Method of producing DL-tyrosine -**N

A technology of tyrosine and -15N, applied in organic chemistry, radioactive carrier, etc., to achieve the effect of simple device, concise method and high yield

Inactive Publication Date: 2008-04-02
SHANGHAI RES INST OF CHEM IND
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  • Summary
  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0003] Above synthetic method, there is no comparatively suitable preparation DL-tyrosine- 15 N appr

Method used

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Examples

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preparation example Construction

[0026] The present invention DL-tyrosine- 15 The analytical method adopted in the preparation process of N:

[0027] Product's 15 The abundance of N was detected by Delta S gas isotope mass spectrometer (Finnigan Company) for analysis. Adopt Waters 2487 high performance liquid chromatography (HPLC) to carry out qualitative and semiquantitative analysis to raw material, product, when sample is DL-tyrosine- 15 When N, the detection condition is: C-18 reverse phase column, mobile phase is KH 2 PO 4 (0.02mol / L, H 2 O): acetonitrile=95:5, flow velocity is 0.5ml / min, Waters 2487 ultraviolet detector, detection wavelength is 210nm, and column temperature is 30 ℃; When sample is diethyl oximinomalonate- 15 N and diethyl amidomalonate- 15N, the mobile phase is CH 3 OH:H 2 O=1:1, the flow rate is 1ml / min, the detection wavelength is 230nm, and other conditions are the same as above. The purity of the samples was tested by nitrogen determination. Use Magna-IR-550 type infrared ...

Embodiment 1

[0029] (1) diethyl oximinomalonate- 15 Synthesis of N:

[0030] 0.15mol Na 15 NO 2 (the abundance is 99.3%), 0.3mol diethyl malonate, 80ml toluene and 10g water were added in a 500ml three-necked flask and stirred evenly, the temperature of the reaction system was lowered to 0°C, and added dropwise within about 1 hour 1mol acetic acid; the temperature was raised to 30°C, and stirring was continued for 10 hours. Add toluene and water after completion of the reaction, obtain diethyl malonate-containing oximino through extraction and separation 15 The toluene phase of N is washed and dried and the toluene is removed by distillation under reduced pressure to obtain diethyl oximinomalonate- 15 N, the productive rate is 89.8% (according to Na 15 NO 2 ), the HPLC spectrum is a single peak, and the melting point is 85.6-87.8°C, which is close to the literature value of 87-88°C.

[0031] (2) Diethyl acetamidomalonate- 15 Synthesis of N:

[0032] Diethyl oximinomalonate- 15 N,...

Embodiment 2

[0038] In embodiment 1 step (1), Na 15 NO 2 The amount of , toluene, water and acetic acid was changed to 1.5mol, 40ml, 4g and 0.5mol respectively, the temperature of the increase was changed to 60°C, and the reaction time was 3 hours. ethyl ester- 15 N, the productive rate is 88.5% (according to Na 15 NO 2 meter), the HPLC spectrum is a single peak.

[0039] In embodiment 1 step (2), the amount of acetic acid and acetic anhydride is respectively changed into 2mol and 2mol, reducing agent adopts iron powder, temperature of reaction and reaction time are changed into 60 ℃ and 8 hours respectively, all the other are identical with embodiment 1, Diethyl acetamidomalonate is obtained - 15 N, the yield was 87.8%, and the HPLC spectrum was a single peak.

[0040] In step (3) of Example 1, 0.8mol of p-methoxybenzyl bromide; the temperature and time were changed to 20°C and 8 hours; the rest were the same as in Example 1 to obtain 2-acetamido-2-(p-methoxy Benzyl) diethyl malona...

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Abstract

The present invention relates to a preparation method of DL-tyrosine-15 N; the Na15NO2 is used as nitrogen isotope to synthesize DL-tyrosine-15N. The method comprises: (1) the synthesis of) oximide malonic ester diethyl oximinomalonate-15N; (2) the synthesis of acetylamino malonic ester -15N; (3) the synthesis of 2-acetyl-2-(p-methoxybenzyl) malonic ester (p-p) Diethyl - 15; (4) the synthesis of DL-tyrosine- SUP>15N; and (5) the purification of DL-tyrosine- SUP>15N. compared with the prior art, the present invention is simple in method, simple in device, high in utilization rate of raw materials, high in collection rate of product D-tyrosine-15 N, high in chemical purity and of no decrease in abundance.

Description

technical field [0001] The present invention relates to the preparation method of the organic compound of stable isotope label, relate in particular to 15 Synthetic method of N-labeled DL-tyrosine. Background technique [0002] 15 N is a stable isotope of nitrogen, 15 N markers can be used as tracers and are widely used in biochemistry, medicine, pharmacy, agricultural science and other fields, especially for life science research. DL-tyrosine- 15 N can be used as a tracer to study the metabolism in vivo, and it plays an irreplaceable role in the metabolism of drugs in the body. Organically synthesized DL-tyrosine- 15 N, there is no report in China at present. Knoop, F and Oesterlin, H (Z.Physiol.Chem., 1927, 170: 186) reported that p-hydroxyphenylpyruvate is catalyst in Pd / C, 15 Reaction under the action of N-ammonia and hydrogen to prepare DL-tyrosine- 15 N. The raw material p-hydroxyphenylpyruvate of this method is difficult to synthesize because of instability, ...

Claims

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Application Information

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IPC IPC(8): C07C229/36A61K51/04A61K101/00
Inventor 徐建飞卢伟京杜晓宁李良君
Owner SHANGHAI RES INST OF CHEM IND
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