A method of synthesis Linaclotide

It is related to medical synthesis field, discloses a kind of method for synthesizing Linaclotide.The side prepares Linaclotide using one step cyclization method of solid phase, the linear peptide resin of Linaclotide directlys adopt N-X without cracking and is cyclized to obtain Linaclotide resin for one step of succinimide solution oxide system progress, resin is cracked, and purifying and freeze-drying obtain Linaclotide.The N-X is one of N-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, N- hydroxy thiosuccinimide for succinimide.The method has the advantage that 1, using solid phase cyclization, plays false dilution effect first, avoids being repetitively folded for peptide chain, can carry out cyclization in higher concentrations, can greatly improve production efficiency；Secondly linear peptide resin is not cracked before cyclisation, avoids the generation of a large amount of impurity, improves the efficiency of Linaclotide cyclisation.2, a step cyclisation is carried out for succinimide using N-X, can avoid the more purification of intermediate, reduces the ingredient of intennediate purification step, improve the total recovery of Linaclotide.3, using specific amino acid side chain protecting group, it located 1 pair of disulfide bond in cyclization process, reduce the generation of mispairing by-product, improve the purity of Linaclotide, can greatly improve production efficiency, reduce production cost.