34356-31-5Relevant articles and documents
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.
Process for preparation of allyl sulfone derivatives and intermediates for the preparation
-
Page 8, (2010/02/06)
The present invention relates to a process for producing an allyl sulfone derivative represented by the formula (3): wherein Ar is an optionally substituted aryl group, and the corrugated line means either one of E/Z geometrical isomers, or a mixture thereof, which is an intermediate for producing vitamin A, which process is characterized by reacting an aryl sulfinic acid or a salt thereof represented by the formula (2): ArSO2M (2) wherein Ar is as defined above, and M is hydrogen atom, sodium atom or potassium atom, with an allyl halide derivative represented by the formula (1): wherein X is a halogen atom, and Ar and the corrugated line are as defined above.
P(CH3NCH2CH2)3N as a dehydrobromination reagent: Synthesis of vitamin A derivatives revisited
Wroblewski, Andrzej E.,Verkade, John G.
, p. 420 - 425 (2007/10/03)
Although P(CH3NCH2CH2)3N (1) was found to be less effective than 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in the removal of hydrogen bromide from vitamin A intermediates 13-cis-10-bromo-9,10-dihydroretinyl acetates (6) and 14-bromo-9,14-dihydroretinyl acetate (11) when the reaction was carried out in refluxing benzene, in acetonitrile at room temperature it was superior to DBN and DBU. A 31P NMR study of this reaction suggests that the carbanion generated from acetonitrile-d3 in the presence of 1 is the basic species that initiates the elimination step. Diastereoselectivity of the nucleophilic addition of (Z)-HC≡ C(CH3)=CHCH20H to the carbonyl group of (E)-2-methyl-4-(2′,6′,6′-trimethyl-1′-cyclohexen- 1′-yl)-3-butenal (2) was only moderate (20%), and (9R*, 10S*)-13-cis-11,12 -didehydro-9,10-dihydro-10-hydroxyretinol (3b) predominated. The LiAlH4 reduction of the C≡C bond in the diastereoisomeric diols 3 afforded 13-cis-9,10-dihydro-10-hydroxyretinols 4a and 4b as major products together with 11-cis-13-cis-isomers and the deoxygenated compound (3EZ,5EZ,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)- 1,3,5,8-nonatetraene (9). Reaction of 15-acetates of the pure diastereoisomeric allylic alcohols 4a and 4b with PBr3 occurred with significant but not identical retention of configuration, and with concomitant formation of the rearranged bromide 11.
