Migrastatin analogues with an (E)-alkene at the ring C-3: Synthesis, conformational analysis and biological evaluation

In this paper the synthesis of one acyclic and four macrocyclic analogues with an E-alkene at C-3 is described. The route involves ring-closing metathesis, which gave ca. 1:1 mixtures of stereoisomeric alkenes. The crystal structure for a macrolactam with an E-alkene at C-3 and Z-alkene at C-8 was obtained with a brief study of macrocycle conformation by molecular mechanics and coupling constant analysis. Amide rotamers are also observed by NMR spectroscopy. Preliminary in vitro biological study indicates that the new compounds may have limited potential as inhibitors of tumor cell migration.