A novel and high-yielding asymmetric synthesis of oseltamivir phosphate (Tamiflu) starting from (-)-shikimic acid

作者：Nie, Liang-Deng; Ding, Wei; Shi, Xiao-Xin^*; Quan, Na; Lu, Xia

来源：Tetrahedron: Asymmetry , 2012, 23(10): 742-747.

DOI：10.1016/j.tetasy.2012.05.014

• NEURAMINIDASE INHIBITOR OSELTAMIVIR
• POTENT ANTIINFLUENZA ACTIVITY
• RING-CLOSING METATHESIS
• AZIDE-FREE SYNTHESIS
• SHIKIMIC ACID
• CHEMOENZYMATIC SYNTHESIS
• EFFICIENT SYNTHESIS
• CONCISE SYNTHESIS
• PRACTICAL SYNTHESIS
• ETHYL-ESTER

A novel and high-yielding asymmetric synthesis of oseltamivir phosphate 1 (Tamiflu(R)) is described. The target compound 1 was obtained in 55% overall yield via an 11-step asymmetric synthesis starting from the naturally abundant (-)-shikimic acid. The present synthesis is characterized by some advantages such as the easy separation of intermediate 6 from triphenylphosphine oxide by using its large water-solubility, the use of inexpensive reagents throughout the synthesis, the lack of toxic heavy metals, mild reaction conditions and high yields for all steps. The stereochemical structure of the key intermediate 6 was unequivocally confirmed by X-ray crystallographic analysis.

• 出版日期2012-5-31
• 单位华东理工大学