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Efficient Synthesis of (S)-1-Boc-3-aminopiperidine in a Continuous Flow System Using ω-Transaminase-Immobilized Amino-Ethylenediamine-Modified Epoxide Supports
Organic Process Research & Development ( IF 3.4 ) Pub Date : 2022-04-15 , DOI: 10.1021/acs.oprd.1c00217
Xiangxiang Wang, Youyu Xie, Zhicai Wang, Ke Zhang, Hualei Wang, Dongzhi Wei

We developed a continuous flow system using ω-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 ω-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 ω-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 g·L–1·day–1, indicating outstanding reaction efficiency. This efficient continuous bioprocess has potential for large-scale production of (S)-1-Boc-3-aminopiperidine.

中文翻译:

使用 ω-转氨酶固定的氨基-乙二胺修饰的环氧化物载体在连续流动系统中高效合成 (S)-1-Boc-3-氨基哌啶

我们开发了一种连续流动系统,使用共价固定在乙二胺 (EDA) 改性环氧树脂上的 ω-转氨酶来合成 ( S )-1-Boc-3-氨基哌啶,这是几种新型抑制剂的关键中间体。引入第二个官能团(-NH 3 +)以快速吸附ω-转氨酶,通过多点共价连接到改性树脂上进一步硬化,具有高结合效率(> 95%)和活性恢复(75%)。得到的固定化 ω-转氨酶在 15 次重复使用循环后稳定,具有 90% 的残留活性。我们合成了(S)-1-Boc-3-aminopiperidine 使用这种连续流动系统,在停留 10 分钟内获得 95% 的转化率。系统连续运行24 h,时空产率为930.73 g·L -1 ·day -1,反应效率高。这种高效的连续生物工艺具有大规模生产( S )-1-Boc-3-氨基哌啶的潜力。
更新日期:2022-04-15
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