开发一种可持续的"一子"工艺,通过对铁的酶选择性催化,生产埃索梅普拉
Shigenobu Nishiguchi1, Junpei Sukegawa1, Takuma Onai1
1API Process Research Department, API Business Division, Towa Pharmaceutical Co., Ltd., Amagasaki Research Incubation Center 3F, 7-1-3 Doi-cho, Amagasaki, Hyogo 660-0083, Japan.
Chemical & pharmaceutical bulletin
|November 24, 2025
概括
这项研究提出了一种可持续的方法,使用廉价的铁催化剂生产高纯度的埃索梅普拉. 开发的非对称硫化反应实现了卓越的反选择性,为高效的制药制造铺平了道路.
科学领域:
- 绿色化学 绿色化学
- 不对称的催化剂.
- 制药合成 制药合成
背景情况:
- 可持续的有机合成需要具有成本效益和无毒的催化剂.
- 同质的性铁 (Fe) 催化剂显示出希望,但与复杂分子合成作斗争.
- 现有的埃索梅普拉生产方法需要优化,以实现大规模,高纯度的输出.
研究的目的:
- 开发一种可扩展的不对称的硫氧化反应,用于埃索梅普拉的生产.
- 建立高纯度活性药物成分 (API) 的高效制造工艺.
- 为了研究酶选择性铁催化氧化的催化机制.
主要方法:
- 从铁盐,奇拉的希夫联体和碳酸盐中在现场生成一种催化系统.
- 使用过氧化作为氧化剂进行不对称的硫化氧化.
- 盐埃索梅普拉转化为盐用于净化.
主要成果:
- 在试点工厂规模上成功进行了对象不对称的硫氧化,以生产埃索梅普拉.
- 实现了高纯度的API,杂质低于0.05%.
- 证明了依赖基质空间配置的反选择性.
结论:
- 开发的铁催化非对称硫氧化是一种可行的方法,用于可持续的埃索梅普拉制造.
- 该过程产生了具有受控杂质的高纯度API.
- 提出了一种催化机制,涉及碳酸激活过氧化和铁氧化剂的形成.
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