Method for synthesizing Exenatide from solid phase polypeptide

Abstract

The invention discloses a preparation method of solid phase peptide synthesis Exenatide which includes the following steps: taking Rink Amide resins, Rink Amide AM resins or Rink Amide MBHA resins as starting materials, amino acids with Fmoc protective groups are sequentially connected, so as to obtain protective thirty-nine peptide resins; and meanwhile, after thirty-nine peptide resins are obtained by sequentially removing Fmoc-protective groups and transpeptidase reactions by condensing agents, acellular side-chain protective groups and cutting peptides are carried out sychronously to obtain Exenatide crude products, and then products (comprising medical salts and free alkali, such as acetates, trifluoroacetate, etc.) are obtained after Exenatide crude products are separated and purified by C18 or C8 column and freeze-dried. The preparation method has the advantages of stable technology, conventient raw and auxiliary material sources, short production cycle, low production cost, few three wastes, high yield, stable yield, stable quality, low production cost and high yield.

Description

Technical field [0001] The present invention relates to a preparation method of Exenatide, in particular to a preparation method of solid-phase polypeptide synthesis Exenatide. Background technique [0002] Chinese name: Exenatide, Exenatide acetate. [0003] Product name: BYETTA . English name: Exenatide Acetate. [0004] Structural formula: His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu- Trp(Boc)-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH 2 [0005] The molecular formula is: C 184 H 282 N 50 O 60 S [0006] The molecular weight is: 4186.6 [0007] Diabetes is a worldwide disease. There are more than 150 million diabetic patients in the world, among which 90% are type II diabetic patients. [0008] There are nearly 40 million type II diabetes patients in my country. With the improvement of living standards, the incidence rate will be higher and higher. There are more cities than rural areas. Because patients have...

AI Technical Summary

Problems solved by technology

[0009] U.S. Patent 6,528,486 has reported the method for preparing Exenatide, is to adopt TentaGel S-RAM resin as starting material, uses DIC / HOBt or DCC / HOBt as condensation agent, and the reaction time is long, and TentaGel S-RAM resin source is scarce, and is expensive (is Rink Amide AM resin five times); thus this method limits the large-scale production and use of Exenatide