Chemoenzymatic synthesis of diastereomeric ethyl γ-benzyl paraconates and determination of the absolute configurations of their acids

Enantiopure (99% ee) cis- and trans-γ-benzylparaconic acids and their ethyl esters were synthesized by a procedure involving kinetic enzymatic resolution of the corresponding lactonic esters with α-chymotrypsin (α-CT) with acetone added as a cosolvent. Their absolute configurations were determined by 1H NMR analysis of their 1-(9-anthryl)-2,2,2-trifluoroethyl esters.

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(2R,3R)-2-Benzyltetrahydro-5-oxo-3-furancarboxylic acidC12H12O4Ee = >99%[α]D25=+125.6 (c 0.16, CH3OH)Source of chirality: enzymatic resolutionAbsolute configuration: (2R,3R)

(2S,3R)-2-Benzyltetrahydro-5-oxo-3-furancarboxylic acidC12H12O4Ee = >99%[α]D25=-49.0 (c 0.20, CH3OH)Source of chirality: enzymatic resolutionAbsolute configuration: (2S,3R)

Ethyl (2S,3S)-2-benzyltetrahydro-5-oxo-3-furancarboxylateC14H16O4Ee = 99%[α]D25=-79.4 (c 0.34, CH3OH)Source of chirality: enzymatic resolutionAbsolute configuration: (2S,3S)

Ethyl (2R,3S)-2-benzyltetrahydro-5-oxo-3-furancarboxylateC14H16O4Ee = >99%[α]D25=+19.6 (c 0.24, CH3OH)Source of chirality: enzymatic resolutionAbsolute configuration: (2R,3S)

(1′R,2R,3R)-1-(9-Anthryl)-2,2,2-trifluoroethyl 2-benzyltetrahydro-5-oxo-3-furancarboxylateC28H21F3O4Ee = >99%[α]D25=+86.7 (c 0.15, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1′R,2R,3R)

(1′S,2R,3R)-1-(9-Anthryl)-2,2,2-trifluoroethyl 2-benzyltetrahydro-5-oxo-3-furancarboxylateC28H21F3O4Ee = >99%[α]D25=+95.6 (c 0.25, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1′S,2R,3R)

(1′R,2S,3R)-1-(9-Anthryl)-2,2,2-trifluoroethyl 2-benzyltetrahydro-5-oxo-3-furancarboxylateC28H21F3O4Ee = >99%[α]D25=+7.7 (c 0.13, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1′R,2S,3R)

(1′S,2S,3R)-1-(9-Anthryl)-2,2,2-trifluoroethyl 2-benzyltetrahydro-5-oxo-3-furancarboxylateC28H21F3O4Ee = >99%[α]D25=-22.5 (c 0.40, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1′S,2S,3R)

(1′R,2S,3S)-1-(9-Anthryl)-2,2,2-trifluoroethyl 2-methyltetrahydro-5-oxo-3-furancarboxylateC22H17F3O4Ee = >99%[α]D25=-72.6 (c 0.72, CHCl3)Source of chirality: baker’s yeast reductionAbsolute configuration: (1′R,2S,3S)

(1′S,2S,3S)-1-(9-Anthryl)-2,2,2-trifluoroethyl 2-methyltetrahydro-5-oxo-3-furancarboxylateC22H17F3O4Ee = >99%[α]D25=-36.3 (c 0.60, CHCl3)Source of chirality: baker’s yeast reductionAbsolute configuration: (1′S,2S,3S)

(1′R,2S,3R)-1-(9-Anthryl)-2,2,2-trifluoroethyl 2-methyltetrahydro-5-oxo-3-furancarboxylateC22H17F3O4Ee = >99%[α]D25=-8.5 (c 0.20, CHCl3)Source of chirality: baker’s yeast reductionAbsolute configuration: (1′R,2S,3R)

(1′S,2S,3R)-1-(9-Anthryl)-2,2,2-trifluoroethyl 2-methyltetrahydro-5-oxo-3-furancarboxylateC22H17F3O4Ee = >99%[α]D25=-1.9 (c 0.26, CHCl3)Source of chirality: baker’s yeast reductionAbsolute configuration: (1′S,2S,3R)