BIVALIRUDIN PREPARATION METHOD

摘要

Provided is a bivalirudin preparation method, comprising: preparation of a bivalirudin resin by a solid phase polypeptide synthesis, acidolysis of the bivalirudin resin to give a crude bivalirudin, and purification of the crude bivalirudin to give purified bivalirudin, wherein the method for preparing the bivalirudin resin by the solid phase polypeptide synthesis is carried out by linking the corresponding Fmoc-protected amino acids in order into the following sequence on a Fmoc-Leu-carrier resin through a solid phase coupling synthesis, to give the bivalirudin resin: R1-D-Phe-Pro-Arg(Pbf)-ProX-Asn(R2)-Gly-Asp(OtBu)-Phe-Glu(OtBu)-Glu(OtBu)-Ile-Pro-Glu(OtBu)-Glu(OtBu)-Tyr(tBu)-Leu-resin, and the solid phase coupling synthetic reaction is carried out once only for linking of an X fragment, with the corresponding Fmoc-protected amino acids being Fmoc-Gly-Gly-Gly-Gly-OH. The product has a purity of higher than 99.5% with a single impurity of less than 0.2%.