Use of Lipase Catalytic Resolution in the Preparation of Ethyl (2S,5R)-5-((Benzyloxy)amino)piperidine-2-carboxylate, a Key Intermediate of the β-Lactamase Inhibitor Avibactam

作者：Wang, Tao; Du, Liang-Dong; Wan, Ding-jian; Li, Xiang; Chen, Xin-Zhi^*; Wu, Guo-Feng^*

来源：Organic Process Research & Development, 2018, 22(12): 1738-1744.

DOI：10.1021/acs.oprd.8b00173

• avibactam
• Lipozyme CALB
• lipase-catalyzed resolution
• chiral isomers

Here we describe an efficient and cost-effective chemoenzymatic synthesis of the beta-lactamase inhibitor avibactam starting from commercially available ethyl 5-hydroxypicolinate hydrochloride. Avibactam was synthesized in 10 steps with an overall yield of 23.9%. The synthetic route features a novel lipase-catalyzed resolution step during the preparation of (2S,5S)ethyl 5-hydroxypiperidine-2-carboxylate, a valuable precursor of the key intermediate ethyl (2S,SR)-5-((benzyloxy)amino)piperidine-2-carboxylate. Our synthetic route was used to produce 400 g of avibactam sodium salt.

• 出版日期2018-12
• 单位浙江大学