Total Synthesis of Aliskiren: The First Renin Inhibitor in Clinical Practice for Hypertension

We report a macrocycle route toward aliskiren, a drug presently marketed for the treatment of hypertension, using a highly stereocontrolled approach starting from a common isopropyl chiron. Highlights of the synthesis include a challenging RCM reaction to produce a nine-membered unsaturated lactone, a highly stereoselective catalytic Du Bois aziridination, and a regio- and diastereoselective aziridine ring-opening to a vicinal amino alcohol.