Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Preparation method of hapten acetyl iodothyroxine active coupling reagent

The technology of thyroxine and coupling reagent is applied in the field of preparation of hapten acetyliodothyronine active coupling reagent, which can solve the problems such as difficulty in obtaining raw materials, poor solubility, long reaction time, etc. The effect of reducing costs and simple steps

Pending Publication Date: 2021-08-06
英科新创(苏州)生物科技有限公司
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] At present, there are few methods for synthesizing the hapten acetyliodothyronine (T4 and anti-T4, T3 and anti-T3, and T2 and anti-T2) active coupling reagents, mainly because of the following technical difficulties: acetic anhydride is useful in T4 acetylation Reaction in the solvent DMF, but the solubility of iodothyroxine (T4 and anti-T4, T3 and anti-T3 and T2 and anti-T2) in organic solvents or water is not good, resulting in a long reaction time, low yield, and many side reactions. Difficult to purify
And the acetic anhydride used in this process is a precursor chemical controlled by the state, and the raw materials are not easy to obtain

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 hapten acetyl iodothyroxine active coupling reagent
  • Preparation method of hapten acetyl iodothyroxine active coupling reagent
  • Preparation method of hapten acetyl iodothyroxine active coupling reagent

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0049] The invention discloses a preparation method of a hapten acetyliodothyronine active coupling reagent, which comprises the following steps:

[0050] S1, preparation of acetic acid active ester;

[0051] S2, reacting the prepared acetic acid active ester with iodothyroxine to synthesize intermediate compound 1;

[0052] S3, reacting the intermediate compound 1 with N-hydroxysuccinimide and a condensing agent to synthesize the hapten acetyliodothyronine active coupling reagent 2;

[0053] The synthetic reaction formula is:

[0054]

[0055] Wherein, the general formula of iodothyroxine is shown in formula A and formula B, and formula B is the trans form of formula A;

[0056] where the R 1 and R 2 The group is hydrogen or iodine; formula A includes T 4 , T 3 or T 2 ;Formula B includes anti-T 4 , Anti-T 3 and anti-T 2 ;

[0057] The specific chemical formula is as follows:

[0058]

[0059] Specifically, the specific steps for preparing acetic acid active es...

specific example 1

[0073]

[0074] The specific experimental conditions for the synthesis of intermediate compound 1 in S1 and S2 include: under nitrogen protection, acetic acid (0.7g, 3eq) and HOSU (1.3g, 3eq) were added to DMF (10ml), and EDC was slowly added below 20°C. HCl (2.2g, 3eq), react at 25°C for more than 1h. Then T4 (3g, 1eq) was added to DMF (15ml), and K 2 CO 3 (1.6g, 3eq) was added to water (20ml) to dissolve, then mixed to dissolve T4. Then add the reacted acetic acid active ester solution dropwise into the T4 solution, and react at room temperature for 1 hour. After the reaction is completed, adjust the pH to be acidic with dilute HCl aqueous solution, extract 3 times with an appropriate amount of EA, wash 2 times with saturated NaCl aqueous solution, and wash the EA solution with Anhydrous Na 2 SO 4 Dry, remove EA in a rotary evaporator, and use it directly for the next step without purification;

[0075] S3. Synthesis of product 2: Under nitrogen protection, intermedi...

specific example 2

[0077]

[0078] Synthesis of S1 and S2, intermediate compound 1: under nitrogen protection, acetic acid (0.82g, 3eq) and HOSU (1.6g, 3eq) were added to DMF (10ml), and EDC·HCl (2.65g , 3eq), react at 25°C for more than 1h. Then T3 (3g, 1eq) was added to DMF (15ml), K2CO3 (1.9g, 3eq) was added to water (20ml) to dissolve, and then mixed to dissolve T3. Then add the reacted acetic acid active ester solution dropwise into the T3 solution, and react at room temperature for more than 1 hour. After the reaction is completed, adjust the pH to be acidic with dilute HCl aqueous solution, extract 3 times with an appropriate amount of EA, wash 2 times with saturated NaCl aqueous solution, and EA solution with anhydrous Na 2 SO 4 Dry, remove EA in a rotary evaporator, and use it directly for the next step without purification;

[0079] S3. Synthesis of product 2: under nitrogen protection, compound 1 (1.5g, 1eq) and HOSU (0.3g, 1.2eq) were added to DMF (20ml), and EDC·HCl (0.5g, 1.2...

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 discloses a preparation method of a hapten acetyl iodothyroxine active coupling reagent. The preparation method comprises the following steps: preparing acetic acid active ester; subjecting the prepared acetic acid active ester to reacting with iodothyroxine to synthesize an intermediate compound 1; and subjecting the intermediate compound 1 to reacting with N-hydroxysuccinimide and a condensing agent to synthesize the hapten acetyl iodothyroxine active coupling reagent. The preparation method has the advantages of low price and easy availability of raw materials, few synthesis steps, simplicity in operation, convenience in extraction and purification and high yield, provides a brand new solution for synthesizing the hapten acetyl iodothyroxine active coupling reagent, and overcomes problems in synthesis of artificial antigen key raw materials during preparation of monoclonal antibodies from micromolecule haptens and in synthesis of key raw materials in development of kits for clinical detection of thyroid function items.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a preparation method of a hapten acetyliodothyronine active coupling reagent. Background technique [0002] At present, there are few methods for synthesizing the hapten acetyliodothyronine (T4 and anti-T4, T3 and anti-T3, and T2 and anti-T2) active coupling reagents, mainly because of the following technical difficulties: acetic anhydride is useful in T4 acetylation Reaction in the solvent DMF, but the solubility of iodothyroxine (T4 and anti-T4, T3 and anti-T3 and T2 and anti-T2) in organic solvents or water is not good, resulting in a long reaction time, low yield, and many side reactions. Purification is difficult. And the acetic anhydride used in this process is a precursor chemical controlled by the state, and the raw materials are not easy to obtain. [0003] Iodothyroxine is a hapten with a molecular mass of less than 1000u and is only reactogenic but not imm...

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 Applications(China)
IPC IPC(8): C07D207/46
CPCC07D207/46
Inventor 张冬冬
Owner 英科新创(苏州)生物科技有限公司
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
Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com