Chemoenzymatic synthesis of N-Boc protected (2S,3R)-3-hydroxy-3-methylproline

N-Boc protected 3-hydroxy-2-hydroxymethyl-3-methylpyrrolidine was kinetically resolved by acylation in an organic solvent catalyzed by Pseudomonas fluorescens lipase to give the corresponding acetate and residual diol in 14 E. Further selective oxidation afforded the title compound in high diastereo- and enantioselectivity.

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(2R,3R)-3-Hydroxy-2-hydroxymethyl-3-methyl-pyrrolidine-1-carboxylic acid tert-butyl esterC11H21NO4[α]D22=-24.3 (c 3.0, MeOH)Source of chirality: enzymatic kinetic resolutionee: 78% (chiral GC as monoacetate)Absolute configuration: 2R,3R

(2R,3R)-2-Acetoxymethyl-3-hydroxy-3-methyl-pyrrolidine-1-carboxylic acid tert-butyl esterC13H23NO5[α]D22=-18.5 (c 2.0, CH2Cl2)Source of chirality: enzymatic kinetic resolutionee: 80% (chiral GC)Absolute configuration: 2R,3R

(2S,3R)-1-(tert-Butoxycarbonyl)-3-hydroxy-3-methylprolineC11H19NO5[α]D22=-19.5 (c 1.34, MeOH)Source of chirality: enzymatic kinetic resolutionee: 99% (chiral GC as methyl ester)Absolute configuration: 2S,3R