Efficient Synthesis of (S)-1-Boc-3-aminopiperidine in a Continuous Flow System Using ?-Transaminase-Immobilized Amino-Ethylenediamine-Modified Epoxide Supports

被引：6

作者：

Wang, Xiangxiang ^{[1
]}

Xie, Youyu ^{[1
]}

Wang, Zhicai ^{[1
]}

Zhang, Ke ^{[1
]}

Wang, Hualei ^{[1
]}

Wei, Dongzhi ^{[1
]}

机构：

[1] East China Univ Sci & Technol, New World Inst Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2022年

基金：

中国国家自然科学基金;

关键词：

enzyme immobilization; bifunctional supports; transaminases; biocatalysis; flow chemistry; ASYMMETRIC-SYNTHESIS; CHIRAL AMINES; ARYLATION;

D O I：

10.1021/acs.oprd.1c00217

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

We developed a continuous flow system using omega-transaminase covalently immobilized on an epoxy resin modified with ethylenediamine (EDA) to synthesize (S)-1-Boc-3-aminopiperidine, which is a key intermediate for several novel inhibitors. A second functional group (-NH3+) was introduced to rapidly adsorb omega-transaminase, which was further rigidified by multipoint covalent attachment to the modified resin with high binding efficiency (> 95%) and activity recovery (75%). The resulting immobilized omega-transaminase was stable with 90% residual activity after 15 reuse cycles. We synthesized (S)-1-Boc-3-aminopiperidine using this continuous flow system, and 95% conversion was obtained within 10 min of residence. The system was continuously operated for 24 h and achieved a space-time yield of 930.73 gmiddotL(-1)middotday(-1), indicating outstanding reaction efficiency. This efficient continuous bioprocess has potential for large-scale production of (S)-1-Boc-3-aminopiperidine.

引用

页码：1351 / 1359

页数：9