A practical synthesis of (-)-oseltamivir

Oseltamivir phosphate (Tamiflu*) is a potent inhibitor of neuraminidase, and is used worldwide as a drug for type A or B influenza. The industrial synthesis of oseltamivir uses shikimic acid as a starting material, but the price fluctuates, depending on the Supply Of star anise. We have developed a practical synthesis of oseltamivir from pyridine, which features an asymmetric Diels-Alder reaction OF dihydropyridine using MacMillan's catalyst, a bromolactonization, Hofmann rcarrangement with Phl(OAc)(2), and a domino transformation of the bicyclo|2.2.2| system into an aziridine compound. (C) 2008 Elsevier Ltd. All rights reserved.