Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline**
Name
Chemistry A European J - 2022 - Mear - Diastereoselectivity is in the Details Minor Changes Yield Major Improvements to.pdf
Description
Published version
Size
3.03 MB
Format
Adobe PDF
Checksum (MD5)
326885108af6592c5cfddcb4b4cbf97f
Author(s)
Mear, Sarah Jane
Lucas, Tobias
Ahlqvist, Grace P
Robey, Juliana MS
Dietz, Jule‐Philipp
Khairnar, Pankaj V
Maity, Sanjay
Williams, Corshai L
Snead, David R
Nelson, Ryan C
Date Issued
August 22, 2022
Journal
Chemistry – A European Journal
Publisher
Wiley
Citation
Mear, Sarah Jane, Lucas, Tobias, Ahlqvist, Grace P, Robey, Juliana MS, Dietz, Jule‐Philipp et al. 2022. "Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline**." Chemistry – A European Journal, 28 (47).
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/chem.202201311
