Cargando…
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...
Autores principales: | , |
---|---|
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 |
_version_ | 1784572914211749888 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8465588 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT wangjie resolutionofhalogenatedmandelicacidsthroughenantiospecificcocrystallizationwithlevetiracetam AT pengyangfeng resolutionofhalogenatedmandelicacidsthroughenantiospecificcocrystallizationwithlevetiracetam |