Application of Stereocontrolled Stepwise [3+2] Cycloadditions to the Preparation of Inhibitors of α₄β₁‐Integrin‐Mediated Hepatic Melanoma Metastasis

Abstract

Inhibitors of the interaction between protein VLA-4 and its natural ligand VCAM-1 have been designed, even though the structure of the protein remains unresolved. The rational design relied on the simulation of the steric and electronic properties of the active loop of VCAM-1, whose structure is known (see picture), and the inhibitors were readily prepared by stereoselective stepwise [3+2] cycloadditions.