在微波辐射下使用 ω-转氨酶和胆化物作为活性制药成分中间体的奇拉尔胺的立体选择生物机械催化级联
Salvatore Romano1,2, Matteo Damian1, Monica Nardi2
1Van 't Hoff Institute for Molecular Sciences, HIMS-Biocat, University of Amsterdam, Amsterdam, The Netherlands.
ChemSusChem
|March 15, 2026
概括
这项研究引入了一种绿色的两步方法,用于合成使用生物催化转胺和胆化物介导的化物化物化物化物化物的化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化物化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化化.
科学领域:
- 有机化学 有机化学
- 生物催化剂是一种生物催化剂.
- 可持续化学 可持续化学
背景情况:
- 胺基键的形成对于活性药物成分 (API) 合成至关重要.
- 目前的方法通常涉及恶劣的条件或有毒试剂.
- 开发更绿色,更高效的合成路径对于制药制造至关重要.
研究的目的:
- 开发一种新的生物器官催化级联,用于化胺合成.
- 为了将立体选择性转胺与胆化物介导的直接化结合起来.
- 为制造制药中间体建立一个可持续和高效的生产途径.
主要方法:
- 在纯有机溶剂 (MTBE) 中使用 ω-转氨酶 (ω-TAs) 的优化立体选择性转氨基化.
- 在无溶剂的微波条件下,通过胆化物 (ChCl) 介导的集成直接化.
- 使用溶剂蒸发来去除副产品并提高化效率.
主要成果:
- 实现了Racecadotril和AVR-48.8的关键中间体的完全转换和> 99%的反体过量.
- 证明了 ChCl 介导的化物对各种碳酸的高效率 (60% - 86%的产量).
- 验证了溶剂蒸发的必要性,以提高化产量.
结论:
- 开发的综合方法提供了一种绿色,高效和可扩展的途径,用于合成性胺基.
- 这种方法提供了高光学纯度的构建模块,促进了可持续的制药制造.
- 生物器官催化级联代表了胺键形成策略的重大进步.
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