Practical Synthesis of Tamiflu and Beyond
Influenza viruses pose a serious threat to world public health. In particular, the currently spreading avian H5N1 virus strain is a great menace because of its high lethality rate, and strains of this virus have already spread to many countries in Asia, Europe, and Africa. There are now increasing concerns that this virus might acquire infectious ability among humans, leading to a worldwide pandemic. Two of the drugs currently used to treat influenza patients are Tamiflu [(−)-oseltamivir phosphate; Fig. 1, 1]  and Relenza (zanamivir) , both of which inhibit viral neuraminidase. Tamiflu is an orally active prodrug, whereas Relenza has low bioavailability and is administered by inhalation. Because neuraminidase is a fundamental enzyme for the life cycle of general influenza viruses, the neuraminidase inhibitors are effective against all influenza virus types including H5N1.
KeywordsInfluenza Virus Shikimic Acid Alder Reaction Dimethyl Fumarate Allyl Ester
I thank Professor Masakatsu Shibasaki for his kind support and guidance of this project. I also thank Drs. Kenzo Yamatsugu, Liang Yin, Shin Kamijo, Mr. Yasuaki Kimura, and Kenta Saito of The University of Tokyo for their contribution. Professor Takashi Kuzuhara and Dr. Noriko Echigo are acknowledged for collaboration. This work was partly supported by the Uehara Memorial Foundation.
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