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Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline
Bedaquiline is a crucial medicine in the global fight against tuberculosis, yet its high price places it out of reach for many patients. Herein, we describe improvements to the key industrial lithiation‐addition sequence that enable a higher yielding and therefore more economical synthesis of bedaqu...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545417/ https://www.ncbi.nlm.nih.gov/pubmed/35675114 http://dx.doi.org/10.1002/chem.202201311 |
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author | Mear, Sarah Jane Lucas, Tobias Ahlqvist, Grace P. Robey, Juliana M. S. Dietz, Jule‐Philipp Khairnar, Pankaj V. Maity, Sanjay Williams, Corshai L. Snead, David R. Nelson, Ryan C. Opatz, Till Jamison, Timothy F. |
author_facet | Mear, Sarah Jane Lucas, Tobias Ahlqvist, Grace P. Robey, Juliana M. S. Dietz, Jule‐Philipp Khairnar, Pankaj V. Maity, Sanjay Williams, Corshai L. Snead, David R. Nelson, Ryan C. Opatz, Till Jamison, Timothy F. |
author_sort | Mear, Sarah Jane |
collection | PubMed |
description | Bedaquiline is a crucial medicine in the global fight against tuberculosis, yet its high price places it out of reach for many patients. Herein, we describe improvements to the key industrial lithiation‐addition sequence that enable a higher yielding and therefore more economical synthesis of bedaquiline. Prioritization of mechanistic understanding and multi‐lab reproducibility led to optimized reaction conditions that feature an unusual base‐salt pairing and afford a doubling of the yield of racemic bedaquiline. We anticipate that implementation of these improvements on manufacturing scale will be facile, thereby substantially increasing the accessibility of this essential medication. |
format | Online Article Text |
id | pubmed-9545417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95454172022-10-14 Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline Mear, Sarah Jane Lucas, Tobias Ahlqvist, Grace P. Robey, Juliana M. S. Dietz, Jule‐Philipp Khairnar, Pankaj V. Maity, Sanjay Williams, Corshai L. Snead, David R. Nelson, Ryan C. Opatz, Till Jamison, Timothy F. Chemistry Research Articles Bedaquiline is a crucial medicine in the global fight against tuberculosis, yet its high price places it out of reach for many patients. Herein, we describe improvements to the key industrial lithiation‐addition sequence that enable a higher yielding and therefore more economical synthesis of bedaquiline. Prioritization of mechanistic understanding and multi‐lab reproducibility led to optimized reaction conditions that feature an unusual base‐salt pairing and afford a doubling of the yield of racemic bedaquiline. We anticipate that implementation of these improvements on manufacturing scale will be facile, thereby substantially increasing the accessibility of this essential medication. John Wiley and Sons Inc. 2022-07-07 2022-08-22 /pmc/articles/PMC9545417/ /pubmed/35675114 http://dx.doi.org/10.1002/chem.202201311 Text en © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Mear, Sarah Jane Lucas, Tobias Ahlqvist, Grace P. Robey, Juliana M. S. Dietz, Jule‐Philipp Khairnar, Pankaj V. Maity, Sanjay Williams, Corshai L. Snead, David R. Nelson, Ryan C. Opatz, Till Jamison, Timothy F. Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline |
title | Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline
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title_full | Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline
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title_fullStr | Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline
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title_full_unstemmed | Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline
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title_short | Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline
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title_sort | diastereoselectivity is in the details: minor changes yield major improvements to the synthesis of bedaquiline |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545417/ https://www.ncbi.nlm.nih.gov/pubmed/35675114 http://dx.doi.org/10.1002/chem.202201311 |
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