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Resolution of Halogenated Mandelic Acids through Enantiospecific Co-Crystallization with Levetiracetam

The resolution of halogenated mandelic acids using levetiracetam (LEV) as a resolving agent via forming enantiospecific co-crystal was presented. Five halogenated mandelic acids, 2-chloromandelic acid (2-ClMA), 3-chloromandelic acid (3-ClMA), 4-chloromandelic acid (4-ClMA), 4-bromomandelic acid (4-B...

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Autores principales: Wang, Jie, Peng, Yangfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465588/
https://www.ncbi.nlm.nih.gov/pubmed/34577007
http://dx.doi.org/10.3390/molecules26185536
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author Wang, Jie
Peng, Yangfeng
author_facet Wang, Jie
Peng, Yangfeng
author_sort Wang, Jie
collection PubMed
description The resolution of halogenated mandelic acids using levetiracetam (LEV) as a resolving agent via forming enantiospecific co-crystal was presented. Five halogenated mandelic acids, 2-chloromandelic acid (2-ClMA), 3-chloromandelic acid (3-ClMA), 4-chloromandelic acid (4-ClMA), 4-bromomandelic acid (4-BrMA), and 4-fluoromandelic acid (4-FMA), were selected as racemic compounds. The effects of the equilibrium time, molar ratio of the resolving agent to racemate, amount of solvent, and crystallization temperature on resolution performance were investigated. Under the optimal conditions, the resolution efficiency reached up to 94% and the enantiomeric excess (%e.e.) of (R)-3-chloromandelic acid was 63%e.e. All five halogenated mandelic acids of interest in this study can be successfully separated by LEV via forming enantiospecific co-crystal, but the resolution performance is significantly different. The results showed that LEV selectively co-crystallized with S enantiomers of 2-ClMA, 3-ClMA, 4-ClMA, and 4-BrMA, while it co-crystallized with R enantiomers of 4-FMA. This indicates that the position and type of substituents of racemic compounds not only affect the co-crystal configuration, but also greatly affect the efficiency of co-crystal resolution.
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spelling pubmed-84655882021-09-27 Resolution of Halogenated Mandelic Acids through Enantiospecific Co-Crystallization with Levetiracetam Wang, Jie Peng, Yangfeng Molecules Article The resolution of halogenated mandelic acids using levetiracetam (LEV) as a resolving agent via forming enantiospecific co-crystal was presented. Five halogenated mandelic acids, 2-chloromandelic acid (2-ClMA), 3-chloromandelic acid (3-ClMA), 4-chloromandelic acid (4-ClMA), 4-bromomandelic acid (4-BrMA), and 4-fluoromandelic acid (4-FMA), were selected as racemic compounds. The effects of the equilibrium time, molar ratio of the resolving agent to racemate, amount of solvent, and crystallization temperature on resolution performance were investigated. Under the optimal conditions, the resolution efficiency reached up to 94% and the enantiomeric excess (%e.e.) of (R)-3-chloromandelic acid was 63%e.e. All five halogenated mandelic acids of interest in this study can be successfully separated by LEV via forming enantiospecific co-crystal, but the resolution performance is significantly different. The results showed that LEV selectively co-crystallized with S enantiomers of 2-ClMA, 3-ClMA, 4-ClMA, and 4-BrMA, while it co-crystallized with R enantiomers of 4-FMA. This indicates that the position and type of substituents of racemic compounds not only affect the co-crystal configuration, but also greatly affect the efficiency of co-crystal resolution. MDPI 2021-09-12 /pmc/articles/PMC8465588/ /pubmed/34577007 http://dx.doi.org/10.3390/molecules26185536 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Jie
Peng, Yangfeng
Resolution of Halogenated Mandelic Acids through Enantiospecific Co-Crystallization with Levetiracetam
title Resolution of Halogenated Mandelic Acids through Enantiospecific Co-Crystallization with Levetiracetam
title_full Resolution of Halogenated Mandelic Acids through Enantiospecific Co-Crystallization with Levetiracetam
title_fullStr Resolution of Halogenated Mandelic Acids through Enantiospecific Co-Crystallization with Levetiracetam
title_full_unstemmed Resolution of Halogenated Mandelic Acids through Enantiospecific Co-Crystallization with Levetiracetam
title_short Resolution of Halogenated Mandelic Acids through Enantiospecific Co-Crystallization with Levetiracetam
title_sort resolution of halogenated mandelic acids through enantiospecific co-crystallization with levetiracetam
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465588/
https://www.ncbi.nlm.nih.gov/pubmed/34577007
http://dx.doi.org/10.3390/molecules26185536
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