Thyroxine Methyl Ester

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

実験手順: To the aforesaid Boc-Gly-OSu solution the thyroxine methyl ester solution was added while ice cooling. After permitting the same to warm to room temperature, the mixture was stirred for 1.5 hr. After letting the reaction mixture stand overnight, 25 ml. of distilled water and 50 ml. of ethyl acetate were added thereto and the mixture was extracted with ethyl acetate. The extraction was repeated three times using 25 ml. of ethyl acetate. The ethyl acetate layers were combined and dried over anhydrous magnesium sulfate. The liquid was concentrated using a rotary evaporator and subjected to gel chromatography using a column filled with Sephadex LH-20 (made by Pharmacia Co., Ltd.). As the solvent, a mixture obtained by mixing acetone and methanol in a proportion of 4:1 (volume) was used. While confirming by TLC, the objective fraction was taken and concentrated under reduced pressure followed by crystallization. The product was obtained in an amount of 950 mg. (yield 82.5%). stand overnight the mixture was extracted with ethyl acetate The extraction dried over anhydrous magnesium sulfate The liquid was concentrated a rotary evaporator filled with Sephadex LH-20 (made by Pharmacia Co., Ltd.) As the solvent, a mixture obtained concentrated under reduced pressure followed by crystallization The product was obtained in an amount of 950 mg

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

実験手順: To the aforesaid Boc-Gly-OSu solution the thyroxine methyl ester solution was added while ice cooling. After permitting the same to warm to room temperature, the mixture was stirred for 1.5 hr. After letting the reaction mixture stand overnight, 25 ml. of distilled water and 50 ml. of ethyl acetate were added thereto and the mixture was extracted with ethyl acetate. The extraction was repeated three times using 25 ml. of ethyl acetate. The ethyl acetate layers were combined and dried over anhydrous magnesium sulfate. The liquid was concentrated using a rotary evaporator and subjected to gel chromatography using a column filled with Sephadex LH-20 (made by Pharmacia Co., Ltd.). As the solvent, a mixture obtained by mixing acetone and methanol in a proportion of 4:1 (volume) was used. While confirming by TLC, the objective fraction was taken and concentrated under reduced pressure followed by crystallization. The product was obtained in an amount of 950 mg. (yield 82.5%). stand overnight the mixture was extracted with ethyl acetate The extraction dried over anhydrous magnesium sulfate The liquid was concentrated a rotary evaporator filled with Sephadex LH-20 (made by Pharmacia Co., Ltd.) As the solvent, a mixture obtained concentrated under reduced pressure followed by crystallization The product was obtained in an amount of 950 mg

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

実験手順: To the Boc-Gly-OSu solution was added under ice-cooling the thyroxine methyl ester solution. The resulting mixture was allowed to stand to reach room temperature, and then stirred for 1.5 hrs. The reaction liquid was allowed to stand overnight, and to this were added 25 ml. of distilled water and 50 ml. of ethyl acetate for extraction with the ethyl acetate. The extraction with 25 ml. of ethyl acetate was repeated three times. The ethyl acetate extracts were combined and dried over anhydrous magnesium sulfate. The dry extract was concentrated in a rotary evaporator and subjected to gel chromatography using a column filled with Sephadex LH-20 (tradename of Pharmacia Corp.). In this procedure, a mixture of acetone and methanol in a volume ratio of 4:1 was employed as the developing solvent. Under confirmation by TLC, the fractions containing the desired product were collected and concentrated under reduced pressure to obtain a crystalline product. There was obtained 950 mg. (yield 82.5%) of the desired product. to reach room temperature The reaction liquid to stand overnight to this were added 25 ml of ethyl acetate for extraction with the ethyl acetate The extraction with 25 ml dried over anhydrous magnesium sulfate The dry extract was concentrated in a rotary evaporator filled with Sephadex In this procedure, a mixture of acetone and methanol in a volume ratio of 4:1 Under confirmation by TLC, the fractions containing the desired product were collected concentrated under reduced pressure to obtain a crystalline product There was obtained 950 mg

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

実験手順: To the Boc-Gly-OSu solution was added under ice-cooling the thyroxine methyl ester solution. The resulting mixture was allowed to stand to reach room temperature, and then stirred for 1.5 hrs. The reaction liquid was allowed to stand overnight, and to this were added 25 ml. of distilled water and 50 ml. of ethyl acetate for extraction with the ethyl acetate. The extraction with 25 ml. of ethyl acetate was repeated three times. The ethyl acetate extracts were combined and dried over anhydrous magnesium sulfate. The dry extract was concentrated in a rotary evaporator and subjected to gel chromatography using a column filled with Sephadex LH-20 (tradename of Pharmacia Corp.). In this procedure, a mixture of acetone and methanol in a volume ratio of 4:1 was employed as the developing solvent. Under confirmation by TLC, the fractions containing the desired product were collected and concentrated under reduced pressure to obtain a crystalline product. There was obtained 950 mg. (yield 82.5%) of the desired product. to reach room temperature The reaction liquid to stand overnight to this were added 25 ml of ethyl acetate for extraction with the ethyl acetate The extraction with 25 ml dried over anhydrous magnesium sulfate The dry extract was concentrated in a rotary evaporator filled with Sephadex In this procedure, a mixture of acetone and methanol in a volume ratio of 4:1 Under confirmation by TLC, the fractions containing the desired product were collected concentrated under reduced pressure to obtain a crystalline product There was obtained 950 mg

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

実験手順: To the aforesaid Boc-Gly-OSu solution the thyroxine methyl ester solution was added while ice cooling. After permitting the same to warm to room temperature, the mixture was stirred for 1.5 hr. After letting the reaction mixture stand overnight, 25 ml. of distilled water and 50 ml. of ethyl acetate were added thereto and the mixture was extracted with ethyl acetate. The extraction was repeated three times using 25 ml. of ethyl acetate. The ethyl acetate layers were combined and dried over anhydrous magnesium sulfate. The liquid was concentrated using a rotary evaporator and subjected to gel chromatography using a column filled with Sephadex LH-20 (made by Pharmacia Co., Ltd.). As the solvent, a mixture obtained by mixing acetone and methanol in a proportion of 4:1 (volume) was used. While confirming by TLC, the objective fraction was taken and concentrated under reduced pressure followed by crystallization. The product was obtained in an amount of 950 mg. (yield 82.5%). stand overnight the mixture was extracted with ethyl acetate The extraction dried over anhydrous magnesium sulfate The liquid was concentrated a rotary evaporator filled with Sephadex LH-20 (made by Pharmacia Co., Ltd.) As the solvent, a mixture obtained concentrated under reduced pressure followed by crystallization The product was obtained in an amount of 950 mg

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

実験手順: Thyroxine methyl ester (5 g), as prepared above, N-carbobenzoxyglycylglycine (1.67 g) and cyclohexylmorpholinoethylcarbodiimide (5.3 g) were combined in 40 ml of dimethylacetamide. The mixture was stirred at room temperature for 24 hours, poured into deionized water, and the resulting residue collected and washed with water. The residue was recrystallized from methanol and water, yielding the product, N-carbobenzoxyglycylglycylthyroxine methyl ester. the resulting residue collected washed with water The residue was recrystallized from methanol and water

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

実験手順: Thyroxine methyl ester (5 g), as prepared above, N-carbobenzoxyglycylglycine (1.67 g) and cyclohexylmorpholinoethylcarbodiimide (5.3 g) were combined in 40 ml of dimethylacetamide. The mixture was stirred at room temperature for 24 hours, poured into deionized water, and the resulting residue collected and washed with water. The residue was recrystallized from methanol and water, yielding the product, N-carbobenzoxyglycylglycylthyroxine methyl ester. the resulting residue collected washed with water The residue was recrystallized from methanol and water

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

実験手順: Thyroxine methyl ester (5 g), as prepared above, N-carbobenzoxyglycylglycine (1.67 g) and cyclohexylmorpholinoethylcarbodiimide (5.3 g) were combined in 40 ml of dimethylacetamide. The mixture was stirred at room temperature for 24 hours, poured into deionized water, and the resulting residue collected and washed with water. The residue was recrystallized from methanol and water, yielding the product, N-carbobenzoxyglycylglycylthyroxine methyl ester. the resulting residue collected washed with water The residue was recrystallized from methanol and water

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

実験手順: Thyroxine (20 g) was suspended in dry methanol (500 ml). The suspension was saturated with hydrogen chloride gas, cooled and saturated again. The crystals were collected, washed with methanol and ether, and then dried. The resulting thyroxine methyl ester hydrochloride crystals were added to 500 ml of methanol and an equimolar concentration of concentrated sodium hydroxide was added with stirring. Deionized distilled water (500 ml) was added to this solution. The solution was chilled to recrystallize the thyroxine methyl ester from the solution. The crystals were then collected and air dried. cooled The crystals were collected washed with methanol and ether dried The resulting thyroxine methyl ester hydrochloride crystals were added to 500 ml of methanol an equimolar concentration of concentrated sodium hydroxide was added Deionized distilled water (500 ml) was added to this solution The solution was chilled to recrystallize the thyroxine methyl ester from the solution The crystals were then collected air dried

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

実験手順: Thyroxine methyl ester (5 g), as prepared above, N-carbobenzoxyglycylglycine (1.67 g) and cyclohexylmorpholinoethylcarbodiimide (5.3 g) were combined in 40 ml of dimethylacetamide. The mixture was stirred at room temperature for 24 hours, poured into deionized water, and the resulting residue collected and washed with water. The residue was recrystallized from methanol and water, yielding the product, N-carbobenzoxyglycylglycylthyroxine methyl ester. the resulting residue collected washed with water The residue was recrystallized from methanol and water

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

実験手順: Thyroxine methyl ester (5 g), as prepared above, N-carbobenzoxyglycylglycine (1.67 g) and cyclohexylmorpholinoethylcarbodiimide (5.3 g) were combined in 40 ml of dimethylacetamide. The mixture was stirred at room temperature for 24 hours, poured into deionized water, and the resulting residue collected and washed with water. The residue was recrystallized from methanol and water, yielding the product, N-carbobenzoxyglycylglycylthyroxine methyl ester. the resulting residue collected washed with water The residue was recrystallized from methanol and water

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

実験手順: Thyroxine (20 g) was suspended in dry methanol (500 ml). The suspension was saturated with hydrogen chloride gas, cooled and saturated again. The crystals were collected, washed with methanol and ether, and then dried. The resulting thyroxine methyl ester hydrochloride crystals were added to 500 ml of methanol and an equimolar concentration of concentrated sodium hydroxide was added with stirring. Deionized distilled water (500 ml) was added to this solution. The solution was chilled to recrystallize the thyroxine methyl ester from the solution. The crystals were then collected and air dried. cooled The crystals were collected washed with methanol and ether dried The resulting thyroxine methyl ester hydrochloride crystals were added to 500 ml of methanol an equimolar concentration of concentrated sodium hydroxide was added Deionized distilled water (500 ml) was added to this solution The solution was chilled to recrystallize the thyroxine methyl ester from the solution The crystals were then collected air dried