Synthesis of a New Conformation-Constrained L-Tyrosine Analoque as a Potential Scaffold for SH2 Domain Ligands.

The enantioselective synthesis of a new tricyclic tyrosine analogue is reported. This conformationcontrained SH2 domain ligand scaffold 2 was designed on the basis of the natural ligand, whose structure contains the elements of a tyrosine moiety having Χ¹ and Χ² angles constrained to values observed for a phosphotyrosyl (pTyr) residue bound to the p56[sup lck] SH2 domain. It represents a unique, highly constrained amino acid, which may be of value in signal transduction studies. Three key steps, an asymmetric tandem Michael addition, an intramolecular Friedel-Crafts reaction, and an intramolecular Mannich reaction, were successfully applied in the presented synthetic route. [ABSTRACT FROM AUTHOR]