ethyl (2R)-2-amino-3-sulfanylpropanoate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1.3 g of sulfodehydroabietic acid is dissolved in 15 ml of ethanol and 0.472 mg of silver carbonate and 20 ml of water are added thereto. 0.635 g of ethyl L-cysteinate hydrochloride are added to the mixture and said mixture is stirred at room temperature. The precipitates are filtered off and the filtrate is concentrated to dryness under reduced pressure. The residue is recrystallized from a mixture of methanol and ethyl acetate, whereby 1.5 g of sulfodehydroabietic acid ethyl L-cysteinate salt hemihydrate is obtained. The precipitates are filtered off the filtrate is concentrated to dryness under reduced pressure The residue is recrystallized from a mixture of methanol and ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The procedure of M. Schubert (J. Biol. Chem., 114, 341 (1936)) was used to prepare 57 starting from L-cysteine ethyl ester and salicylaldehyde. Purification by silica gel chromatography afforded 57 as a thick oil. TLC (silica gel; 3:1 cyclohexane-EtOAc) showed a mixture of 2 isomers, Rf=0.4, 0.5. IR (film): 3300 (sharp), 3000, 1740, 1430 cm-1. NMR (CCl4): 1.28 (3H, t, J=7); 2.9-3.5 (2H, m); 3.8-4.4 (3H, m); 5.50, 5.80 (1H, 2x broad s); 6.5-7.3 (4H, m). Purification by silica gel chromatography

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a mixture of 0.6 ml of ethanol and 0.1 ml (1 mol/l) of an aqueous HCl solution were dissolved 5 mg of SDH and 1.5 mg of PNP, followed by adding thereto a physiologically acceptable 99mTcO4− solution (0.5 ml, 50 MBq). The resulting mixture was heated at 80° C. for 20 minutes and then cooled to room temperature, after which 1 ml of sodium phosphate buffer (0.05 mol/l) was added thereto to adjust the pH to about 7.8. Subsequently, a solution of 3.0 mg of Cys in 0.50 ml of water was added, and the resulting mixture was allowed to stand at room temperature for 30 minutes. The complex finally obtained was analyzed by HTLC and HPLC. FIG. 6 shows a radiochromatogram of the complex which was obtained by development on a silica gel plate with an ethanol/chloroform/benzene (0.85/2/1.5) mixture. The radiochemical purity of the final complex was higher than 90%. The complex contained a Tc≡N group in which a PNP bidentate ligand was coordinated with the metal ion at trans conformation and a dianion Cys was coordinated with the remaining two positions through the sulfur atom which had lost a proton and the nitrogen atom of the amino group which had lost a proton. As a result of the same experiment as above except using an ester derivative (CysOEt), it was found that the carboxyl group of Cys did not participate in the coordination with the metal. CysOEt is formed by the replacement of the OH group of the carboxyl group of Cys by an ethoxy group, and the radiochemical purity of a final complex obtained from the ligand (CysOEt) was higher than 93% (FIG. 7). Solutions of the complexes, respectively, are all stable. were dissolved 5 mg of SDH and 1.5 mg of PNP by adding cooled to room temperature The complex finally obtained As a result of the same experiment as above

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1.3 g of sulfodehydroabietic acid is dissolved in 15 ml of ethanol and 0.472 mg of silver carbonate and 20 ml of water are added thereto. 0.635 g of ethyl L-cysteinate hydrochloride are added to the mixture and said mixture is stirred at room temperature. The precipitates are filtered off and the filtrate is concentrated to dryness under reduced pressure. The residue is recrystallized from a mixture of methanol and ethyl acetate, whereby 1.5 g of sulfodehydroabietic acid ethyl L-cysteinate salt hemihydrate is obtained. The precipitates are filtered off the filtrate is concentrated to dryness under reduced pressure The residue is recrystallized from a mixture of methanol and ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cysteine ethyl ester hydrochloride (11.2 g, 0.06 mole) was suspended in 40 ml of triethylamine with vigorous stirring for one hour at room temperature. The triethylamine hydrochloride was filtered and filtrate was concentrated to give cysteine ethyl ester as an oil. The oil was dissolved in 30 ml of pyridine and allowed to react with 3.2 g (0.01 mole) of progesterone at room temperature for 3.5 days. The suspension that resulted was filtered and crystallized from ethyl acetate to give 2.7 g (mp 162°-165° C., 47% yield) of the desired product: IR(KBr) 1740 cm-1 (s) (C=O); 1H NMR (CDCl3) δ5.23 (s, 1, CH=C), 4.2 (q, J=7 Hz, 4, CH3CH2O), 4.2-3.6 (m, 2, O2CCHN), 3.50-2.65 (m, 4, CH2S), 1.55 (s, 3, CH3 --C20), 1.3 (t, J=7 Hz, 6, CH3CH2O), 1.03 (s, 3, CH3 --C10), 0.85 (s, 3, CH3 --C13), 2.6-0.6 (m, 19, CH2 and CH); 13C NMR (CDCl3) δ171.88 and 171.99 (CO2), 148.86 (C5) and 122.89 (C4); [α]24.5 D-24.3° (C=0.63, CHCl3). The triethylamine hydrochloride was filtered filtrate was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,4-Dimethoxybenzonitrile, (R)-cysteine ethyl ester and about 5 equivalents of triethylamine are refluxed in ethanol for about 6–8 hours to obtain ethyl-2-(2,4-dimethoxyphenyl)-4,5-dihydro-thiazole-4-(R)-carboxylate.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,4-Dimethoxybenzonitrile, (R)-cysteine ethyl ester and about 5 equivalents of triethylamine are refluxed in ethanol for about 6-8 hours to obtain ethyl-2-(2,4-dimethoxyphenyl)-4,5-dihydro-thiazole-4-(R)-carboxylate.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The procedure of M. Schubert (J. Biol. Chem., 114, 341 (1936)) was used to prepare 57 starting from L-cysteine ethyl ester and salicylaldehyde. Purification by silica gel chromatography afforded 57 as a thick oil. TLC (silica gel; 3:1 cyclohexane-EtOAc) showed a mixture of 2 isomers, Rf=0.4, 0.5. IR (film): 3300 (sharp), 3000, 1740, 1430 cm-1. NMR (CCl4): 1.28 (3H, t, J=7); 2.9-3.5 (2H, m); 3.8-4.4 (3H, m); 5.50, 5.80 (1H, 2x broad s); 6.5-7.3 (4H, m). Purification by silica gel chromatography

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a mixture of 0.6 ml of ethanol and 0.1 ml (1 mol/l) of an aqueous HCl solution were dissolved 5 mg of SDH and 1.5 mg of PNP, followed by adding thereto a physiologically acceptable 99mTcO4− solution (0.5 ml, 50 MBq). The resulting mixture was heated at 80° C. for 20 minutes and then cooled to room temperature, after which 1 ml of sodium phosphate buffer (0.05 mol/l) was added thereto to adjust the pH to about 7.8. Subsequently, a solution of 3.0 mg of Cys in 0.50 ml of water was added, and the resulting mixture was allowed to stand at room temperature for 30 minutes. The complex finally obtained was analyzed by HTLC and HPLC. FIG. 6 shows a radiochromatogram of the complex which was obtained by development on a silica gel plate with an ethanol/chloroform/benzene (0.85/2/1.5) mixture. The radiochemical purity of the final complex was higher than 90%. The complex contained a Tc≡N group in which a PNP bidentate ligand was coordinated with the metal ion at trans conformation and a dianion Cys was coordinated with the remaining two positions through the sulfur atom which had lost a proton and the nitrogen atom of the amino group which had lost a proton. As a result of the same experiment as above except using an ester derivative (CysOEt), it was found that the carboxyl group of Cys did not participate in the coordination with the metal. CysOEt is formed by the replacement of the OH group of the carboxyl group of Cys by an ethoxy group, and the radiochemical purity of a final complex obtained from the ligand (CysOEt) was higher than 93% (FIG. 7). Solutions of the complexes, respectively, are all stable. were dissolved 5 mg of SDH and 1.5 mg of PNP by adding cooled to room temperature The complex finally obtained As a result of the same experiment as above

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1.3 g of sulfodehydroabietic acid is dissolved in 15 ml of ethanol and 0.472 mg of silver carbonate and 20 ml of water are added thereto. 0.635 g of ethyl L-cysteinate hydrochloride are added to the mixture and said mixture is stirred at room temperature. The precipitates are filtered off and the filtrate is concentrated to dryness under reduced pressure. The residue is recrystallized from a mixture of methanol and ethyl acetate, whereby 1.5 g of sulfodehydroabietic acid ethyl L-cysteinate salt hemihydrate is obtained. The precipitates are filtered off the filtrate is concentrated to dryness under reduced pressure The residue is recrystallized from a mixture of methanol and ethyl acetate