Efficient synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol at high substrate load using car

• 作 者: KanglingChen;JinpingLin;
• 机 构: State Key Laboratory of Bioreactor Engineering, Department of Bioengineerng, East China University o
• 出 处: 2015年上海市研究生学术论坛(生物化工)
• 发表日期: 2015年期

　　(R)-[3,5-bis(trifluoromethyl)phenyl] ethanol [(R)-BTPE] is a valuable chiral intermediate product for the synthesis of a neurokinin-1 receptor antagonist, such as Aprepitant (Emend(R)) and Fosaprepitant (Ivemend(R)).An NADPH-dependent carbonyl reductases (LkCR) from Lactobacillus kefir was gained by screening.It was confirmed to have a good ability to produce (R)-BTPE from 3,5-bis(trifluoromethyl)actophennone (3,5-BTAP) with excellent anti-Prelog stereoselectivity.Then the carbonyl reductases LkCR was coupled with glucose dehydrogenase in Escherichia coli, and some key reaction parameters involved in bioreduction were optimized.As much as 1.1 M of 3,5-BTAP was reduce asymmetrically using whole co-expressing cell in the aqueous system, resulting in a yield of 93.57% and enantiomeric eccess of 99.9%, which were the highest values compared with previous reports.The result indicated that the co-expressed LkCR-GDH has considerable promising potential for the production (R)-BTPE production.And the reaction system is more green, more briefness, more economic.