title: Synthesis of N-tert.-butoxycarbonyl-( alpha-phenyl)aminomethylphenoxyacetic acid for use as a handle in solid-phase synthesis of peptide alpha-carboxamides.
abstract: N-tert.-butoxycarbonyl-aminomethyl( alpha-phenyl)phenoxyacetic acid was synthesized and found to be suitable for use as a handle in the solid-phase synthesis of peptide alpha-carboxamides. This handle was prepared with an 82% yield when N-tert.-butoxycarbonyl-( rho-hydroxy)benzhydrylamine was treated with excess sodium iodoacetate under alkaline conditions. In stability studies the linkage between the C-terminal amino acid and the handle was found to be resistant to acidolysis in 50% TFA/CH2Cl2 (less than 1% loss after 10h). Upon treatment for 30 min with HF:anisole(9:1) at 0 degrees, 92% cleavage of glycinamide from Gly-handle-resin was obtained. In a test synthesis of a peptide alpha-carboxamide, pyroglutamylhistidylprolinamide was synthesized in 83% yield. Two other handles, tert.-butoxycarbonyl-aminomethylphenoxyacetic acid and N-tert.-butoxycarbonyl-aminomethylphenyloxymethylphenoxyacetic acid, were also synthesized but found to be unsuitable for carboxamide synthesis under the same conditions of solid-phase synthesis.
mesh_terms: D006016:Glycolates / Q000138:chemical synthesis*; D010455:Peptides / Q000138:chemical synthesis*; D012117:Resins, Synthetic / Q000138:chemical synthesis*
chemical_list: D006016:Glycolates; D010455:Peptides; D012117:Resins, Synthetic