Stereoselective synthesis of new modified conformationally constrained l-tyrosine analogue with potential applications to SH2 domain ligands

This paper reports the stereoselective synthesis of a modified tricyclic tyrosine analogue 3, whose conformation is constrained by the covalent bonds and designed on the basis of X-ray and solution structures of SH2 domain and its natural peptide ligand. A Michael addition followed by an alkylation in high stereoselections, a Friedel-Crafts and a Mannich reaction-based cyclization served as the key steps in the synthesis.