Simultaneous chiral resolution of two racemic compounds by preferential cocrystallization

Fuli Zhou; Oleksii Shemchuk; Maxime D. Charpentier; Chloé Matheys; Laurent Collard; Joop H. ter Horst; Tom Leyssens

doi:https://chemrxiv.org/engage/chemrxiv/article-details/60c759c6842e65bb48db4a9a

Simultaneous chiral resolution of two racemic compounds by preferential cocrystallization

Fuli Zhou, Oleksii Shemchuk, Maxime D. Charpentier, Chloé Matheys, Laurent Collard, Joop H. ter Horst, Tom Leyssens^*

^*Corresponding author for this work

Strathclyde Institute Of Pharmacy And Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

50 Citations (Scopus)

13 Downloads (Pure)

Abstract

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.

Original language	English
Pages (from-to)	20264-20268
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	60
Issue number	37
Early online date	6 Aug 2021
DOIs	https://doi.org/https://chemrxiv.org/engage/chemrxiv/article-details/60c759c6842e65bb48db4a9a https://doi.org/10.1002/anie.202107804
Publication status	Published - 6 Sept 2021

Funding

F.Z. would like to thank the China Scholarship Council (CSC) for financial support. The “FSR Incoming Post‐doctoral Fellowship” is acknowledged for financial support of OS. This work was financed by PDR T.0149.19. M.D.C. and J.H.tH received funding as part of the CORE project (October 2016‐September 2020) from the European Union Horizon 2020 Research and Innovation Program under the Marie Sklodowska‐Curie grant arrangement No 722456 CORE ITN.

Keywords

chiral resolution
cocrystals
conglomerate
preferential crystallization
simultaneous resolution

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Zhou-etal-ACIE-2021-Simultaneous-chiral-resolution-of-two-racemic-compoundsAccepted author manuscript, 3.7 MB

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Zhou, F., Shemchuk, O., Charpentier, M. D., Matheys, C., Collard, L., ter Horst, J. H., & Leyssens, T. (2021). Simultaneous chiral resolution of two racemic compounds by preferential cocrystallization. Angewandte Chemie - International Edition, 60(37), 20264-20268. https://doi.org/https://chemrxiv.org/engage/chemrxiv/article-details/60c759c6842e65bb48db4a9a, https://doi.org/10.1002/anie.202107804

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title = "Simultaneous chiral resolution of two racemic compounds by preferential cocrystallization",

abstract = "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.",

keywords = "chiral resolution, cocrystals, conglomerate, preferential crystallization, simultaneous resolution",

author = "Fuli Zhou and Oleksii Shemchuk and Charpentier, \{Maxime D.\} and Chlo{\'e} Matheys and Laurent Collard and \{ter Horst\}, \{Joop H.\} and Tom Leyssens",

note = "A previous version of this manuscript has been deposited on a preprint server (https://doi.org/10.26434/chemrxiv.14730537.v1).",

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Zhou, F, Shemchuk, O, Charpentier, MD, Matheys, C, Collard, L, ter Horst, JH & Leyssens, T 2021, 'Simultaneous chiral resolution of two racemic compounds by preferential cocrystallization', Angewandte Chemie - International Edition, vol. 60, no. 37, pp. 20264-20268. https://doi.org/https://chemrxiv.org/engage/chemrxiv/article-details/60c759c6842e65bb48db4a9a, https://doi.org/10.1002/anie.202107804

TY - JOUR

T1 - Simultaneous chiral resolution of two racemic compounds by preferential cocrystallization

AU - Zhou, Fuli

AU - Shemchuk, Oleksii

AU - Charpentier, Maxime D.

AU - Matheys, Chloé

AU - Collard, Laurent

AU - ter Horst, Joop H.

AU - Leyssens, Tom

N1 - A previous version of this manuscript has been deposited on a preprint server (https://doi.org/10.26434/chemrxiv.14730537.v1).

PY - 2021/9/6

Y1 - 2021/9/6

N2 - 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.

AB - 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.

KW - chiral resolution

KW - cocrystals

KW - conglomerate

KW - preferential crystallization

KW - simultaneous resolution

UR - https://www.scopus.com/pages/publications/85111921237

U2 - https://chemrxiv.org/engage/chemrxiv/article-details/60c759c6842e65bb48db4a9a

DO - https://chemrxiv.org/engage/chemrxiv/article-details/60c759c6842e65bb48db4a9a

M3 - Article

AN - SCOPUS:85111921237

SN - 1433-7851

VL - 60

SP - 20264

EP - 20268

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 37

ER -

Simultaneous chiral resolution of two racemic compounds by preferential cocrystallization

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CORE - Continuous Resolution and Deracemization of Chiral Compounds by Crystallization MSCA ETN

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Simultaneous chiral resolution of two racemic compounds by preferential cocrystallization

Abstract

Funding

Keywords

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CORE - Continuous Resolution and Deracemization of Chiral Compounds by Crystallization MSCA ETN

Cite this