Different synthetic strategies of oseltamivir phosphate: a potent influenza neuraminidase inhibitor.
Oseltamivir phosphate (Tamiflu) is the only orally active anti-influenza drug that potently inhibit neuraminidase. The recent emergence of avian flu, especially the H5N1 type, makes the situation of Tamiflu supply and demand increasingly serious. Further optimization of the current commercial approach and exploration of new synthetic routes are urgent. Here, different synthetic strategies of oseltamivir phosphate are reviewed, including discovery and improved synthetic route from (-)-quinic acid or (-)-shikimic acid, new asymmetric synthesis via catalytic desymmetrization of a meso-aziridine (CDMA), Diels-Alder Reaction and from other available materials.
Gong
Jianzhi
J
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, ShanDong University, 44, West Culture Road, 250012, Ji'nan, ShanDong, P.R. China.
Xu
Wenfang
W
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D007251:Influenza, Human / Q000201:enzymology*; D008968:Molecular Conformation; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053139:Oseltamivir / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase