Synthetic method for semaglutide

A technology of semaglutide and a synthesis method, which is applied in the field of polypeptide drug synthesis, can solve the problems of destroying the secondary structure of straight-chain peptides, unfavorable to industrialized production, low purity and yield, etc., so as to reduce costs and solve the problem of difficult coupling. , synthesizing simple and easy-to-operate effects

Pending Publication Date: 2019-03-12
SINOPEP ALLSINO BIOPHARMACEUTICAL CO LTD
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Problems solved by technology

[0008] The technical problem to be solved by the present invention is to provide a new synthetic method of semaglutide aiming at the problems of low purity and yield, high cost, cumbersome operation steps and unfavorable industrial production in the existing synthetic process. The method uses the form of dipeptide for coupling, which destroys the secondary structure of the linear peptide, solves the difficult problem of coupling, removes the missing peptide produced by the process, reduces the input material, reduces the cost, and is beneficial to the scale-up production

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  • Synthetic method for semaglutide
  • Synthetic method for semaglutide
  • Synthetic method for semaglutide

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Embodiment Construction

[0047] The technical solutions of the present invention are further described below, so that those skilled in the art can further understand the present invention, without constituting a limitation on the rights of the present invention.

[0048] One, the preparation of Fmoc-Gly-Wang resin

[0049] Weigh 110.0 g of Wang resin (Sub=0.61 mmol / g) and add it to a solid-phase reactor, add 360 mL of DCM to swell the resin for 0.5 h, and drain the solvent. Add 49.1g of Fmoc-Gly-OH and 29.5g of HOBt to 360ml of DMF solution and stir to dissolve. After cooling down to 5-8 degrees, add 29.5mL of DIC solution and stir. Add the activated solution to the resin and stir for 5h. Drain the solvent, add 11 mL of acetic anhydride, 8 mL of pyridine, and 170 mL of DMF, and block for 2 hours. DCM and methanol were alternately washed 3 times, 170 mL each time. After vacuum drying, the substitution degree of Fmoc-Gly-Wang resin is about Sub=0.55mmol / g.

[0050] 2. Fmoc-Val 10 -Ser 11 Preparatio...

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Abstract

The invention discloses a synthetic method for semaglutide and belongs to the field of polypeptide synthesis. In the method, amino acids at 1-30 positions of a main sequence of the semaglutide is obtained by adopting solid phase synthesis, Val at 10 position and Ser at 11 position adopt Fmoc-Val10-Ser11 (Psi(Me, Me) pro)-OH; and an Lys side chain at 20 position adopts Fmoc-Lys(X)-OH. The method comprises the following steps of performing cracking precipitation to obtain a semaglutide crude peptide; and performing purification to obtain the semaglutide. In the method, by introducing the Fmoc-Val10-Ser11 (Psi(Me, Me) pro)-OH to solve the problem of difficult sequence synthesis of the semaglutide, difficult sequence synthesis becomes simple and easy; and meanwhile, the yield is greatly increased, the purity of the crude peptide is greatly improved, the production cost is greatly lowered, and industrial amplification production is facilitated.

Description

technical field [0001] The invention relates to the field of polypeptide drug synthesis, in particular to a synthesis method of semaglutide, a GLP-1 receptor kinetin. Background technique [0002] Chinese name: Sermaglutide; English name: Sermaglutide; peptide sequence: [0003] H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys(Octadecanedioic-γ-Glu-PEG2- PEG2)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH [0004] Semaglutide is a new long-acting GLP-1 analog developed by Novo Nordisk, Denmark. From the amino acid sequence, the 2nd position of the peptide sequence is the unnatural amino acid amino isobutyric acid, and the Lys side chain amino group at the 20th position of the peptide sequence is Modified with PEG, γ-Glu and octadecanedioic acid. Compared with liraglutide, the modified semaglutide has enhanced hydrophilicity, inhibits the hydrolysis of DPP-4 enzyme, prolongs the biological half-life, lowers blood sugar for a long time, pro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/605C07K1/16C07K1/06C07K1/04
CPCC07K14/605Y02P20/55
Inventor 赵呈青谷海涛施国强孙美禄
Owner SINOPEP ALLSINO BIOPHARMACEUTICAL CO LTD
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