Enantioselective aza-Michael Cyclization Reaction Catalyzed by Quinine-Derived Monoquaternary Ammonium Salts: an Effective Route to Synthesize Letermovir

Abstract A series of mono- or bis-quaternary ammonium salts derived from cinchonidine or quinine was synthesized and screened as potent phase-transfer catalysts for the reaction of aza-Michael cyclization, the key step in the synthesis of letermovir. During the reaction of aza-Michael cyclization, t...

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Bibliographic Details
Published in:Pharmaceutical fronts 2021-12, Vol.3 (4), p.e194-e199
Main Authors: Chen, Liang, Liu, Wei-Yuan, Bi, Si-Ju, Zhou, Ting, Pan, Jing, Lv, Xun-Lei, Lin, Kuai-Le, Zhou, Wei-Cheng
Format: Article
Language:English
Subjects:
aza-michael cyclization
enantioselective
letermovir
monoquaternary ammonium salts
Original Article
phase-transfer catalyst
racemization
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Summary:Abstract A series of mono- or bis-quaternary ammonium salts derived from cinchonidine or quinine was synthesized and screened as potent phase-transfer catalysts for the reaction of aza-Michael cyclization, the key step in the synthesis of letermovir. During the reaction of aza-Michael cyclization, the screened monoquaternary ammonium salt quinine derivative Q1 transferred 7 to 8 with 91.9% yield and 58% ee . The application of Q1 was preferred, due to its enantioselectivity, the possibility of reuse, and the lower cost in large-scale preparation. Furthermore, the racemization condition of letermovir enantiomer was also explored for the possibility to develop the resolution/racemization process. With the optimal catalyst Q1 in hand, the synthesis of letermovir may be more convenient and economical in the future.
ISSN:2628-5088
2628-5096
DOI:10.1055/s-0041-1740944