Institute of Condensed Matter and Nanosciences, Place Louis Pasteur, 1 bte L4.01.06, 1348, Louvain-La-Neuve, Belgium.
EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation (CMAC), Strathclyde Institute of Pharmacy and Biomedical Sciences, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, G1 1RD, UK.
Angew Chem Int Ed Engl. 2021 Sep 6;60(37):20264-20268. doi: 10.1002/anie.202107804. Epub 2021 Aug 6.
We tap into an unexplored area of preferential crystallization, being the first to develop simultaneous chiral resolution of two racemic compounds by preferential cocrystallization. We highlight how the two racemic compounds RS-mandelic acid (MAN) and RS-etiracetam (ETI) can be combined together as enantiospecific R-MAN⋅R-ETI and S-MAN⋅S-ETI cocrystals forming a stable conglomerate system and subsequently develop a cyclic preferential crystallization allowing to simultaneous resolve both compounds. The developed process leads to excellent enantiopurity both for etiracetam (ee>98 %) and mandelic acid (ee≈95 %) enantiomers.
我们探索了一个未曾涉足的优先结晶领域，首次开发出通过优先共结晶同时对两种外消旋化合物进行手性拆分的方法。我们强调了如何将两种外消旋化合物 RS-扁桃酸（MAN）和 RS-依托咪酯（ETI）组合在一起，形成手性特异性 R-MAN⋅R-ETI 和 S-MAN⋅S-ETI 共晶，形成稳定的附聚体系，随后开发出循环优先结晶，允许同时拆分这两种化合物。所开发的工艺可使依托咪酯（ee＞98％）和扁桃酸（ee≈95％）对映体都具有出色的对映体纯度。
