催化脱用于可持续的溶液和固相合成
Maria Camila Aguilera1, Steven W M Crossley1, Renee J Sifri1
1Process Research & Development, MRL, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
一种新的催化方法使得固相合成 (SPPS) 的有效的基/基去保护成为可能. 这种具有成本效益的方法可以提高树脂上的兼容性,促进类药物开发.
科学领域:
- 有机化学 有机化学
- 合成化学 合成化学
- 药用化学 医学化学
背景情况:
- 传统的基/基脱保护通常依赖于昂贵的基催化剂.
- 现有的基础金属替代品与在树脂上的固相合成 (SPPS) 的兼容性有限.
研究的目的:
- 开发一种成本效益高的,单阶段催化方法,用于基/基去保护.
- 建立一个与固相合成 (SPPS) 兼容的协议,包括在树脂上的应用.
主要方法:
- 采用了采用空气稳定的Ni (PPh) 预催化剂和NH (BH) 减少剂的两组系统.
- 在惰性条件下,在SPPS兼容的溶剂中快速进行反应.
主要成果:
- 催化协议实现了有效和化学选择性去除溶液中的和受保护的氨基酸,小分子和的保护.
- 该方法已成功扩展到在树脂上的去保护,证明了其在SPPS中的实用性.
结论:
- 这种单步催化脱保护方法为SPPS提供了可行的,经济高效的替代方案,而不是基于的系统.
- 已证明的在树脂上的兼容性为推进合成策略提供了重大前景.
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