L-O-(2-MALONYL)TYROSINE (L-OMT) A NEW PHOSPHOTYROSYL MIMIC SUITABLY PROTECTED FOR SOLID-PHASE SYNTHESIS OF SIGNAL-TRANSDUCTION INHIBITORY PEPTIDES

A new phosphotyrosyl (pTyr) mimic L-O-(2-malonyl)tyrosine (L-OMT, 4) utilizes a malonyl structure in place of the parent phosphate group. This compound is stable to protein-tyrosine phosphatases and has advantages over phosphonate-based pTyr mimics in that protection of the malonyl group as its diester allows passage of the OMT across cell membranes, with subsequent esterase-mediated liberation of the free diacid once inside cells. Herein is reported the synthesis of N-alpha-Fmoc-L-OMT-O,O-(tert-butyl)(2) (5) for the solid-phase synthesis of L-OMT containing peptides as modulators of cellular signal transduction. Additionally included is the preparation of N-alpha-Fmoc-L-OMT-O,O-(n-butyl)(2) (6) for the direct solid-phase synthesis of OMT-peptide diester prodrugs for use in cell-based studies.