The invention relates to a semi-synthesis method of semeglutide, and belongs to the field of
chemical synthesis. The semi-synthesis method mainly comprises the following steps: (1) activating a
side chain; (2) connecting an activated
side chain with an Arg34GLP-1 (9-37) 29
peptide; (3) activating the
dipeptide; (4) connection of the activated
dipeptide and the
side chain 29
peptide conjugate; (5) removing a
protecting group to obtain a final product, namely a crude product of the semeglutide; meanwhile, pretreatment of materials and post-treatment of products are optimized in the synthesis process. On one hand, a side chain and
dipeptide activation method which is short in time consumption and high in conversion rate is provided, on the other hand, an intermediate pretreatment and post-treatment method which is convenient, rapid, beneficial to reaction and beneficial to cost reduction and efficiency improvement is provided, the characters of substrates / products in all the steps are improved, cost reduction, production specification expansion and efficiency improvement in industrial production are facilitated, and the method is suitable for industrial production. And the method has very important significance on industrial production of a semeglutide
bulk drug.