Design and synthesis of a reagent for solid-phase incorporation of the phosphothreonine mimetic (2 S ,3 R )-2-amino-3-methyl-4-phosphonobutyric acid (Pmab) into peptides in a bio-reversible phosphonyl- bis -pivaloyloxymethyl (POM) prodrug form

Reported herein are the synthesis and solid-phase peptide incorporation of N -Fmoc-(2 S ,3 R )-2-amino-3-methyl-4-phosphonobutyric acid bis -pivaloyloxymethyl phosphoryl ester [Fmoc-Pmab(POM) 2 -OH, 2 ] as a phosphatase-stable phosphothreonine (pThr) mimetic bearing orthogonal protection suitable for the synthesis of Pmab-containing peptides having bio-reversible protection of the phosphonic acid moiety. This represents the first report of a bio-reversibly protected pThr mimetic in a form suitable for facile solid-phase peptide synthesis.