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Sugar‐Based Synthesis of Tamiflu and Its Inhibitory Effects on Cell Secretion
Author(s) -
Ma Jimei,
Zhao Yanying,
Ng Simon,
Zhang Jing,
Zeng Jing,
Than Aung,
Chen Peng,
Liu XueWei
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200902048
Subject(s) - exocytosis , secretion , chemistry , oseltamivir , claisen rearrangement , combinatorial chemistry , pharmacology , side chain , stereochemistry , biochemistry , biology , organic chemistry , covid-19 , medicine , disease , infectious disease (medical specialty) , polymer
Tamiflu is currently the most effective drug for the treatment of influenza, but the insufficient supply and side‐effects of this drug demand urgent solutions. We present a practical synthesis of Tamiflu by using novel synthetic routes, cheap reagents, and the abundantly available starting material D ‐glucal. The strategy features a Claisen rearrangement of hexose to obtain the cyclohexene backbone and introduction of diamino groups through tandem intramolecular aziridination and ring opening. In addition, this synthetic protocol allows late‐stage functionalization for the flexible synthesis of Tamiflu analogues. By using the synthesized Tamiflu and its active metabolite (oseltamivir carboxylate), we investigated their influences on neuroendocrine PC12 cells in various aspects. It was discovered that oseltamivir carboxylate significantly inhibits the vesicular exocytosis (regulated secretion) of PC12 cells, and suggests a mechanism underlying the Tamiflu side‐effects, in particular its possible adverse influences on neurotransmitter release in the central nervous system.