Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Production method for cyclic dipeptide

A production method and cyclic dipeptide technology, which is applied in the field of synthesis of natural compounds, can solve the problems of CHP efficacy weakening, disappearance, slow reaction rate, etc., and achieve the effect of inhibiting racemization reaction, easy to master, and simple operation

Active Publication Date: 2015-03-25
JILIN AGRICULTURAL UNIV
View PDF2 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The invention provides a production method of cyclic dipeptide to solve the problem that the reaction rate in the current methanol reflux method is very slow, and it will cause various degrees of racemization, so that the efficacy of CHP is weakened or even disappeared.

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
  • Production method for cyclic dipeptide
  • Production method for cyclic dipeptide
  • Production method for cyclic dipeptide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] (1) Low temperature protection of amino acid amino group

[0029] Using L-histidine as raw material, dissolve it in water-tetrahydrofuran (v / v=1:2) solvent, the concentration of L-histidine is 0.25mol / L, di-tert-butyl dicarbonate [( Boc) 2 O] carry out amino protection for protecting agent, first prepare tetrahydrofuran-(Boc) 2 O solution, where (Boc) 2 The concentration of O is 1mol / L, add to the alkali aqueous solution of pH 8 containing L-histidine, His: (Boc) 2 O(mol / mol)=1:2, Stir the reaction at -5°C for 15min, the stirring rate is 80r / min, then raise the temperature to 30°C and stir the reaction for 4h, after the reaction is completed, the temperature is 38°C and the vacuum degree is -0.1MPa. The organic solvent was removed under reduced pressure, the residue was dissolved in water at a ratio of 1:18 (g / mL), washed twice with ether, and the water phase / ether phase (v / v)=2:1 during each washing, to remove the residual (Boc) 2 O, then adjusted to pH 3 with 50%...

Embodiment 2

[0039] (1) Low temperature protection of amino acid amino group

[0040] Using L-histidine as raw material, dissolve it in water-tetrahydrofuran (v / v=1:2) solvent, the concentration of L-histidine is 0.50mol / L, and di-tert-butyl dicarbonate [( Boc) 2 O] carry out amino protection for protecting agent, first prepare tetrahydrofuran-(Boc) 2 O solution, where (Boc) 2 The concentration of O is 1.5mol / L, added to the alkaline aqueous solution of pH 9 containing L-histidine, His: (Boc) 2 O(mol / mol)=1:2.5, stir the reaction at -10°C for 30min, the stirring rate is 100r / min, then raise the temperature to 40°C and stir the reaction for 6h, after the reaction is completed, the temperature is 38°C and the vacuum degree is -0.1MPa. The organic solvent was removed under reduced pressure, and the residue was dissolved in water at a ratio of 1:20 (g / mL), washed with ether three times, and the water phase / ether phase (v / v)=2:1 during each washing, to remove the residual (Boc) 2 O, and th...

Embodiment 3

[0050] (1) Low temperature protection of amino acid amino group

[0051] Using L-histidine as raw material, dissolve it in water-tetrahydrofuran (v / v=1:2) solvent, the concentration of L-histidine is 0.38mol / L, and di-tert-butyl dicarbonate [( Boc) 2 O] carry out amino protection for protecting agent, first prepare tetrahydrofuran-(Boc) 2 O solution, where (Boc) 2 The concentration of O is 1.25mol / L, added to the alkaline aqueous solution of pH 8.5 containing L-histidine, His: (Boc) 2 O(mol / mol)=1:2.2. Stir the reaction at -8°C for 25min, the stirring rate is 90r / min, then raise the temperature to 35°C and stir the reaction for 5h. After the reaction, remove the organic solvent under reduced pressure at a temperature of 38°C and a vacuum of -0.1MPa, and the residue 1: 19 (g / mL) ratio was added to dissolve in water, washed 3 times with ether, water phase / ether phase (v / v) = 2: 1 during each wash, to remove residual (Boc) 2 O, then adjusted to pH 3.5 with 50% citric acid so...

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 relates to a production method for cyclic dipeptide, and belongs to a natural compound synthesis technology. Cyclic (histidine-proline) dipeptide is prepared by a cooling varying-temperature synthesis and high-pressure high-temperature water phase cyclizing technology. The production method comprises the following steps: taking hydrochloride of histidine proline dipeptide methyl ester as a raw material, and synthesizing high-quality and high-purity cyclic histidine-proline dipeptide by a high-pressure high-temperature assisted method in water containing strong basic and weak acidic salt. Compared with a conventional methanol reflux method, the production method is time-saving, efficient, high in product yield and free of racemization phenomenon.

Description

technical field [0001] The invention belongs to the technical field of synthesis of natural compounds, in particular to a production method of a cyclic (histidine-proline) dipeptide. Background technique [0002] Cyclic dipeptides are a stable six-membered ring structure formed by two amino acid residues connected to each other by a pair of complementary amide bonds. Due to its intrinsic conformational constraints, cyclic dipeptides are more stable than straight-chain dipeptides, less likely to be hydrolyzed by proteases, and have a longer half-life in vivo than corresponding dipeptide molecules. In addition, the two peptide bonds in the cyclic dipeptide molecule become hydrogen bond donors and hydrogen bond acceptors, and hydrogen bonds are one of the main ways for drugs to interact with receptors, so cyclic dipeptides are very important in medicinal chemistry. important pharmacophore. [0003] Cyclo(His-Proline) dipeptide [Cyclo(His-Pro), CHP] is an endogenous cyclic dip...

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): C07D487/04
CPCC07D487/04
Inventor 张艳荣刘婷婷王大为张雁南
Owner JILIN AGRICULTURAL UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap 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