Angew. Chem. Int. Edn doi:10.1002/anie.200804883 (2009)

With the constant threat of a flu pandemic, the quest for cheaper, more efficient routes by which to make the flu treatment Tamiflu is keeping chemists busy. Yujiro Hayashi and his team at the Tokyo University of Science report the highest-yielding route so far using inexpensive reagents and just nine reactions, all in three one-pot processes.

The first pot uses diphenylprolinol silyl ether, an organocatalyst — a class of catalysts that don't involve expensive and toxic metals. The organocatalyst helps the first two starting materials to react, and they go on to react with a third. The product goes into pot two to undergo a domino reaction — a cascade of reactions whereby each group of a molecule with many functional groups reacts in turn. In pot three, the final three reactions produce Tamiflu, or (−)-oseltamivir, in 57% yield.

The authors say that their scheme is ideal for large-scale production.