IMPROVED PROCESS FOR PREPARATION OF EPTIFIBATIDE BY FMOC SOLID PHASE SYNTHESIS

摘要

Eptifibatide is a cyclic heptapeptide containing six amino acids and one mercaptopropionyl (des-aminocysteine, Mpa) residue. An interchain disulphide linkage is formed between the cystiene amide and mercaptopropionyl moieties. It is a short acting parenteral antithrombotics drug used for treating Acute Coronary Syndrome (ACS). The present invention describes, simple, convenient, economical process for preparation of eptifibatide by Fmoc solid phase peptide synthesis. The linear peptide is assembled on Rink amide resin, in which thiol groups of cysteine and mercaptopropionic acid are protected by acm group and guanidine of homoarginine by pbf group. The assembled peptide is cleaved from the resin to give linear peptide in which thiols of cysteine and mercaptopopionic acid are protected by acm group. The linear peptide is oxidized by mild oxidation reagent iodine leading to afford eptifibatide. A three-stage HPLC purification afforded pharmaceutical grade eptifibatide with purity greater than 99%.