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.
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.
Process for preparation of allyl sulfone derivatives and intermediates for the preparation
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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.
Process for producing retinol and intermediate compounds for producing the same
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Page 14, (2010/01/31)
There are disclosed a disulfone compound of formula (1): wherein Ar denotes an aryl group that may have a substituent, R1 denotes a hydrogen atom or a protective group of a hydroxyl group and the wavy ine means that the disulfone compound is an E or Z geometrical isomer or i mixture thereof,a method for producing the same,intermediate compounds therefore anda process for producing retinol through the disulfone compound.
Ionic Photodissociation of Polyenes via a Highly Polarized Singlet Excited State
Reddy, A. Mahipal,Rao, V. Jayathirtha
, p. 6727 - 6731 (2007/10/02)
Several polyene acetates and polyene methyl ether were prepared.Upon direct excitation these polyenes undergo ionic photodissociation from their singlet excited states.Triplet-sensitization experiments on these polyenes revealed that the ionic photodissociation process is restricted to singlet excited states.The rationale put forward is that the polyene chromophore undergoes charge separation/polarization in the singlet excited state, which leads to ionic photodissociation.
PMR STUDY OF REACTION OF 10,15-DIHYDROXY-9,13-DIMETHYL-7-(1,1,5-TRIMETHYL-5-CYCLOHEX-6-ENYL)-8,11,13-NONATRIENE ACETATES WITH HYDROCHLORIC ACID
Filippova, T. M.,Mairanovskii, V. G.,Shmyrev, I. K.,Gutnikova, N. P.,Zakharova, N. I.,et al.
, p. 2165 - 2175 (2007/10/02)
Dehydration of acetylated 10,15-dihydroxy-9,13-dimethyl-7-(1,1,5-trimethyl-5-cyclohex-6-enyl)-8,11,13-nonatriene by hydrochloric acid gives as intermediate products a mixture of 8-chloro- and 14-chloroacetates whose proportion depends on the solvent used in the reaction.Dehydrochlorination turns 8-chlorine derivatives into 14-chlorine derivatives from which vitamin A acetate is then formed.The precursor of 13-Z-retinyl acetate seems to be 11-E,13-isomer of 8-chloroacetate.A general conversion scheme is proposed and the reaction rate constants are determined.
Preparation of (7Z) - and (7Z,11Z) - Vitamin A
Soukup,Widmer
, p. 4117 - 4118 (2007/10/02)
An efficient access to (7Z)- and (7Z,11Z)-vitamin A is described. Following the addition of a C6-acetylenic building block to 2,6,6-trimethylcyclohexanone (2), dehydration of the tert. alcohol 3 and formation of the C15-Wittig salt, the (7Z)-geometry was introduced by partial hydrogenation of the triple bond over Raney-nickel. Following Wittig reaction with (E)-2-methyl-4-acetoxy-2-butenal gave a mixture of the title compounds 8 and 9 which could easily be separated.
REGIOSELECTIVE PHOTOISOMERISATION OF RETINOLACETATE
Rao, V. Jayathirtha,Bhalerao, U. T.
, p. 3441 - 3444 (2007/10/02)
Regioselective photoisomerisation of retinolacetate undergoing at tri-substituted double bonds upon singlet and triplet excitation and its ionic photodissociation process originating from singlet excited state is reported.
