Department of Molecular Chemistry, Materials and Catalysis, Institute of Condensed Matter and Nanosciences, Université Catholique de Louvain, Place Louis Pasteur, 1 bte L4.01.06, BE-1348, Louvain-La-Neuve, Belgium.
Angew Chem Int Ed Engl. 2020 Jul 6;59(28):11303-11306. doi: 10.1002/anie.202002464. Epub 2020 Apr 6.
Processes leading to enantiomerically pure compounds are of utmost importance, in particular for the pharmaceutical industry. Starting from a racemic mixture, crystallization-induced diastereomeric transformation allows in theory for 100 % transformation of the desired enantiomer. However, this method has the inherent limiting requirement for the organic compound to form a salt. Herein, this limitation is lifted by introducing cocrystallization in the context of thermodynamic deracemization, with the process applied to a model chiral fungicide. We report a new general single thermodynamic deracemization process based on cocrystallization for the deracemization of (R,S)-4,4-dimethyl-1-(4-fluorophenyl)-2-(1H-1,2,4-triazol-1-yl)pentan-3-one. This study demonstrates the feasibility of this novel approach and paves the way to further development of such processes.
对于制药行业来说，能够得到光学纯的化合物是非常重要的，特别是对于那些手性药物。从外消旋混合物开始，晶型诱导的非对映异构体转化理论上可以将所需的对映异构体 100%转化。然而，这种方法有一个固有的限制条件，就是所研究的有机化合物需要形成盐。在这里，通过在热动力学外消旋化的背景下引入共结晶，克服了这一限制，该方法应用于一个手性农药模型。我们报道了一个新的基于共结晶的通用的单热力学外消旋化过程，用于（R，S）-4，4-二甲基-1-（4-氟苯基）-2-（1H-1,2,4-三唑-1-基）戊烷-3-酮的外消旋化。本研究证明了这种新方法的可行性，为进一步发展这类方法铺平了道路。
