Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Sarah Jane Mear
- Tobias Lucas
- Grace P Ahlqvist
- Juliana MS Robey
- Jule-Philipp Dietz
- Pankaj V Khairnar
- Sanjay Maity
- Corshai L Williams
- David R Snead
- Ryan C Nelson
- Till Opatz
- Timothy F Jamison
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000821524800001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1002/chem.202201311
- eISSN
- 1521-3765
- Externe Identifier
- Clarivate Analytics Document Solution ID: 3Y6UX
- PubMed Identifier: 35675114
- ISSN
- 0947-6539
- Ausgabe der Veröffentlichung
- 47
- Zeitschrift
- CHEMISTRY-A EUROPEAN JOURNAL
- Schlüsselwörter
- bedaquiline
- continuous flow
- diastereoselectivity
- lithiation
- nucleophilic addition
- Artikelnummer
- ARTN e202201311
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Titel
- Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline
- Sub types
- Article
- Ausgabe der Zeitschrift
- 28
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:p>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.</jats:p>
- Autoren
- Sarah Jane Mear
- Tobias Lucas
- Grace P Ahlqvist
- Juliana MS Robey
- Jule‐Philipp Dietz
- Pankaj V Khairnar
- Sanjay Maity
- Corshai L Williams
- David R Snead
- Ryan C Nelson
- Till Opatz
- Timothy F Jamison
- DOI
- 10.1002/chem.202201311
- eISSN
- 1521-3765
- ISSN
- 0947-6539
- Ausgabe der Veröffentlichung
- 47
- Zeitschrift
- Chemistry – A European Journal
- Sprache
- en
- Online publication date
- 2022
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Herausgeber
- Wiley
- Herausgeber URL
- http://dx.doi.org/10.1002/chem.202201311
- Datum der Datenerfassung
- 2023
- Titel
- Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline**
- Ausgabe der Zeitschrift
- 28
Datenquelle: Crossref
- Abstract
- 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.
- Addresses
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
- Autoren
- Sarah Jane Mear
- Tobias Lucas
- Grace P Ahlqvist
- Juliana MS Robey
- Jule-Philipp Dietz
- Pankaj V Khairnar
- Sanjay Maity
- Corshai L Williams
- David R Snead
- Ryan C Nelson
- Till Opatz
- Timothy F Jamison
- DOI
- 10.1002/chem.202201311
- eISSN
- 1521-3765
- Externe Identifier
- PubMed Identifier: 35675114
- PubMed Central ID: PMC9545417
- Funding acknowledgements
- National Science Foundation: 1745302
- Bill and Melinda Gates Foundation:
- Open access
- true
- ISSN
- 0947-6539
- Ausgabe der Veröffentlichung
- 47
- Zeitschrift
- Chemistry (Weinheim an der Bergstrasse, Germany)
- Schlüsselwörter
- Humans
- Mycobacterium tuberculosis
- Tuberculosis
- Antitubercular Agents
- Reproducibility of Results
- Diarylquinolines
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2022
- Open access status
- Open Access
- Paginierung
- e202201311
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2022
- Titel
- Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 28
Files
https://dspace.mit.edu/bitstream/1721.1/145710/2/Chemistry A European J - 2022 - Mear - Diastereoselectivity is in the Details Minor Changes Yield Major Improvements to.pdf https://europepmc.org/articles/PMC9545417?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- 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.
- Autoren
- Sarah Jane Mear
- Tobias Lucas
- Grace P Ahlqvist
- Juliana MS Robey
- Jule-Philipp Dietz
- Pankaj V Khairnar
- Sanjay Maity
- Corshai L Williams
- David R Snead
- Ryan C Nelson
- Till Opatz
- Timothy F Jamison
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/35675114
- DOI
- 10.1002/chem.202201311
- eISSN
- 1521-3765
- Externe Identifier
- PubMed Central ID: PMC9545417
- Funding acknowledgements
- National Science Foundation: 1745302
- Bill and Melinda Gates Foundation:
- Ausgabe der Veröffentlichung
- 47
- Zeitschrift
- Chemistry
- Schlüsselwörter
- bedaquiline
- continuous flow
- diastereoselectivity
- lithiation
- nucleophilic addition
- Antitubercular Agents
- Diarylquinolines
- Humans
- Mycobacterium tuberculosis
- Reproducibility of Results
- Tuberculosis
- Sprache
- eng
- Country
- Germany
- Paginierung
- e202201311
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2022
- Titel
- Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 28
Datenquelle: PubMed
- Beziehungen:
- Eigentum von