The invention provides a synthesis method of tilpotide, which comprises the following steps: dividing a
target peptide chain into six fragments, and adopting bis (4-C18-C28 alkoxy phenyl)
methylamine, 2, 4-bis (18-C28 alkoxy)-
benzyl alcohol and NH2-Asp (OTAG)-OR1 as hydrophobic
label carriers to assist synthesis. A
side chain carboxyl group of
aspartic acid is innovatively used as an anchoring position of a hydrophobic
label, a new fragment connection
route is designed, a full-protection tilpotide conjugate is synthesized through a multi-
label synergistic effect, and finally a
protecting group and a label are removed by using a TFA lysate. Compared with a
solid-
phase synthesis method, the method is carried out in a homogeneous reaction, the dosage of
amino acid and the condensing agent is reduced to 1-1.2 times from 2-3 times, and the cost is remarkably reduced. Compared with an existing hydrophobic labeling method, the method has the advantages that multiple labels can be introduced to serve as protecting groups, the yield and purity of synthesis of medium-chain and long-chain polypeptides are improved, meanwhile, the problem of hydrophobicity attenuation caused by
peptide chain extension is solved, and the green
chemical process requirement is met.