Chemoenzymatic synthesis of highly enantiomerically enriched secondary alcohols with a thiazolic core

Stereoselective preparative enzymatic acylation and hydrolysis/methanolysis of various C-substituted rac-thiazol-2-yl-methanols were achieved for the preparation of enantiopure or enantiomerically enriched, naturally occurring 2-hydroxymethylthiazoles. The absolute configurations of the resulting secondary alcohols were determined by a detailed 1H NMR study of Mosher’s derivatives.

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tert-Butyl 2-((R)-1-hydroxyethyl)thiazole-4-carboxylateC10H15NO3SEe = 99% on Chiralpak IB HPLC column[α]D20=+24.3 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

tert-Butyl 2-((R)-1-hydroxy-2,2-dimethylpropyl)thiazole-4-carboxylateC13H21NO3SEe = 94% on Chiralpak IB HPLC column[α]D20=+17.1 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

tert-Butyl 2-((R)-1-hydroxy-3-methylbutyl)thiazole-4-carboxylateC13H21NO3SEe = 99% on Chiralpak IC HPLC column[α]D20=+14.4 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

tert-Butyl 2-((R)-1-hydroxydecyl)thiazole-4-carboxylateC18H31NO3SEe = 99% on Chiralpak IA HPLC column[α]D20=+38.1 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

tert-Butyl 2-((S)-hydroxy(phenyl)methyl)thiazole-4-carboxylateC15H17NO3SEe = 93% on Chiralkpak IB HPLC column[α]D20=-3.8 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (S)

(R)-1-(4-Bromothiazol-2-yl)ethanolC5H6BrNOSEe = 99% on Chiralpak IC HPLC column[α]D20=+21.9 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(4-Bromothiazol-2-yl)-2,2-dimethylpropan-1-olC8H12BrNOSEe = 99% on tandem Chiralpak IB-IC HPLC column[α]D20=+63.6 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(4-Bromothiazol-2-yl)-3-methylbutan-1-olC8H12BrNOSEe = 99% on tandem Chiralpak AS-IB HPLC column[α]D20=+35.3 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

tert-Butyl 2-((R)-1-hydroxyallyl)thiazole-4-carboxylateC10H15NOSEe = 88% on Chiralpak IA HPLC column[α]D20=+15.25 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-1-(4-Bromothiazol-2-yl)-2-methylpropan-1-olC7H10BrNOSEe = 99% on tandem Chiralcel OJ-Chiralpak AS HPLC column[α]D20=+29.5 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (R)