LIRAGLUTIDE SYNTHESIS Russian patent published in 2022 - IPC C07K14/605 C07K1/06 C07K1/10 

FIELD: chemistry.

SUBSTANCE: invention relates to the effective solid-phase synthesis of liraglutide represented by the Formula-I. A method includes following stages: a) loading of C-terminal glycine onto resin-based solid-phase substrate in the presence of a binding agent; b) capping of unreacted functional sites; c) sequential binding of N^α-protected amino acids and amino acids with protected side chains to obtain a liraglutide backbone in the presence of the binding agent and inorganic salt; d) removal of the protective group of the lysine side chain; e) binding of glutamic acid and palmitic acid to the lysine side chain in the presence of the binding agent and inorganic salt; and f) obtaining crude liraglutide by removing protective groups and cleaving peptide from resin; where the method includes binding of amino acids 9-13 at an elevated temperature in the range from 30 to 45°C, where the specified inorganic salt is present as a catalyst and is selected from a group consisting of magnesium chloride, zinc chloride and copper chloride, where the stage (c) includes the removal of Fmoc protection of each loaded amino acid using piperidine in DMF (N,N'-dimethylformamide) or a mixture of piperidine/DBU (1,8-diazabicyclo[5.4.0]undets-7-en)/DMF, where, after each stage of removal of Fmoc protection, a washing stage is carried out using HOBt (N-hydroxybenzotriazole) in DMF, as well as removal of the methyl trityl protective group of lysine.

EFFECT: method provides avoiding deletion of sequences and leads to an increase in yield.

12 cl, 2 dwg, 7 ex