Comparative use of benzhydrylamine and chloromethylated resins in solid-phase synthesis of carboxamide terminal peptides. Synthesis of oxytocin derivatives

摘要: Specifically deuterated derivatives of the peptide hormone oxytocin were synthesized by solid-phase method synthesis using either standard chloromethylated resin or benzhydrylamine as support for syntheses, and a comparison overall efficiency syntheses on two resins was made. (1-Hemi-DL-(..beta..,..beta..-/sup 2/H/sub 2/) cystine) resin, diastereomers separated purified partition chromatography gel filtration in an yield about 30%. (1-Hemi-DL-(..cap alpha..-/sup 1/) prepared to prepare nonapeptide precursor, but otherwise essentially identical conditions used resin. Again filtration. The under best 49%. For latter compounds, S-3,4-dimethylbenzyl protecting groups introduce cysteine residues. yields substantially improved if HF reactions run at lower temperatures (0/sup 0/C rather than 25/sup 0/C), S-benzyl group usedmore » protection. Reproducible procedures preparing with amino substitution levels 0.15-0.45 mmol group/g developed.« less