Supercharge Your Innovation With Domain-Expert AI Agents!

Preparation method of suc-ile-glu(γ-pip)-gly-arg-pna hcl

A 2-pna, reaction technology, which is applied in the preparation methods of peptides, chemical instruments and methods, production of bulk chemicals, etc., can solve the problems of major human body or the environment, potential safety hazards, high toxicity of nitroaniline, etc. Low cost, improved stability, and environmentally friendly preparation

Active Publication Date: 2021-09-03
SHANGHAI SUNBIO TECH
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But this method has own defect: the one, the toxicity of p-nitroaniline is very big, has great safety hazard to human body or environment during use; Clearly adversely affects mass production
However, the protective groups mentioned above all have the property of being removed under acidic or alkaline conditions, which is obviously not conducive to the synthesis of peptides.

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
  • Preparation method of suc-ile-glu(γ-pip)-gly-arg-pna hcl

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0026] The preparation method of S-2732 provided by the invention comprises:

[0027] Hydrogen peroxide, trifluoroacetic anhydride and Fmoc-Arg(Alloc) 2 -pPDA reaction to produce Fmoc-Arg(Alloc) 2 -pNA;

[0028] Fmoc-Arg(Alloc) 2 -pNA is sequentially condensed with Gly, Ile-Glu (γ-pip) and succinic anhydride, followed by deprotection and salt formation to obtain S-2732.

[0029] In the embodiment of the present invention, described hydrogen peroxide and trifluoroacetic anhydride and Fmoc-Arg (Alloc) 2 - The molar ratio of pPDA is (5-6):(6-7):(1-1.5).

[0030] In some embodiments, the hydrogen peroxide and trifluoroacetic anhydride and Fmoc-Arg (Alloc) 2 - The molar ratio of pPDA is 0.52:0.62:0.129.

[0031] In the embodiment of the present invention, hydrogen peroxide, trifluoroacetic anhydride and Fmoc-Arg (Alloc) 2 -The solvent of pPDA reaction is dichloromethane, and described hydrogen peroxide is the hydrogen peroxide aqueous solution that mass fraction is 90%; Desc...

Embodiment

[0054] 1. Fmoc-Glu(γ-pip)-OtBu

[0055] Fmoc-Glu-OtBu (48.0g, 112.9mmol), HOBt (22.9g, 169.6mmol), dichloromethane (200mL), DIEA (28.0mL, 169.6mmol), piperidine (13.4 mL, 135.6mmol), the gas was replaced with nitrogen three times, and the temperature was lowered to -5°C after the raw materials were dissolved. Under nitrogen protection, EDCI (32.5g, 169.6mmol) was quickly added, and reacted at -5-0°C for 1h after the addition, then naturally warmed to room temperature, and reacted for 12-16h. After the reaction was complete, 150 mL of water was added to the reaction liquid, and then 200 mL of dichloromethane was added for extraction. The obtained organic layer was successively washed with water, 10% citric acid, saturated NaHCO 3 Wash, wash with saturated salt. The organic layer was dried over anhydrous sodium sulfate and spin-dried below 30°C to obtain 52.9 g of a transparent liquid.

[0056] 2. H-Glu(γ-pip)-OtBu

[0057] The compound Fmoc-Glu(γ-pip)-OtBu (52.9 g, 107.3 m...

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

No PUM Login to View More

Abstract

The invention belongs to the field of polypeptide synthesis, and in particular relates to a preparation method of Suc-Ile-Glu(γ-Pip)-Gly-Arg-pNA·HCl. The method uses bis-allyloxycarbonyl (bis-Alloc) to protect the guanidine group of arginine, so that it is not affected by acid and alkali; p-phenylenediamine is first connected to the amino acid, and then hydrogen peroxide and trifluoroacetic anhydride to oxidize it, thereby improving the yield, safety and environmental protection of p-nitroaniline and amino acid condensation. Appropriate protecting groups are used for each amino acid, thereby improving the stability of the reaction process. The method provided by the invention has the advantages of environmental protection, safety, high yield, relatively low preparation cost and the like, and is suitable for mass preparation.

Description

technical field [0001] The invention belongs to the field of polypeptide synthesis, and in particular relates to a preparation method of Suc-Ile-Glu(γ-Pip)-Gly-Arg-pNA·HCl. Background technique [0002] Suc-Ile-Glu(γ-piperidyl)-Gly-Arg-pNA·HCl is an artificially synthesized polypeptide compound that can be hydrolyzed by activated factor Xa (factor Xa). It is referred to as S-2732 and is often used as a color base thing. The substrate can be used for quantitative detection of blood coagulation factor Xa and heparin anti-Xa activity, so it has wide applications in scientific research and clinical practice. [0003] No report on the synthesis of S-2732 has been found in the existing literature, and it can be found that connecting the chromophore p-nitroaniline to the amino acid is one of the key points in the synthesis of S-2732 by consulting other related synthesis literature. This is because the nitro group on p-nitroaniline has a strong electron-withdrawing effect, resulti...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07K5/103C07K1/06
CPCC07K5/101Y02P20/55
Inventor 谢永华
Owner SHANGHAI SUNBIO TECH
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com