An efficient chemoenzymatic method to prepare optically active O-methyl-d-serine |
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Authors: | Zhi-Yuan Wang Peng-Mei Lv Zhen-Hong YuanWen Luo Shu-Na Liu |
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Affiliation: | Key Laboratory of Renewable Energy and Gas Hydrate, Guangzhou Institute of Energy Conversion, CAS, Guangzhou 510640, Guangdong, China |
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Abstract: | Lacosamide is an important anti-epilepsy drug and O-methyl-d-serine is a relevant intermediate in the synthesis of lacosamide. Optically active O-methyl-d-serine was prepared by 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 d-stereospecific amino-acid amidase (Locus, AB026907), was successfully applied to produce enantiopure O-methyl-d-serine (ee >99.8%) in high yield (>98.5%). Optically active O-methyl-d-serine was obtained with a total yield of 81.3%. |
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Keywords: | O-Methyl-d-serine Chemoenzymatic method α-Amino-ε-caprolactam racemase d-Stereospecific amino-acid amidase Lacosamide |
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