固体溶液行为的溶剂触发分解使RS-phenprocoumon的直接抗选择性结晶成为可能
Yihua Jiang1, Sokhna Souare2, Koen Robeyns1
1Institute of Condensed Matter and Nanosciences, Université catholique de Louvain, 1348 Louvain-La-Neuve, Belgium. tom.leyssens@uclouvain.be.
概括
溶剂的选择是phenprocoumon-quinidine的奇拉性溶解的关键. 使用乙会产生双乙溶酸盐,使S-phenprocoumon在一个步骤中以高纯度自发的选择性结晶成为可能.
科学领域:
- 基质化学 基质化学 基质化学
- 结晶科学是结晶的科学.
- 制药分析 制药分析
背景情况:
- 种族化合物的基质分辨率对于药物开发至关重要.
- 芬普罗库蒙是一种需要分离的种族药物.
- 之前用于phenprocoumon解决的方法是无效的.
研究的目的:
- 调查溶剂选择在RS-phenprocoumon的奇拉分辨率中的作用.
- 开发一种有效的方法,用于S-phenprocoumon的enantioselective结晶.
主要方法:
- 使用各种溶剂的RS-phenprocoumon-quinidine的奇拉分辨率.
- 对结晶形成和固体溶液抑制的分析.
- 使用分析技术确定反体过量.
主要成果:
- 溶剂的选择极大地影响了性分辨率的效率.
- 形成双酸盐溶剂有效抑制了固体溶液的形成.
- 自发的S-phenprocoumon的enantioselective结晶实现了高达92%的反体过剩.
- 一个单一的分辨率步骤产生了高的enantiopurity.
结论:
- 双酸盐溶盐的形成是有效的奇拉分辨率的关键策略.
- 这种方法提供了一种简化和有效的途径,以获得S-phenprocoumon.
- 这些发现为工业规模生产纯制药品提供了一种新方法.
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