IMPROVED PROCESS FOR PREPARATION OF BIVALIRUDIN

摘要

Bivalirudin is 20 amino acids containing polypeptide and used as anticoagulant. The present invention describes simple, cheap, convenient process for preparation of bivalirudin by solid phase synthesis using fmoc chemistry. The linear peptide was assembled on chlorotrityl chloride polystyrene resin. The assembled peptide was cleaved by trifluoroacetic acid to yield novel nitro protected bivalirudin, where guanidine of arginine was protected by nitro group. The nitro group in nitro protected bivalirudin was cleaved by formic acid - Pd/C to give crude bivalirudin. The reagent and conditions used in this reaction was environment friendly. The crude bivalirudin was purified by three stage preparative HPLC to yield bivalirudin with purity greater than 99%.