Synthesis of α, α-disubstituted 4-phosphonophenylalanine analogues as conformationally-constrained phosphotyrosyl mimetics

Abstract Syntheses of N -Boc ( S )-4-(diethylphosphono)-(α-methyl)phenylalanine [Boc-(α-Me)Phe(4-PO 3 Et 2 )-OH] ( 9 ) and N -Boc ( S )-2-amino-6-(diethylphosphono)tetralin-2-carboxylic acid [Boc-Atc(6-PO 3 Et 2 )-OH] ( 18 ) are reported as conformationally-constrained phosphotyrosyl mimetics suitably protected for peptide synthesis. Both syntheses proceeded through chiral arylhalides that are converted to arylphosphonates by palladium-catalyzed cross coupling with diethylphosphite. These amino acid analogues may be useful in the study of cellular signal transduction processes.