Sequential use of regio- and stereoselective lipases for the efficient kinetic resolution of racemic 1-(5-phenylfuran-2-yl)ethane-1,2-diols

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.

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(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)

(R)-1-(5-(2-Chlorophenyl)furan-2-yl)ethane-1,2-diyl diacetateC16H15ClO5Ee = 97% on Chiralpak AS-H HPLC column[α]D25=+33.1 (c 0.5, CHCl3)Source of chirality: lipase mediated kinetic resolutionAbsolute configuration: (R)

(R)-1-(5-(4-Bromophenyl)furan-2-yl)ethane-1,2-diyl diacetateC16H15BrO5Ee = 97% on Chiralpak AS-H HPLC column[α]D25=+42.1 (c 0.5, CHCl3)Source of chirality: lipase mediated kinetic resolutionAbsolute configuration: (R)

(R)-1-(5-(2-Nitrophenyl)furan-2-yl)ethane-1,2-diyl diacetateC16H15NO7Ee = 93% on Chiralpak AS-H HPLC column[α]D25=+82.3 (c 0.5, CHCl3)Source of chirality: lipase mediated kinetic resolutionAbsolute configuration: (R)

(R)-1-(5-(4-Nitrophenyl)furan-2-yl)ethane-1,2-diyl diacetateC16H15NO7Ee = 92% on Chiralpak IB HPLC column[α]D25=+65.5 (c 0.5, CHCl3)Source of chirality: lipase mediated kinetic resolutionAbsolute configuration: (R)