137121-52-9Relevant articles and documents
Catalytic synthesis of 9-cis-retinoids: Mechanistic insights
Kahremany, Shirin,Kubas, Adam,Tochtrop, Gregory P.,Palczewski, Krzysztof
, p. 10581 - 10595 (2019)
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.
METHOD FOR SYNTHESIS OF 9-CIS-BETA-CAROTENE AND FORMULATIONS THEREOF
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, (2017/12/29)
The present invention relates to a method for total chemical synthesis of 9-cis-β-carotene (9CBC), and further provides stable formulations thereof.
Laser flash photolysis study on the retinol radical cation in polar solvents
El-Agamey, Ali,Fukuzumi, Shunichi
scheme or table, p. 6437 - 6446 (2011/10/10)
Laser flash photolysis (LFP) of retinol in argon-saturated methanol gives rise to a transient at 580 nm (transient A). Formation of transient A is accompanied by a transient growth at 370 nm. The rate of this growth is retinol concentration-dependent. The transient growth at 370 nm was removed in the presence of N2O, which is known to scavenge solvated electrons. These results can be interpreted by formation of retinol+ (λmax = 580 nm) and solvated electrons following LFP of retinol. Subsequently, the solvated electrons are rapidly scavenged by retinol to form retinol- (λmax = 370 nm in methanol). On the other hand, transient A is not ascribed to the retinyl cation, as was previously proposed, because the retinyl cation, generated from LFP of retinyl acetate, and transient A show different reactivities towards halide ions (e.g. kBr = 1.7 × 109 and 1.51 × 1010 M-1 s-1 respectively, in acetonitrile). After demonstrating the identity of transient A as retinol+, its reactions with carotenoids were examined in air-saturated polar solvents. In the presence of carotenoids, an enhancement in the decay of retinol+ was observed and was accompanied by formation of the corresponding carotenoid radical cations via electron transfer from carotenoids to retinol+. Furthermore, the reactivity of retinol+ towards pyridine derivatives was investigated in air-saturated polar solvents. It was found that the decay of retinol + was accelerated with concomitant formation, with the same rate, of a transient at 370 nm. Similar observations were obtained with increasing pH of air-saturated aqueous 2% Triton X-100 of retinol+. The 370 nm (or 380 nm in the case of Triton X-100) transient is attributed to the base adducts or deprotonated neutral radicals. On the basis of these results, the reactivities of the retinyl cation and retinol+ are compared and the consequences of retinol+ formation within biological environments are discussed.
