Synthesis of a new conformation-constrained L-tyrosine analogue as a potential scaffold for SH2 domain ligands.
The enantioselective synthesis of a new tricyclic tyrosine analogue is reported. This conformation-constrained SH2 domain ligand scaffold 2 was designed on the basis of the natural ligand, whose structure contains the elements of a tyrosine moiety having chi(1) and chi(2) angles constrained to values observed for a phosphotyrosyl (pTyr) residue bound to the p56(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.
Liu
Fa
F
State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, 354 Fenglin Road, Shanghai 200032, China.
Zha
Hui-Yan
HY
Yao
Zhu-Jun
ZJ
D007202:Indicators and Reagents; D013058:Mass Spectrometry; D008958:Models, Molecular; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D018909:src Homology Domains
D007202:Indicators and Reagents; D014443:Tyrosine