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| A highly efficient way to recycle inactive stereoisomers of Bedaquiline into two previous intermediates via base-catalyzed Csp3-Csp3 bond cleavage |
| De-Long Kong, Ye Huang, Lai-Yang Ren, Wen-Hua Feng |
| Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China |
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Abstract Bedaquiline is a new medicine for pulmonary multi-drug resistant tuberculosis (MDR-TB), which is a pure enantiomer with two chiral centers. The current industrial preparation process requires the separation of active Bedaquiline from a mixture of four isomers. Obviously, direct dispose of the other three undesired stereoisomers will cause significant waste and increase the unnecessary cost of production. Here, we developed an efficient, facile and scalable process for recycling the inactive stereoisomers of Bedaquiline. All these inactive stereoisomers could be recycled by their conversion to two important intermediates in the Bedaquiline synthesis via a base-catalyzed Csp3-Csp3 bond cleavage of a benzyl alcohol intermediate. And the precise conditions and mechanism of the base-catalyzed cleavage reaction were discussed.
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Received: 28 January 2015
Published: 18 April 2015
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| Fund: This research was financially supported by the National Science and Technology Major Project of China (No. 521042). |
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Corresponding Authors:
Ye Huang, Wen-Hua Feng
E-mail: huangye@imm.ac.cn;fwh@imm.ac.cn
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