RU1649779C - Method of obtaining aminoacids traced with tritium - Google Patents

Abstract

The invention relates to labeled compounds, in particular to the production of highly tritiated a-amine acid, which are used for biomedical research. The goal is to increase the molar activity of the target product. The preparation is carried out by applying a-amino acid to a Pd / CaCO3 or Pd / C catalyst on a support followed by isotopic exchange with tritium gas at 180-240 ° C. The method allows to obtain highly labeled with tritium a-amino acids with a molar activity of 83-190 Ci / mmol against 45-60 Ku / mmol in the known method with a degree of substitution of hydrogen for tritium 73-82%, while the compounds retain their properties for 3 month 3 tab.

Description

The invention relates to the production of biologically active compounds labeled with radioactive isotopes, and in particular to an improved method for producing highly labeled with tritium a-amino acids, which are widely used for biomedical research

The aim of the invention is to increase the molar activity of the target products

Example 1 5.5 mg of a catalyst mixture containing 5% palladium on calcium carbonate and lyophilized L-valine in an amount of 0.5 mg are placed in a 10 ml isotopic exchange vial. The ampoule is evacuated to a pressure of 10 hPa and filled with gaseous tritium to a pressure of 400 hPa. The ampoule is heated at 220 ° C for 30 min.t

The reaction mixture was suspended in 3.0 ml of 0.1 M aqueous ammonia, the catalyst was separated by centrifugation, the solution was evaporated twice to dryness with 0.1 M aqueous ammonia to remove labile tritium and dissolved in 150 μl of 0.1 M aqueous ammonia.

Chromatographic purification was carried out on the Amberlit CO 50 (III) carboxylic cation exchanger in copper form. The degree of filling of the sorbent with copper ions is 70%. Eluent 0.2 M aqueous ammonia. An ultraviolet flow detector is used. A 15 x 10 mm column was used to remove traces of copper from the eluent filled with the Dauex A-1 complexing sorbent. The amino acid fraction is collected from 20 to 26 ml. The eluent was evaporated, the amino acid was dissolved in 50% aqueous ethanol and the radioactive concentration was adjusted to 1 Ci / L. 65 mCi of Nevzlin with a molar activity of 170 Ku / mmol is obtained. Chemical yield 8.9%. An analysis of radiochemical purity was carried out

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using thin-layer chromatography on Silufol in the system isopropanol, acetone, ammonia (15: 9: 9). Valim mobility 0.45; Radiochemical purity 98%. The analysis of optical purity was carried out using column ligand exchange chromatography on a chiral sorbent, optical purity 17%, degree of substitution of hydrogen for tritium 82%.

Examples 2-7. 11 mg of a mixture of catalyst containing 5% palladium on calcium carbonate and 1 mg of L-valine are placed in a 10 ml isotopic exchange vial. The ampoule is evacuated and filled with a tritium – hydrogen mixture containing 0.1% tritium to a pressure of 400 Pa.

The isotope exchange process and the isolation of the tritium-labeled roller are carried out as described in Example 1. The dependence of the inclusion of tritium on the temperature of the isotope exchange is shown in Table 1.

Examples 8-11. 11 mg of a mixture of a catalyst containing 5% palladium on calcium carbonate and 1 mg of L-amino acid are placed in a 10 ml isotopic exchange vial. The ampoule is evacuated and filled with 0.1% tritium to a pressure of 400 hPa. The reaction is carried out at 200 ° C for 30 minutes. The results of the isotope exchange reaction are shown in Table 2.

Example 12 6 mg of a mixture containing 5 mg of catalyst, 10% palladium on carbon and 2 mg of L-valine are placed in a 10 mm isotopic exchange vial. The ampoule is evacuated and filled with 0.1% tritium to

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pressure 350 hPa. The reaction was carried out at 200 ° C for 40 minutes. Isolation of the product is carried out as described in Example 1. 120 μg of valine with a molar activity of 130 Ku / mmol are obtained with a chemical yield of 12%.

In all examples, the corresponding amino acid is applied to the catalyst.

Table 3 shows comparative data using other carriers of the palladium catalyst, which show the impossibility of producing labeled amino acids with high molar activity,

Thus, the method allows to obtain highly tritiated "-amino acids with a molar activity of 83-190 Ku / mmol versus 45-60 Ku / mmol in the known method with a degree of substitution of hydrogen for 73-82% tritium.

In this case, the compounds retain their properties for 3 months.

Claims (1)

The claims A method for producing highly tritiated α-amino acids by depositing a nitrogen-containing compound on a supported palladium catalyst followed by isotopic exchange with tritium gas at 180-240 ° C, characterized in that, with the aim of increasing the molar activity of the target product, using “- amino acid, and as a catalyst, Pd / CaCOsili Pd / C. Table Table 2