Asymmetric synthesis of an enantiomerically pure rivastigmine intermediate using ketoreductase |
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Authors: | Madhuresh K Sethi Somashekar R Bhandya Nagaraj Maddur Rohit Shukla Anish Kumar VSN Jayalakshmi Mittapalli |
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Institution: | R&D, Mylan Laboratories Ltd, Plot No. 31, 32, 33 and 34 A ANRICH Industrial Estate, Bollaram (Village), Jinnaram (Mandal), Medak (Dt) 502325, Andhra Pradesh, India |
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Abstract: | A novel chemo-enzymatic synthesis of (S)-rivastigmine using ketoreductases with NADH/NADPH as the proton donor has been demonstrated. An exclusive enzymatic process has been developed by exploring the possible ketoreductases by screening to identify enzymes useful for the preparation of the (S)-isomer intermediate, and scaling up of the enzymatic process for the production of an adequate, enantiomerically pure precursor of rivastigmine and for the total synthesis of (S)-rivastigmine. |
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