Stereoselective synthesis of (S)-MPPG, (S)-MTPG and (S)-(+)-αM4CPG from (R)-4-hydroxyphenylglycine

(R)-4-Hydroxyphenylglycine was protected with a benzyl group and a methyl group was introduced at the a position by using the self-regeneration-of-stereocentre method. After the 4-hydroxy group had been converted into the corresponding trifluoromethanesulfonate (triflate), three palladium-catalyzed reactions were employed to furnish (S)-alpha-methyl-4-phosphonophenylglycine [(S)-MPPG], (S)-alpha-methyl-4-(tetrazol-5-yl)phenylglycine [(S)-MTPG] and (S)-4-carboxyphenyl-alpha-methylglycine [(S)-alpha M4CPG], a class of new and selective antagonists of metabotropic glutamate receptors.