Synthetic method for N(2)-L-alanyl-L-glutamine dipeptide

A glutamine dipeptide and synthesis method technology, which is applied in the field of amino acid-containing dipeptide synthesis, can solve the problems of high temperature, many side reactions, and high price, and achieve the effects of low cost, reasonable production process, and short synthetic route

Inactive Publication Date: 2005-10-19
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

(document Kunimi Inou, Yoshiyuki Yamada, US 5,380,934, Jan 10, 1995) the raw material of this reaction is chiral reagent, and price is higher, and in the step of synthesizing acid chloride, temperature is higher, and side reaction is more

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1: Dissolve 20mmol of triphosgene in 10mL of dichloromethane and add dropwise to the mixed system of 10mmol of N-(O,O-dimethyl)phosphorylalanine, 20mmol of triphenylphosphine, and 20mL of dichloromethane Inside, after reacting at -5°C for 3h, add dropwise to water containing 20mmol glutamine and 20mL, adjust the pH to 10 with potassium hydroxide during the reaction, and the reaction temperature is 0°C, react for 1.5h after dropping, and then use concentrated hydrochloric acid Acidification to pH 2.5, extraction to obtain N(2)-L-alanyl-L-glutamine dipeptide containing protective groups, the intermediate was reacted with hydrogen chloride / glacial acetic acid at room temperature for 20 h, after the reaction was completed, 50 mL of diethyl ether was added, A solid was precipitated, and the solid was recrystallized from isopropanol-water to obtain the product N(2)-L-alanyl-L-glutamine dipeptide. Yield 45%.

Embodiment 2

[0033]Example 2: 10mmol of triphenylphosphine was dissolved in 30mL of tetrahydrofuran, and added dropwise to a mixed system of 10mmol of N-(O, O-diethyl)phosphorylalanine, 15mmol of triphosgene, and 10mL of tetrahydrofuran, at 10 After reacting at ℃ for 1 hour, add it dropwise to water containing 10 mmol glutamine and 20 mL, adjust the pH to 9 with sodium hydroxide during the reaction, and the reaction temperature is 10 ℃, and react for 30 minutes after dropping. Then acidify with dilute nitric acid to pH 1.5, and extract N(2)-L-alanyl-L-glutamine dipeptide containing protective groups. The intermediate is reacted with hydrogen bromide / glacial acetic acid at room temperature for 15h, and the reaction After the completion, 50 mL of ether was added to precipitate a solid, which was recrystallized from methanol-water to obtain the product N(2)-L-alanyl-L-glutamine dipeptide. Yield 40%.

Embodiment 3

[0034] Example 3: Dissolve 15 mmol of triphosgene in 20 mL of toluene, and add dropwise to 10 mmol of N-(O, O-diisopropyl)phosphorylalanine and 15 mmol of triphenylphosphine in 20 mL of toluene at 5°C. After reacting at 5°C for 2 hours, add dropwise to a mixture containing 20mmol glutamine, 20mL water, and 5mL ethanol. During the reaction, potassium carbonate is used to adjust the pH to 9.5, and the reaction temperature is 5°C. After dropping, react for 10min. Then acidify with sulfuric acid to pH 1.0, and extract to obtain N(2)-L-alanyl-L-glutamine dipeptide containing protective groups. The intermediate is reacted with trifluoroacetic acid at room temperature for 10 h, and diethyl ether is added after the reaction 50 mL, the same body was precipitated, and the solid was recrystallized from ethanol-water to obtain the product N(2)-L-alanyl-L-glutamine dipeptide. Yield 50%.

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Abstract

The present invention relates to synthesis of dipeptide containing amino acid, and provides a kind of synthesis process of N(2)-L-alanyl-L-glutamine dipeptide with low material cost, simplicity, high yield, no need of separating and purifying intermediate product, easy product separation and purification and environment friendship. The synthesis process includes the reaction of amino acid with protected N-terminal with phosphorus triphenyl oxide and triphosgene in organic solvent to form active ester; the reaction of the active ester with glutamine in water solution of inorganic alkali; acidifying with inorganic acid and eliminating N-terminal protecting radical.

Description

technical field [0001] The invention relates to a method for synthesizing dipeptides containing amino acids, in particular to a method for synthesizing N(2)-L-alanyl-L-glutamine dipeptides. Background technique [0002] Glutamine is the most abundant amino acid in the human body, and the content of glutamine in muscle protein and plasma protein is about 75% and 26%, respectively. [0003] Glutamine has important physiological functions. Glutamine is an essential precursor of nucleic acid biosynthesis, a regulator of protein synthesis and decomposition, a carrier of amino nitrogen transfer from peripheral tissues to internal organs, and an important substrate for kidney excretion of ammonia. Glutamine is an important energy substance for intestinal mucosal epithelial cells, renal tubular cells, macrophages and fibroblasts. play an extremely important role. [0004] There are seven kinds of existing N(2)-L-alanyl-L-glutamine dipeptide synthesis methods as follows: [0005]...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/06
Inventor 唐果赵玉芬许鹏翔
Owner XIAMEN UNIV
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