RU2189971C1 - Highly labeled with tritium - Google Patents

Abstract

FIELD: organic chemistry, hormones, radiolabeled compounds. SUBSTANCE: Invention relates to synthesis of a novel highly labeled analog of physiologically active compound O-(4-hydroxy-3,5-diiodophenyl)-3',5'-diiodo-L-tyrosine ("thyroxine") of the formula (I)

Description

 The invention relates to the field of organic chemistry and can find application in analytical chemistry, bioorganic chemistry, biochemistry and applied medicine.

 When studying physiologically active compounds, their labeled analogues are necessary.

Данное соединение, получившее наименование "тироксин", является гормональным препаратом (E. Syniewski. //Ann./Thorac.Surg. 1993, v.56, S2-S8;
D.A. Fisher.//Clin.Chem.l996. v.42, p.135-139).Known O- (4-hydroxy-3,5-diiodophenyl) - 3 ', 5'-diiodo-L-tyrosine of the formula I:

This compound, called "thyroxine", is a hormonal drug (E. Syniewski. //Ann./Thorac.Surg. 1993, v.56, S2-S8;
DA Fisher.//Clin.Chem.l996. v. 42, p. 135-139).

 However, its tritium-labeled counterpart is not described.

 The technical result achieved by the present invention is to expand the range of labeled analogues of physiologically active compounds.

 This technical result is achieved by obtaining highly labeled with tritium O- (4-hydroxy-3,5-diiodophenyl) - 3 ', 5'-diiodo-L-tyrosine of the formula I.

 The following is an example implementation of the invention.

 Example.

20 mg of thyroxine supported on 200 mg of Lindlar catalyst were placed in a reaction vial. Then the ampoule was evacuated to a pressure of 0.1 Pa, filled with gaseous tritium to a pressure of 333 hPa and kept at a temperature of 180 ^{° C. for} 10 minutes, after which excess tritium was removed by vacuum. 5 ml of methanol was added to the ampoule, the catalyst was filtered off, the filtrate was evaporated and labile tritium was removed by evaporation three times with methanol. The residue was dissolved in 0.5 ml of methanol and the labeled preparation was isolated from the reaction mixture by HPLC. The yield of the desired labeled preparation reached 20-25%, the molar radioactivity was 6.5 Ki / mmol.

The labeled preparation was analyzed and purified by high performance liquid chromatography (HPLC) (Separon 7 μm, C ₁₈ • 150 mm, eluent speed (v) 0.5 ml / min, in a 90% methanol system — 50 mM phosphate buffer (pH 2.8 ), retention time 2.21 min; in the 70% methanol system - 10 mM phosphoric acid, retention time 19.21 min, in the 75% methanol system - 10 mM phosphoric acid, retention time 24.12 min, on a Silasorb column 15 μm , C ₁₈ , 10x250 mm, v - 1.0 ml / min, - 2.0 ml / min; in the system 85% methanol - 0.2% acetic acid - 0.015% trifluoroacetic acid, retention time 12.60 min, column Kromasil 100 _C18, 4,6h150 m; in the system 80% methanol - 10 mM phosphoric acid, v - 1,0 ml / min - 1.0 ml / min, retention time 2.48 min).

 Thus, a new physiologically active compound highly labeled with tritium was obtained.

Claims (1)

Highly labeled tritium O- (4-hydroxy-3,5-diiodophenyl) -3 ', 5'-diiodo-L-tyrosine of formula 1