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Organocatalytic and Scalable Synthesis of the Anti‐Influenza Drugs Zanamivir, Laninamivir, and CS‐8958
Author(s) -
Tian Junshan,
Zhong Jiankang,
Li Yunsheng,
Ma Dawei
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201408138
Subject(s) - zanamivir , enantioselective synthesis , chemistry , thiourea , combinatorial chemistry , aldehyde , neuraminidase , adduct , catalysis , organic chemistry , medicine , disease , pathology , covid-19 , infectious disease (medical specialty) , enzyme
Zanamivir, laninamivir, and CS‐8958 are three neuraminidase inhibitors that have been clinically used to combat influenza. We report herein a novel organocatalytic route for preparing these agents. Only 13 steps are needed for the assembly of zanamivir and laninamivir from inexpensive D ‐araboascorbic acid by this synthetic route, which relies heavily on a thiourea‐catalyzed enantioselective Michael addition of acetone to tert ‐butyl (2‐nitrovinyl)carbamate and an anti ‐selective Henry reaction of the resulting Michael adduct with an aldehyde prepared from D ‐araboascorbic acid. The synthetic procedures are scalable, as evident from the preparation of more than 3.5 g of zanamivir.