Sugar‐Based Synthesis of Tamiflu and Its Inhibitory Effects on Cell Secretion |
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| Authors: | Jimei Ma Yanying Zhao Simon Ng Jing Zhang Jing Zeng Aung Than Peng Chen Prof Dr Xue‐Wei Liu Prof Dr |
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| Institution: | 1. Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Fax:?(+65)?67911961;2. Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Avenue, Singapore 637457, Fax:?(+65)?67911761 |
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| Abstract: | 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. |
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| Keywords: | carbohydrates cell secretion inhibitors tamiflu total synthesis |
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