Solid-Phase Synthesis of Amino- and Carboxyl-Functionalized Unnatural α-Amino Acid Amides

A new solid-phase synthesis efficiently incorporates three different substituents (from R1-X, R2-CO2H, and R3-NH2) into a glycine-based peptidomimetic scaffold. The synthetic sequence is general and is typically accomplished in >50% overall isolated yield. Alkylating agents with a range of reactivities and normal and branched primary amines give good results. Utility was demonstrated by the synthesis of a series of protected phosphotyrosine mimetics.