Desymmetrization-Initiated Stereocontrolled Synthesis of (-)-Kaitocephalin

A total synthesis of (-)-kaitocephalin (1), the first naturally isolated glutamate receptor antagonist, is described. The key steps involved the enantioselective desymmetrization of the N-Cbz-protected seriol 42 to install the C4 quaternary chiral center and the intramolecular mercury(II)-mediated N-cyclization of (Z)-alkene 44 followed by reductive demercuration to construct the pyrrolidine ring. As proposed, the quaternary asymmetric carbon induced the stereoselective epoxidation as well as the regioselective epoxide opening to generate the C2 and C3 stereocenters.