A new and efficient asymmetric synthesis of oseltamivir phosphate (Tamiflu) from d-mannose

Oseltamivir phosphate (Tamiflu) was synthesized from d-mannose through a short and practical synthetic route. A unique feature of the route is that the bulky 3-pentyloxy group and adjacent acetamide of Tamiflu were introduced at an early stage of the synthesis by copper-catalyzed regioselective ring-opening of the 2,3-pentylidene ketal of d-lyxofuranoside. The d-lyxofuranoside ethylphosphonate precursor was then cyclized via an intramolecular Horner–Wadsworth–Emmons reaction to furnish the Tamiflu skeleton.