Preparation method of terlipressin impurity Q

Abstract

The invention relates to the technical field of polypeptide synthesis, in particular to a preparation method of a terlipressin impurity Q. The preparation method comprises the following steps: firstly synthesizing a polypeptide fragment I and a polypeptide fragment II which are good in stability, then carrying out disulfide bond exchange on SH of a fourth Cys residue at the C end of the polypeptide fragment I and SNpys or SPyr of the fourth Cys residue at the C end of the polypeptide fragment II through condensation reaction to form a first pair of disulfide bonds, and carrying out iodine oxidation reaction to form a second pair of disulfide bonds while removing an Acm protecting group of the Cys. Experiments show that the terlipressin impurity Q obtained by the preparation method is high in purity and few in impurity, and the purity of a crude product can reach 75% or above.

Description

technical field

[0001] The invention relates to the technical field of polypeptide synthesis, in particular to a preparation method of terlipressin impurity Q. Background technique

[0002] Terlipressin is a synthetic analog of a hormone secreted by the posterior pituitary gland. It can be hydrolyzed by enzymes in the human body to generate vasopressin, which has a contracting effect on smooth muscle. It is mainly used clinically to treat esophageal varices bleeding. Its peptide sequence is as follows:

[0003]

[0004] Terlipressin can generate impurities Q during the preparation and storage process, which can affect the safety of the drug. In the process of developing the terlipressin production process, it is necessary to prepare a reference substance of impurity Q for the study of its product quality.

[0005] The peptide sequence of impurity Q is as follows:

[0006]

[0007] At present, a large number of literatures in the prior art report the preparation met...

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