利用固定化青霉素酰胺酶高效酶促合成（S）-α-氨基-4-氟苯乙酸。
Efficient chemoenzymatic synthesis of (S)-α-amino-4-fluorobenzeneacetic acid using immobilized penicillin amidase.
机构信息
Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China; Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China.
Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China; Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China.
出版信息
Bioorg Chem. 2018 Oct;80:174-179. doi: 10.1016/j.bioorg.2018.06.020. Epub 2018 Jun 15.
An efficient chemoenzymatic route was developed for synthesis of (S)-α-amino-4-fluorobenzeneacetic acid, a valuable chiral intermediate of Aprepitant, using immobilized penicillin amidase catalyzed kinetic resolution of racemic N-phenylacetyl-4-fluorophenylglycine. The optimum temperature, pH and agitation rate of the reaction were determined to be 40 °C, 9.5 and 300 rpm, respectively. Kinetic resolution of 80 g LN-phenylacetyl-4-fluorophenylglycine by immobilized amidase 20 g L resulted in 49.9% conversion and >99.9% e.e. within 3 h. The unreacted N-phenylacetyl-4-fluorophenylglycine can be easily racemized and then recycled as substrate. The production of (S)-α-amino-4-fluorobenzeneacetic acid was further amplified in 1 L reaction system, affording excellent conversion (49.9%) and enantioselectivity (99.9%). This chemoenzymatic approach was demonstrated to be promising for industrial production of (S)-α-amino-4-fluorobenzeneacetic acid.
开发了一种高效的化学酶法路线，用于合成（S）-α-氨基-4-氟苯乙酸，这是阿瑞匹坦的一种有价值的手性中间体，使用固定化青霉素酰胺酶催化外消旋 N-苯乙酰基-4-氟苯甘氨酸的动力学拆分。确定了反应的最佳温度、pH 值和搅拌速度分别为 40°C、9.5 和 300rpm。固定化酰胺酶 20g/L 拆分 80g/LN-苯乙酰基-4-氟苯甘氨酸，3 小时内转化率达到 49.9%，ee 值大于 99.9%。未反应的 N-苯乙酰基-4-氟苯甘氨酸可以很容易地外消旋，然后作为底物回收。（S）-α-氨基-4-氟苯乙酸的生产在 1L 反应体系中进一步放大，转化率（49.9%）和对映选择性（99.9%）均优异。这种化学酶法方法有望用于（S）-α-氨基-4-氟苯乙酸的工业生产。
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