Isocomplestatin: total synthesis and stereochemical revision

A Pd-mediated method for preparation of the strained macrocyclic moiety of complestatins is disclosed. Through stereoselective synthesis of model macrocycles and the S atropisomer of complestatin, the stereochemical identity of the anti-HIV agent complestatin is established. Investigations described herein illustrate that the compound previously reported as isocomplestatin is the same as complestatin. Thus, the S atropisomer of complestatin is the true isocomplestatin and has not been isolated as a natural product.