Synthesis method of carbetocin

A technology for carbetocin and a synthesis method, applied in the field of polypeptide drug preparation, can solve the problems of poor continuity, unfavorable purification process development, low overall process yield and the like, and achieves reduction of comprehensive production cost, improvement of cyclization reaction efficiency, The effect of process green environmental protection

Active Publication Date: 2020-12-18
NINGBO SANSHENG BIOLOGICAL TECH CO LTD
View PDF17 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Chinese patent applications CN 201110001400.0, CN 201410331088.5, CN 201610189424.6, and CN201610728294.9 disclose the synthesis route of carbetocin. The cyclization method of linear chain peptide is realized by the condensation of carboxyl and amino groups to form amide bonds. Such a technical route requires the use of Sulfhydryl-modified special amino acids have high synthesis costs and are not conducive to large-scale commercial production
[0007] Chinese patent applications CN 201310392663.8, CN 201310412014.X, CN 201410076731.4, CN201410461695...

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Synthesis method of carbetocin
  • Synthesis method of carbetocin

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0050] The synthetic method of carbetocin in some examples of the present invention comprises the following steps:

[0051] (1) With Rink Amide-MBHA Resin as the carrier, after swelling treatment, the protected Gly, protected Leu, protected Pro, protected Cys, protected Asn, protected Gln, protected Ile and protected Tyr were condensed in sequence The reaction is coupled to the swelling Rink Amide-MBHA Resin, and dried to obtain the peptide resin 1;

[0052] (2) Peptide resin 1 reacts with vinyl acetic acid to obtain peptide resin 2, which has the following structure: CH 2 =CH-CH 2 -CO-Tyr(me)-Ile-Gln(Trt)-Asn(Trt)-Cys(Trt)-Pro-Leu-Gly-Rink Amide-MBHA Resin;

[0053] (3) Peptide resin 2 is cracked to obtain carbetocin intermediate I, whose structure is as follows:

[0054] CH 2 =CH-CH 2 -CO-Tyr(me)-Ile-Gln(Trt)-Asn(Trt)-Cys(Trt)-Pro-Leu-Gly-NH 2 ;

[0055] (4) Carbetocin intermediate I was cyclized to obtain carbetocin.

[0056] During the synthesis process, the coupli...

Embodiment 1

[0080] The carbetocin synthesis process of the present embodiment 1 is as follows: figure 1 As shown, specifically:

[0081] (1) Rink Amide-MBHA Resin swelling

[0082] Calculate and weigh 100mmol Rink Amide-MBHA Resin (the degree of substitution is 0.8mmol / g), pour it into the reaction kettle, add DCM in an amount of 20ml / g, and let it stand for swelling for 3 hours.

[0083] Washing: Wash twice with DMF, each time 1.0L, and each washing time is not less than 2min.

[0084] Deprotection: Add 1.0L of 20v / v% piperidine / DMF, stir for 30 minutes, then drain the reaction solution, and the reaction is terminated.

[0085] Washing: Wash twice with DMF, twice with methanol, twice more with DMF, each time with 1.0L, and each time of washing should not be less than 2min.

[0086] (2) Coupling of Fmoc-Gly-OH

[0087] Weigh Fmoc-Gly–OH: 89.25g, HOBt: 40.54g, DIC: 47.33ml.

[0088]Dissolve Fmoc-Gly-OH and HOBt with 300ml DMF, slowly add DIC to the swollen Rink Amide-MBHA Resin for pr...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Degree of substitutionaaaaaaaaaa
Login to view more

Abstract

The invention belongs to the field of polypeptide drug preparation methods, and relates to a synthesis method of carbetocin. The synthesis method of carbetocin comprises the following steps of (1) using Rink Amide MBHA Resin as a carrier, performing swelling treatment, and then, sequentially coupling protected Gly, protected Leu, protected Pro, protected Cys, protected Asn, protected Gln, protected Ile and protected Tys to swell Rink Amide-MBHA Resin through a condensation reaction, and performing drying to obtain peptide resin 1; (2) performing reaction on the peptide resin 1 with vinylaceticacid to obtain peptide resin 2; (3) cracking the peptide resin 2 to obtain a carbetocin intermediate I; and (4) performing cyclization reaction on the carbetocin intermediate I to obtain the carbetocin. The synthesis method has the advantages of high reaction selectivity, quick reaction, few by-products and impurities, high yield, safety, environment protection, simplicity and easy operation.

Description

technical field [0001] The invention belongs to the field of polypeptide drug preparation methods and relates to a synthesis method of carbetocin. Background technique [0002] Carbetocin, a cyclic polypeptide, is a synthetic long-acting nonapeptide analogue of oxytocin with agonist properties. [0003] The molecular formula of carbetocin is C 45 h 69 N 11 o 12 S, the molecular weight is 998.17, the chemical name is: deamin-2-oxo-methyltyrosine-1-к-oxytocin, and the structure is: [0004] [0005] Carbetocin can be administered as a single intravenous dose immediately following epidural or spinal cesarean delivery to prevent uterine hypotonia and postpartum hemorrhage. The clinical and pharmacological properties of carbetocin are similar to those of naturally occurring oxytocin. Like oxytocin, carbetocin binds to the oxytocin receptors of uterine smooth muscle, causing rhythmic contractions of the uterus, increasing its frequency and increasing uterine tension on th...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07K7/16C07K1/08C07K1/06C07K1/04
CPCC07K7/16
Inventor 沙乐陈璐孙慕懿李开刚胡晨良
Owner NINGBO SANSHENG BIOLOGICAL TECH CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap