Separation of Stereoisomeric Mixtures of Nafronyl as a Representative of Compounds Possessing Two Stereogenic Centers By Coupling Crystallization, Diastereoisomeric Conversion and Chromatography

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• 作者：Dawid Kiwala ; Maksymilian Olbrycht ; Maciej Balawejder ; Wojciech Piątkowski ; Andreas Seidel-Morgenstern ; Dorota Antos
• 刊名：Organic Process Research & Development
• 出版年：2016
• 出版时间：March 18, 2016
• 年：2016
• 卷：20
• 期：3
• 页码：615-625
• 全文大小：486K
• ISSN：1520-586X

文摘

A procedure for the isolation of the most biologically active component of a stereoisomeric mixture of nafronyl-2-(diethylamino)ethyl 3-(naphthalen-1-yl)-2-((tetrahydrofuran-2-yl)methyl)propanoate has been proposed. The molecule of nafronyl is a representative of compounds possessing two stereogenic centers, which may be produced in the form of a quaternary mixture that contains two pairs of racemates being diastereoisomers of one another. The components of such stereoisomeric mixtures usually differ in pharmacological activity; therefore, there is an interest in developing efficient methods for their resolution. The method suggested in this study comprised two sequential separation processes, including multistage cross-current crystallization and chiral chromatography. Crystallization was employed to enrich the raw material mixture with the target racemate, which contained the stereoisomer exhibiting the highest biological activity. To intensify the process, the mother liquors depleted with the target racemate were subjected to fast base-catalyzed diastereoisomeric conversion in the melt, which provided equimolar mixtures of all four stereoisomers. The coupling of cross-current crystallization and diastereoisomeric conversion could improve yield of crystallization from 29% up to 84%. The purified racemate was further processed by chromatography to isolate finally the most active stereoisomer with 99% purity and total yield of 84%, at a relatively high throughput.