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Chiral Amplification through the Interplay of Racemizing Conditions and Asymmetric Crystal Growth
[Image: see text] Amplification of enantiomeric excesses (ee) is routinely observed during chiral crystallization of conglomerate crystals for which the enantiomers undergo racemization in solution. Although routes comprising a combination of crystal growth and dissolution are frequently used to obt...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837840/ https://www.ncbi.nlm.nih.gov/pubmed/36534614 http://dx.doi.org/10.1021/jacs.2c10584 |
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author | van Dongen, Sjoerd W. Ahlal, Imane Leeman, Michel Kaptein, Bernard Kellogg, Richard M. Baglai, Iaroslav Noorduin, Willem L. |
author_facet | van Dongen, Sjoerd W. Ahlal, Imane Leeman, Michel Kaptein, Bernard Kellogg, Richard M. Baglai, Iaroslav Noorduin, Willem L. |
author_sort | van Dongen, Sjoerd W. |
collection | PubMed |
description | [Image: see text] Amplification of enantiomeric excesses (ee) is routinely observed during chiral crystallization of conglomerate crystals for which the enantiomers undergo racemization in solution. Although routes comprising a combination of crystal growth and dissolution are frequently used to obtain enantiopure molecules, crystal growth by itself has rather been considered as a source of enantiomeric erosion and discounted as a potential source of enantiomeric amplification. Counterintuitively, we here demonstrate striking enantiomeric amplification during crystal growth for clopidogrel and tert-leucine precursors. Based on a mechanistic framework, we identify that the interplay between racemization and crystal growth rates elicits this surprising effect. The asymmetric amplification of the solid-phase ee can be enhanced by increasing the mass of grown material relative to the product such that small amounts of seeds of only 60% ee already result in virtually exclusive growth of the majority phase. These results impact our understanding of asymmetric amplification mechanisms during crystallization and offer a tangible basis for practical production of enantiopure molecules. |
format | Online Article Text |
id | pubmed-9837840 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-98378402023-01-14 Chiral Amplification through the Interplay of Racemizing Conditions and Asymmetric Crystal Growth van Dongen, Sjoerd W. Ahlal, Imane Leeman, Michel Kaptein, Bernard Kellogg, Richard M. Baglai, Iaroslav Noorduin, Willem L. J Am Chem Soc [Image: see text] Amplification of enantiomeric excesses (ee) is routinely observed during chiral crystallization of conglomerate crystals for which the enantiomers undergo racemization in solution. Although routes comprising a combination of crystal growth and dissolution are frequently used to obtain enantiopure molecules, crystal growth by itself has rather been considered as a source of enantiomeric erosion and discounted as a potential source of enantiomeric amplification. Counterintuitively, we here demonstrate striking enantiomeric amplification during crystal growth for clopidogrel and tert-leucine precursors. Based on a mechanistic framework, we identify that the interplay between racemization and crystal growth rates elicits this surprising effect. The asymmetric amplification of the solid-phase ee can be enhanced by increasing the mass of grown material relative to the product such that small amounts of seeds of only 60% ee already result in virtually exclusive growth of the majority phase. These results impact our understanding of asymmetric amplification mechanisms during crystallization and offer a tangible basis for practical production of enantiopure molecules. American Chemical Society 2022-12-19 /pmc/articles/PMC9837840/ /pubmed/36534614 http://dx.doi.org/10.1021/jacs.2c10584 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | van Dongen, Sjoerd W. Ahlal, Imane Leeman, Michel Kaptein, Bernard Kellogg, Richard M. Baglai, Iaroslav Noorduin, Willem L. Chiral Amplification through the Interplay of Racemizing Conditions and Asymmetric Crystal Growth |
title | Chiral Amplification
through the Interplay of Racemizing
Conditions and Asymmetric Crystal Growth |
title_full | Chiral Amplification
through the Interplay of Racemizing
Conditions and Asymmetric Crystal Growth |
title_fullStr | Chiral Amplification
through the Interplay of Racemizing
Conditions and Asymmetric Crystal Growth |
title_full_unstemmed | Chiral Amplification
through the Interplay of Racemizing
Conditions and Asymmetric Crystal Growth |
title_short | Chiral Amplification
through the Interplay of Racemizing
Conditions and Asymmetric Crystal Growth |
title_sort | chiral amplification
through the interplay of racemizing
conditions and asymmetric crystal growth |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837840/ https://www.ncbi.nlm.nih.gov/pubmed/36534614 http://dx.doi.org/10.1021/jacs.2c10584 |
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