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Synthetic method of stable isotope deuterium-labeled alpha-amino acid

A technology of stable isotope and synthesis method, which is applied in the field of synthesis of stable isotope deuterium-labeled α-amino acid, can solve the problems of long reaction steps, dilution of abundance, low utilization rate of isotope atoms, etc.

Inactive Publication Date: 2018-07-20
SHANGHAI RES INST OF CHEM IND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The synthesis method of these amino acids has long reaction steps, long reaction time, and low utilization rate of isotope atoms, which is easy to cause abundance dilution

Method used

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  • Synthetic method of stable isotope deuterium-labeled alpha-amino acid
  • Synthetic method of stable isotope deuterium-labeled alpha-amino acid
  • Synthetic method of stable isotope deuterium-labeled alpha-amino acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] A stable isotope labeled alanine-D 3 The preparation method, this method comprises the following steps:

[0056] 1. Methyl substituted phthalimide dimethyl malonate-D 3 Synthesis

[0057] Add 3.98g of phthalimide dimethyl malonate sodium salt into a 50mL reaction bottle, 20mL of chloroform and stir to disperse, then add iodomethane-D 3 1.65g, the reaction temperature is 40 ℃, and the reaction time is 2 hours. After the reaction is completed, wash with water and dry to obtain 3.68g product. The yield is represented by methyl iodide-D 3 Total 84.1%, HPLC detection, purity 99.5%; mass spectrometry detection, abundance 99.5atom%D.

[0058] 2. Alanine-D 3 Synthesis

[0059] Add methyl substituted phthalimide dimethyl malonate-D in a 50mL reaction flask 31.94g, after 20mL of absolute ethanol was stirred and dissolved, 10mL of sodium hydroxide aqueous solution was added, and the reaction time was refluxed for 4 hours. The yield of base-substituted phthalimide dimethyl ...

Embodiment 2

[0061] A stable isotope labeled valine-D 6 The preparation method, this method comprises the following steps:

[0062] 1. Isopropyl substituted phthalimide dimethyl malonate-D 6 Synthesis

[0063] Add 2.00g of phthalimide dimethyl malonate sodium salt into a 50mL reaction bottle, stir and dissolve DMF20mL, then add bromoisopropane-D 6 1.55g, the reaction temperature is 100°C, and the reaction time is 5 hours. After the reaction is completed, wash with water and dry to obtain 1.70g product. The yield is represented by bromoisopropane-D 6 Total 79.1%, HPLC detection, purity 99.5%; mass spectrometry detection, abundance 99.3atom%D.

[0064] 2. Valine-D 6 Synthesis

[0065] Add isopropyl substituted phthalimide dimethyl malonate-D in a 50mL reaction flask 6 2.15g, after 20mL of anhydrous methanol was stirred and dissolved, 5mL of potassium hydroxide aqueous solution was added, and the reaction time was refluxed for 2 hours. The yield of propyl-substituted phthalimide dimet...

Embodiment 3

[0067] A stable isotope labeled leucine-D 6 The preparation method, this method comprises the following steps:

[0068] 1. Isobutyl substituted phthalimide dimethyl malonate-D 6 Synthesis

[0069] Add 6.00g of phthalimide dimethyl malonate sodium salt into a 50mL reaction bottle, stir and dissolve 15mL of DMSO, then add bromoisobutane-D 6 1.43g, the reaction temperature is 120°C, and the reaction time is 2 hours. After the reaction is completed, it is washed with water and dried to obtain 6.57g of product. The yield is represented by bromoisobutane-D 6 Total 91.3%, HPLC detection, purity 99.4%; mass spectrometry detection, abundance 99.4atom%D.

[0070] 2. Leucine-D 6 Synthesis

[0071] Add isobutyl substituted phthalimide dimethyl malonate-D in a 50mL reaction flask 6 2.40g, after stirring and dissolving in 10mL of absolute ethanol, add 15mL of potassium carbonate aqueous solution, and reflux for 6 hours. The yield of dimethyl malonate substituted with phthalimide was...

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Abstract

The invention relates to a synthetic method of stable isotope deuterium-labeled alpha-amino acid. According to the method, one or more deuterium-labeled halides are taken as labeled precursors and subjected to a reaction with phthalimide dimethyl malonate sodium salt, one or more deuterium-substituted phthalimide dimethyl malonate is obtained, and after hydrolysis, stable isotope deuterium-labeledalpha-amino acid is obtained. Compared with the prior art, the synthetic method is simple, safe and reliable, chemical purity of a product after simple separation and purification reaches 99% or higher, isotope abundance is 99% or higher, and the method can be applied to fields of protein metabolism tracing, food safety testing and the like.

Description

technical field [0001] The invention relates to a synthesis method of isotope-labeled amino acid, in particular to a synthesis method of stable isotope deuterium-labeled alpha-amino acid. Background technique [0002] Amino acid is the original unit of all living matter structures, and its constituent proteins (proteins), polypeptides (polypeptides) and enzymes (enzymes) in the body can be obtained through complex biochemical pathways through tissue structures and enzymes and other physiological units. Distribute energy so as to maintain the essential characteristics of living organisms. [0003] Deuterium is one of the stable isotopes of hydrogen, which can be used as a tracer element in biochemistry, medicine, pharmacy, agricultural science and other fields. Deuterium-labeled amino acids and peptides are important tools for research in medicine and life sciences. Based on the consistent structure, similar properties, stable and non-radioactive characteristics of deuterat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/48C07C227/20C07C229/08C07D209/20C07C229/36C07D233/64C07C319/20C07C323/58C07B59/00
CPCC07B59/001C07B59/002C07B2200/05C07C227/20C07C319/20C07D209/20C07D209/48C07D233/64C07C229/08C07C229/36C07C323/58
Inventor 徐仲杰罗勇钟佳琪涂亚辉孙雯
Owner SHANGHAI RES INST OF CHEM IND
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