Total synthesis of the novel immunosuppressant sanglifehrin A

The total synthesis of the novel immunosuppressant sanglifehrin A (SFA, 1) is described. The approach is flexible, convergent, and stereoselective. The use of Paterson's aldol methodology was pivotal for the preparation of the novel, highly substituted spirolactam fragment of SFA. The 22-membered macrocyclic core of the molecule and the coupling of this fragment to the spirolactam moiety were successfully achieved using selective intra- and intermolecular Stille reactions, respectively. Carbodiimide-based protocols were employed for the synthesis of the tripeptide backbone.