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DOI: 10.1055/a-2673-5110
Practical and Scalable Synthesis of Cisatracurium Besylate
Funding None.
Abstract
Cisatracurium besylate (1) is a potent nondepolarizing neuromuscular blocking agent utilized in clinical anesthesia. Its primary synthetic challenges arise from its four chiral centers and its unstable properties. We herein attempt to explore a practical and scalable method for the enantioselective synthesis of 1. In this work, 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline (8) was used as a starting material. R-tetrahydropapaverine (R-6) was generated through a Ru-catalyzed asymmetric transfer hydrogenation reaction with 77.0% yield, 99.45% purity, and 99.67% ee. This was a key step. The control of the chiral nitrogen can be achieved through an N-methylation process to produce (R-cis)-10 with 41.6% yield, 99.08% purity, and gratifying enantioselectivity (100% de) through a simple and repeatable recrystallization. The process can be utilized to produce 1 without chromatography purification in five steps with an HPLC purity of 98.71% on a 100-g scale. The process was easy to implement and suitable for manufacturing-scale production.
# These authors contributed equally to this work.
Publication History
Received: 25 March 2025
Accepted: 31 July 2025
Article published online:
21 August 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Georg Thieme Verlag KG
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