Synthesis of the First α‐Fluoro‐Phosphotyrosyl Mimetic

Abstract

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.

Keywords:

• Chiral induction
• Enantioselective
• Phosphotyrosyl mimetic
• Fluorination