A Convergent Synthesis of the Macrocyclic Core of Cytotrienins: Application of RCM for Macrocyclization

[reaction: see text] The asymmetric synthesis of the fully elaborated macrocyclic core of cytotrienins A-D, potent apoptosis-inducing agents, is described. Synthetic highlights include the construction of the aniline bond using a copper-mediated amidation and the use of a ring-closing metathesis (RCM) reaction to efficiently install the (E,E,E)-triene and simultaneously construct the macrocyclic lactam.