - 1632 (2010/04/27)
The cyclopropanation of ethyl 3,3-diethoxypropionate with alkoxytitanacyclopropane reagents followed by the cleavage of the three-membered carbocycle in the formed cyclopropyl mesylate provided in a good yield 3-bromomethyl-3-butenal diethylacetal. The la
New syntheses of retinal and its acyclic analog γ-retinal by an extended aldol reaction with a C6 building block that incorporates a C5 unit after decarboxylation. A formal route to lycopene and β-carotene
Valla, Alain,Valla, Benoist,Le Guillou, Regis,Cartier, Dominique,Dufosse, Laurent,Labia, Roger
, p. 512 - 520 (2008/02/07)
Since the C15 β-end-group aldehyde 10 ((β-ionylidene) acetaldehyde), an excellent intermediate in the syntheses of retinoids, can be synthesized in many ways from β-ionone, and since the corresponding acyclic C15 ψ-end-group aldehyde 5 can easily be synthesized from citral (1) (Scheme 3), we applied the C15 + C5 route to the syntheses of γ-retinal ((all-E)-8) (Scheme 3) and retinal ((all-E)-13) (Scheme 4), and therefore, by coupling (2 x C20 → C 40), to the preparation of lycopene (14) and β-carotene (15) (Scheme 5). Our new syntheses of retinal ((all-E)-13) and γ-retinal ((all-E)-8 use an extended aldol reaction with a C6 building block that incorporates a C5 unit after decarboxylation.
