Application of a modified Mosher’s method for the determination of enantiomeric ratio and absolute configuration at C-3 of chiral 1,3-dihydroxy ketones

The enantiomeric ratio and absolute configuration of products of the transketolase reaction are typically determined by comparison of the specific rotation or derivatisation and HPLC or GC. A Mosher’s ester method has been developed via ester formation at the primary alcohol C-1 which can be used to determine the stereoselectivity of the reaction, as well as the absolute configuration of the product at C-3.

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(2R,3′S) 3,3,3-Trifluoro-2-methoxy-2-phenylpropionic acid 3′-hydroxy-2′-oxo-pentyl esterC15H17F3O5De = 55% [(2R,3′S)-major isomer, (2R,3′R) present][α]D20=+13.3 (c 0.15, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (2R,3′S)

(2S,3′S) 3,3,3-Trifluoro-2-methoxy-2-phenylpropionic acid 3′-hydroxy-2′-oxo-pentyl esterC15H17F3O5De = 55% [(2S,3′S)-major isomer, (2S,3′R) present][α]D20=-37.0 (c 0.1, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (2S,3′S)

(2R,3′S) 3,3,3-Trifluoro-2-methoxy-2-phenylpropionic acid 3′,4′-dihydroxy-2′-oxo-butyl esterC14H15F3O6De = >95% (2R,3′S)[α]D20=+10.2 (c 0.4, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (2R,3′S)

(2S,3′S) 3,3,3-Trifluoro-2-methoxy-2-phenylpropionic acid 3′,4′-dihydroxy-2′-oxo-butyl esterC14H15F3O6De = >95% (2S,3′S)[α]D20=-14.4 (c 0.5, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (2S,3′S)

(2R,3′S) 3,3,3-Trifluoro-2-methoxy-2-phenylpropionic acid 3′-hydroxy-4′-methoxy-2′-oxo-butyl esterC15H17F3O6De = 57% [(2R,3′S)-major isomer, (2R,3′R) present][α]D20=+23.2 (c 0.25, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (2R,3′S)

(2S,3′S) 3,3,3-Trifluoro-2-methoxy-2-phenylpropionic acid 3′-hydroxy-4′-methoxy-2′-oxo-butyl esterC15H17F3O6De = 57% [(2S,3′S)-major isomer, (2S,3′R) present][α]D20=-10.6 (c 0.25, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (2S,3′S)

(3S)-1,3-Dihydroxy-4-methoxybutan-2-oneC5H10O4Ee = 57% [(3S)-major isomer][α]D20=+2.0 (c 2.0, CHCl3)Source of chirality: biocatalysisAbsolute configuration: (3S)