A Stereoselective Synthesis of the ACE Inhibitor Trandolapril

A conceptually novel and stereoselective synthesis of the enantiopure octahydroindole building block and its conversion into the ACE inhibitor trandolapril was achieved. Key steps include the α-allylation of a protected l -pyroglutamic acid derivative, a highly diastereoselective Hosomi–Sakurai reaction and a Ru-catalyzed ring-closing metathesis of a 4,5-diallylated proline. This way, the synthesis of trandolapril was efficiently achieved in 25% overall yield (12 steps).