An efficient chemoenzymatic method to prepare optically active O-methyl-l-serine

O-Methyl-l-serine and its derivatives are relevant in peptide synthesis (food, pharmaceuticals, and cosmetics). Optically active O-methyl-l-serine was prepared using a chemoenzymatic method from inexpensive acrylamide. Our method is a four step reaction sequence; bromination of acrylamide; etherification of dibromopropionamide; ammonolysis of α-bromo-β-methoxy-propionamide; enzymatic racemization; and selective hydrolysis. The double-enzyme catalyst system, which consists of α-amino-ε-caprolactam racemase (Locus, E01594) and peptidase B (Locus, D84499), was successfully applied to produce enantiopure O-methyl-l-serine (ee >99.9%) in high yield (>99.7%). Optically active O-methyl-l-serine was obtained with a total yield of 82.4%.

Chemoenzymatic preparation of optically O-methyl-l-serine.Figure optionsDownload as PowerPoint slide

O-Methyl-l-serineC4H9NO3[α]D25=+14.1 (c 1, 6 mol/l HCl)Source of chirality: the precursorAbsolute configuration: (2S)