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 rearrangement with PhI(OAc)2, and a domino transformation of the bicyclo[2.2.2] system into an aziridine compound.