Stereoselective synthesis of optically active cyclitol precursors via a chemoenzymatic method

Racemic α′-acetoxy α,β-unsaturated cyclohexanone has been converted to the corresponding enantiomerically enriched α′-hydroxylated and acetoxylated compounds with 97% ee via enzymatic resolution with PLE. OsO4-Catalyzed dihydroxylation of enantiomerically enriched α′-acetoxylated compound afforded a single diastereomer in 85% chemical yield. The absolute configuration of 2,3,6-triacetoxycylohexanone was determined by X-ray diffraction analysis. Subsequent Luche reduction allowed us to obtain corresponding syn-type cyclitol precursors in a highly stereoselective manner as expected.

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(1R,2R,4S)-(−)-3-Oxocyclohexane-1,2,4-triyl triacetateC12H16O7Ee = 97%[α]D20=-7.25 (c 0.02, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1R,2R,4S)

(1R,2S,3S,4S)-(−)-3-Hydroxycyclohexane-1,2,4-triyl triacetateC12H18O7Ee = 97%[α]D20=-1.3 (c 0.02, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1R,2S,3S,4S)