通过相转移催化方法对硫胺胺的S-化
Andrew T Champlin1, Na Yeon Kwon1, Jonathan A Ellman1
1Department of Chemistry, Yale University, 225 Prospect St., New Haven, CT 06520, USA.
Angewandte Chemie (International ed. in English)
|July 26, 2024
概括
使用相转移催化剂 (PTC) 和一种新型的保护组合成了化硫化合物. 这种方法可以在低温下对N-acylsulfenamides进行抗选择性化,从而产生有价值的硫胺中间体.
科学领域:
- 有机化学 有机化学
- 不对称的合成方法
- 催化剂是一种催化剂.
背景情况:
- 硫胺在药物发现中是重要的药解剂.
- 合成性硫化合物的高效和酶选择性方法非常受欢迎.
- 以前的获取性硫胺的方法往往涉及复杂的程序或有限的范围.
研究的目的:
- 开发一种N-酸硫胺的通用和酶选择性相移催化 (PTC) 化.
- 建立一种强大的方法来合成奇拉硫胺和它们相应的硫胺衍生物.
- 为了证明开发的方法在合成已知的制药中间体的实用性.
主要方法:
- 使用 cinchona 类化合物衍生的催化剂进行选酶相转移催化.
- 在低温 (-40°C) 的双相水态条件下化N-乙硫胺.
- 由此产生的硫胺氧化为硫胺,然后进行减弱裂变.
主要成果:
- 新形成的性硫中心的高反体比率 (高达97.5:2.5) 得到了实现.
- 该方法证明了广泛的范围和与各种硫胺基的优良功能组兼容性.
- 伪反体催化剂成功地被设计为访问两个反体.
- 一个I期临床候选药物的合成,阿图韦西克利布 (Atuveciclib),以高效率实现.
结论:
- 已经开发出一种多功能且高效的PTC介导的N-酸硫胺的酶选择性化.
- 这种方法可以获得具有高立体控制的有价值的合硫胺构建块.
- 这种方法为复杂分子的不对称合成提供了一个实用的途径,包括药物候选物.
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