The present inventors when carried out the reaction of (3-31) amino acid fragment of Semaglutide having the amino acid sequence Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser- Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly with PGi-His(PG)-Aib-OH and further converted the obtained compound to Semaglutide surprisingly found that the said process efficiently controlled the formation of D-His, Des- His, Des-Aib, Di-Aib, Des-Aib-His impurities in the Semaglutide API which is highly advantageous on industrial scale especially for complex peptide molecules like Semaglutide
10 is a liquid chromatogram of semaglutide obtained in example 9
The diluent in the present invention is selected from but not limited to methanol: water, ethanol: water, acetonitrile:water, isopropanol: water and the like
[0026] In the present invention, an acidic TFA solution is to be used to remove Mmt and Mtt protecting groups 6-12 times, which increases the complexity of the operation
Example 8 Arg34GLP-1 (9-37) carries out the modification of terminal amino group: 1g Boc-His (Trt) -Aib-OH was dissolved in 10mL dichloromethane and 0.34g p-nitrophenol was added
