Enzymatic Preparation of an (S)-Amino Acid from a Racemic Amino Acid

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• 作者：Yijun Chen ; Steven L. Goldberg ; Ronald L. Hanson ; William L. Parker ; Iqbal Gill ; Thomas P. Tully ; Michael A. Montana ; Animesh Goswami ; Ramesh N. Patel
• 刊名：Organic Process Research & Development
• 出版年：2011
• 出版时间：January 21, 2011
• 年：2011
• 卷：15
• 期：1
• 页码：241-248
• 全文大小：178K
• 年卷期：v.15,no.1(January 21, 2011)
• ISSN：1520-586X

文摘

The (S)-amino acid, (S)-2-amino-3-(6-o-tolylpyridin-3-yl)propanoic acid (3), is a key intermediate needed for synthesis of an antidiabetic drug candidate. Three enzymatic routes to 3 were explored. (S)-Amino acid 3 could be prepared in 73% isolated yield with 99.9% ee from racemic amino acid 1 using (R)-amino acid oxidase from Trigonopsis variabilis expressed in Escherichia coli in combination with an (S)-aminotransferase using (S)-aspartate as amino donor. The (S)-aminotransferase was purified from a soil organism identified as Burkholderia sp. and cloned and expressed in E. coli. (S)-Amino acid 3 with 100% ee was also prepared in 68% solution yield and 54% isolated yield from 1 using recombinant (R)-amino acid oxidase from T. variabilis and an (S)-amino acid dehydrogenase from Sporosarcina ureae. The cofactor NADH required for the reductive amination reaction was regenerated using formate and formate dehydrogenase. The chemoenzymatic dynamic resolution of 1 by (R)-selective oxidation with Celite-immobilized (R)-amino acid oxidase in combination with chemical imine reduction using borane鈭抋mmonia complex gave an 81% solution yield and 68% isolated yield of 3 with 100% ee.