Deracemization of diastereomerically pure syn- and anti-α-substituted β-hydroxyesters by Novozyme 435 lipase and determination of their absolute configuration by NMR spectroscopy

Abstract Enantiomerically pure α-substituted β-hydroxyesters are important chiral building blocks for ligands, auxiliaries and β-lactam antibiotics. A two-step chemo-enzymatic procedure using lipase as biocatalyst is an efficient way to synthesize such products. To date, the methods described limited molecules that do not contain a center adjacent racemic carbinol, furthermore, they acylation. Here, we investigated deracemization of diastereomerically syn- anti-α-substituted containing two stereo centers, experimental under neat conditions classical molecule dynamics (MD) simulation. screening free immobilized commercial lipases identified B from Candida antarctica (Novozyme 435) most appropriate sterically demanding β-hydroxyesters. Using Novozyme 435, reaction were optimized hydroxyesters (3S) or (3R) achieved with enantiomeric excesses up ≥99% ee maximum overall yields 80%. The absolute configuration enantiomers was eventually determined by 1H-NMR spectroscopy after derivatization Mosher's reagent (α-methoxy-α-trifluoromethylphenylacetic acid = MTPA).