Diversity-oriented synthesis of glycomimetics
Glycomimetics are structural mimics of naturally occurring carbohydrates and represent important therapeutic leads in several disease treatments. However, the structural and stereochemical complexity inherent to glycomimetics often challenges medicinal chemistry efforts and is incompatible with dive...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814271/ https://www.ncbi.nlm.nih.gov/pubmed/36697548 http://dx.doi.org/10.1038/s42004-021-00520-3 |
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author | Meanwell, Michael Fehr, Gaelen Ren, Weiwu Adluri, Bharanishashank Rose, Victoria Lehmann, Johannes Silverman, Steven M. Rowshanpour, Rozhin Adamson, Christopher Bergeron-Brlek, Milan Foy, Hayden Challa, Venugopal Rao Campeau, Louis-Charles Dudding, Travis Britton, Robert |
author_facet | Meanwell, Michael Fehr, Gaelen Ren, Weiwu Adluri, Bharanishashank Rose, Victoria Lehmann, Johannes Silverman, Steven M. Rowshanpour, Rozhin Adamson, Christopher Bergeron-Brlek, Milan Foy, Hayden Challa, Venugopal Rao Campeau, Louis-Charles Dudding, Travis Britton, Robert |
author_sort | Meanwell, Michael |
collection | PubMed |
description | Glycomimetics are structural mimics of naturally occurring carbohydrates and represent important therapeutic leads in several disease treatments. However, the structural and stereochemical complexity inherent to glycomimetics often challenges medicinal chemistry efforts and is incompatible with diversity-oriented synthesis approaches. Here, we describe a one-pot proline-catalyzed aldehyde α-functionalization/aldol reaction that produces an array of stereochemically well-defined glycomimetic building blocks containing fluoro, chloro, bromo, trifluoromethylthio and azodicarboxylate functional groups. Using density functional theory calculations, we demonstrate both steric and electrostatic interactions play key diastereodiscriminating roles in the dynamic kinetic resolution. The utility of this simple process for generating large and diverse libraries of glycomimetics is demonstrated in the rapid production of iminosugars, nucleoside analogues, carbasugars and carbohydrates from common intermediates. |
format | Online Article Text |
id | pubmed-9814271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98142712023-01-10 Diversity-oriented synthesis of glycomimetics Meanwell, Michael Fehr, Gaelen Ren, Weiwu Adluri, Bharanishashank Rose, Victoria Lehmann, Johannes Silverman, Steven M. Rowshanpour, Rozhin Adamson, Christopher Bergeron-Brlek, Milan Foy, Hayden Challa, Venugopal Rao Campeau, Louis-Charles Dudding, Travis Britton, Robert Commun Chem Article Glycomimetics are structural mimics of naturally occurring carbohydrates and represent important therapeutic leads in several disease treatments. However, the structural and stereochemical complexity inherent to glycomimetics often challenges medicinal chemistry efforts and is incompatible with diversity-oriented synthesis approaches. Here, we describe a one-pot proline-catalyzed aldehyde α-functionalization/aldol reaction that produces an array of stereochemically well-defined glycomimetic building blocks containing fluoro, chloro, bromo, trifluoromethylthio and azodicarboxylate functional groups. Using density functional theory calculations, we demonstrate both steric and electrostatic interactions play key diastereodiscriminating roles in the dynamic kinetic resolution. The utility of this simple process for generating large and diverse libraries of glycomimetics is demonstrated in the rapid production of iminosugars, nucleoside analogues, carbasugars and carbohydrates from common intermediates. Nature Publishing Group UK 2021-06-24 /pmc/articles/PMC9814271/ /pubmed/36697548 http://dx.doi.org/10.1038/s42004-021-00520-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Meanwell, Michael Fehr, Gaelen Ren, Weiwu Adluri, Bharanishashank Rose, Victoria Lehmann, Johannes Silverman, Steven M. Rowshanpour, Rozhin Adamson, Christopher Bergeron-Brlek, Milan Foy, Hayden Challa, Venugopal Rao Campeau, Louis-Charles Dudding, Travis Britton, Robert Diversity-oriented synthesis of glycomimetics |
title | Diversity-oriented synthesis of glycomimetics |
title_full | Diversity-oriented synthesis of glycomimetics |
title_fullStr | Diversity-oriented synthesis of glycomimetics |
title_full_unstemmed | Diversity-oriented synthesis of glycomimetics |
title_short | Diversity-oriented synthesis of glycomimetics |
title_sort | diversity-oriented synthesis of glycomimetics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814271/ https://www.ncbi.nlm.nih.gov/pubmed/36697548 http://dx.doi.org/10.1038/s42004-021-00520-3 |
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