Resolution of racemic 1-azido-3-aryloxy-2-propanols by lipase-catalyzed enantioselective acetylation (original) (raw)
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Lipase-catalyzed kinetic resolution of racemic 1-heteroarylethanols—experimental and QM/MM study
Tetrahedron-asymmetry, 2008
The kinetic resolution of racemic 1-(benzothiazol-2-yl)ethanol rac-2a, 1-(benzo[b]thiophen-2-yl)ethanol rac-2b, 1-(benzo[b]furan-3-yl)ethanol rac-2c and 1-(benzo[b]thiophen-3-yl)ethanol rac-2d was studied by enantiomer selective acylation catalyzed by a selection of commercially available and in house produced lipases. Alcoholysis of the corresponding racemic acetates rac-3a–d catalyzed by Candida antarctica lipase B (CaLB) was also investigated. Two racemic 1-heteroarylethanols rac-2a,b were prepared by addition of the corresponding lithiated heteroarylic compounds 1a,b to acetaldehyde, whereas two others, rac-2c,d were synthesized by the addition of MeMgI onto the corresponding heteroaryl-carbaldehydes 1c,d. The high enantiomer selectivities of CaLB in the acylation of racemic 1-heteroarylethanols rac-2a–d allowed the determination of the enantiomeric preference of these enzymatic acetylation reactions by QM/MM [pm3/uff or hf(3-21+g∗∗)/uff] calculations. For acetylation of each of the racemic alcohols rac-2a–d, four possible tetrahedral intermediate states were compared and analyzed.(S)-1-(Benzo[d]thiazol-2-yl)ethanolC9H9NOSEe = 97% (by GC analysis)[α]D25=-18.4 (c 1.0, CHCl3)Source of chirality: lipase-catalyzed kinetic resolutionAbsolute configuration: (S)(S)-1-(Benzo[b]thiophen-2-yl)ethanolC10H10OSEe = 99% (by GC analysis)[α]D25=-21.2 (c 1.0, CHCl3)Source of chirality: lipase-catalyzed kinetic resolutionAbsolute configuration: (S)
2005
Candida rugosa lipase, catalyzed enantioselective acetylation reactions have been performed on novel (±)-3arylmethyl-3-hydroxymethyl-2,3-dihydrobenzopyran-4-ones in diisopropyl ether. The Candida rugosa lipase-catalyzed acetylations exhibit the enantiomeric separation of the racemic compounds 5a-g, the enantioselectivity of the reaction has been found to be highly dependent on the structure of the substrate. The enantiomeric excess (ee) values are determined by 1 H NMR spectral analysis of their O-acetylmandelic acid esters and highest enantiomeric excess obtained is 79% in case of 5c.
Synthetic Communications, 1998
The kinetic resolution of racemic 1-(benzothiazol-2-yl)ethanol rac-2a, 1-(benzo[b]thiophen-2-yl)ethanol rac-2b, 1-(benzo[b]furan-3-yl)ethanol rac-2c and 1-(benzo[b]thiophen-3-yl)ethanol rac-2d was studied by enantiomer selective acylation catalyzed by a selection of commercially available and in house produced lipases. Alcoholysis of the corresponding racemic acetates rac-3a-d catalyzed by Candida antarctica lipase B (CaLB) was also investigated. Two racemic 1-heteroarylethanols rac-2a,b were prepared by addition of the corresponding lithiated heteroarylic compounds 1a,b to acetaldehyde, whereas two others, rac-2c,d were synthesized by the addition of MeMgI onto the corresponding heteroaryl-carbaldehydes 1c,d. The high enantiomer selectivities of CaLB in the acylation of racemic 1-heteroarylethanols rac-2a-d allowed the determination of the enantiomeric preference of these enzymatic acetylation reactions by QM/MM [pm3/uff or hf(3-21+g**)/uff] calculations. For acetylation of each of the racemic alcohols rac-2a-d, four possible tetrahedral intermediate states were compared and analyzed.
Lipase catalysis in the optical resolution of 2-amino-1-phenylethanol derivatives
Journal of the Chemical Society, Perkin Transactions 1, 1992
The lipase PSand CCL-catalysed resolution of unsubstituted and N-alkyl substituted 2-amino-Iphenylethanols with 2,2,2-trifluoroethyl butyrate or with butyric anhydride and those of the corresponding diacylated 1,2-amino alcohols with 1 -alcohols in organic media have been studied. The enzymatic deacylation of diacylated 2-amino-I -phenylethanol stops at approximately 50% conversion yielding the two enantiomers with an e.e. of the order of 100%. Enantioselectivity in the case of N-alkyl substituted compounds is only somewhat lower. Also the enzymatic acylation of 2amino-I -phenylethanol shows high enantioselectivity when the protection of the NH, group with C0,Et or CO,CH,Ph has been used. However, the direct acylation of 2-amino-I -phenylethanol or of its N-alkyl substituted derivatives are slow, the reactions stop before 40% conversion and nonenzymatic aminolysis is usually significant.
Resolution of 3-α-naphthoxy-1,2-propanediol using Candida antarctica lipase
1999
The stereochemistry of the Candida antarctica lipase B (CALB) catalyzed resolution of diacetate 1 or diol 4 was analyzed. The primary and secondary acetate hydrolyses were studied separately using monoacetates 2 and 3. The enantioselectivity of CALB was found to be lower towards primary rather than secondary acetates/alcohols. The steric course of the process is discussed.
Journal of Molecular Catalysis B: Enzymatic, 2001
. The enantioselectivity, E, of Candida antarctica lipase B CALB was found to be strongly influenced by the chain length of the achiral acyl donor employed in the transesterification of 3-methyl-2-butanol. Of the four studied acyl donors, the longest, vinyl octanoate, afforded the highest enantioselectivity. This was true over the temperature range studied, 6-708C. Measurements of the temperature dependence of E allows for separation of the enthalpic and entropic components of enantioselectivity. Changes in E with chain length were mainly caused by changes in the entropic component except for the reaction with vinyl propionate, which differed from the others also in the enthalpic component. Optimisation of acyl donor adds one more possibility to improve the yield of enantiopurity in the production of optically active compounds apart from optimisation of solvent, temperature, water activity, and choice of enzyme. q
New Biotechnology, 2010
Enzyme preparations of Candida antarctica B lipase (CAL-B) -immobilized on Eupergit C and partially modified Eupergit C supports -were tested for kinetic resolution of (R/S)-propranolol, using vinyl acetate as acyl donor, and toluene as organic solvent. The effects of (R/S)-propranolol concentration, vinyl acetate concentration and biocatalyst loading on the esterification and resolution of propranolol were studied. Additionally, different types of immobilized lipase derivatives were also evaluated in terms of its selectivity on kinetic resolution of (R,S)-propranolol. These derivatives showed different enantiomeric ratios (E), with high enantiomeric ratios (E = 57) with CAL-B immobilized on Eupergit C supports.
Tetrahedron-asymmetry, 2001
Both (R)-and (S)-enantiomers of 3-aryloxy-1-nitrooxypropan-2-ols (R)-(−)-1, (S)-(+)-2 were prepared in high enantiomeric excess by lipase from Pseudomonas cepacia (Amano PS) or Pseudomonas fluorescens (Amano AK)-catalyzed acetylation of racemic alcohols 1a-g with vinyl acetate in n-hexane at 4 or 22°C. The enantioselectivity of this transformation was dependent on the substitution pattern of the aryl ring with E-values ranging from 31 to 111.