Lipase Catalysed Kinetic Resolution of 2-Nitroalcohol: Total Synthesis of Taxol Side Chain and (-)-Bestatin (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)
Tetrahedron-asymmetry, 2011
Possible routes for the enzymatic transformation of various substituted 1-(5-phenylfuran-2-yl)ethane-1,2-diols and their mono- and diacetylated counterparts were studied. Combining the regioselectivity of LPS mediated acylation of the starting racemic diols, the stereoselectivity of LAK shown in the enantiomer selective transformation of the previously formed racemic primary acetates and the LPS mediated mild hydrolysis–alcoholysis of the resolution products, an efficient preparative scale procedure for the synthesis of various highly enantiomerically enriched (R)- and (S)-phenylfuran-2-yl-ethane-1,2-diols has been developed.(S)-2-(5-(2-Chlorophenyl)furan-2-yl)-2-hydroxyethyl acetateC14H13ClO4Ee = 97% on Chiralpak AS-H HPLC column[α]D25=-6.7 (c 0.5, CHCl3)Source of chirality: lipase mediated kinetic resolutionAbsolute configuration: (S)(S)-2-(5-(4-Bromophenyl)furan-2-yl)-2-hydroxyethyl acetateC14H13BrO4Ee = 96% on Chiralpak AS-H HPLC column[α]D25=-10.4 (c 0.5, CHCl3)Source of chirality: lipase mediated kinetic resolutionAbsolute configuration: (S)(S)-2-Hydroxy-2-(5-(2-nitrophenyl)furan-2-yl)ethyl acetateC14H13NO6Ee = 95% on Chiralpak AS-H HPLC column[α]D25=-23.8 (c 0.5, CHCl3)Source of chirality: lipase mediated kinetic resolutionAbsolute configuration: (S)(S)-2-Hydroxy-2-(5-(4-nitrophenyl)furan-2-yl)ethyl acetateC14H13NO6Ee = 93% on Chiralpak IB HPLC column[α]D25=-18.7 (c 0.5, CHCl3)Source of chirality: lipase mediated kinetic resolutionAbsolute configuration: (S)