Synthesis of the first α-fluoro-phosphotyrosyl mimetic

The diastereoselective preparation of (2S)-2-fluoro-4-[[bis(1,1- dimethylethoxy)phosphinyl]methyl] benzenepropanoic acid (5) is presented as new phosphotyrosyl (pTyr) mimetic suitably protected for incorporation into peptides. Synthesis of 5 utilized electrophilic fluorination under chiral induction provided by the commercially available Evans auxiliary, (S)-(+)-4-phenyl-2-oxazolidinone. In order to demonstrate its synthetic utility, analogue 5 was employed to prepare a signal transduction-directed tripeptide. The design considerations for this peptide and its preliminary biological evaluation are included.