(2E,4E)-dodeca-2,4-dienoic acid

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

実験手順: To trans-2-decenal (5.0 g) dissolved in methylene chloride (80 ml) was added (carbomethoxymethylene)triphenylphosphorane (11.99 g), and the mixture was stirred for 2 hours. The reaction mixture was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 100:1 to 20:1) to give the methyl ester of trans,trans-2,4-dodecadienoic acid (6.1 g). Potassium hydroxide (8.1 g) was dissolved in a mixed solvent of ethanol-water (1:1) (100 ml). The methyl ester of trans,trans-2,4-dodecadienoic acid (6.1 g) was added to the mixture, and the resulting mixture was stirred at 60° C. for 40 minutes. After the reaction mixture was cooled, it was adjusted to the weak acidic range of pH with citric acid and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated to give trans,trans-2,4-dodecadienoic acid (5.4 g). To trans,trans-2,4-dodecadienoic acid dissolved in N,N-dimethylformamide (DMF, 50 ml) were added para-nitrophenol (3.8 g) and N,N'-dicyclohexylcarbodiimide (5.8 g), and the mixture was stirred for 12 hours. After precipitates obtained were removed by filtration and the solvent (DMF) was removed by distillation, the residue was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 200:1 to 50:1) to give the active ester of trans,trans-2,4-dodecadienoic acid (3.4 g). To the active ester (800 mg) dissolved in DMF (30 ml) were added 6-(4'-N-glycyl-spicaminyl-amino)purine hydrochloride (800 mg) and triethylamine (2.0 ml). The mixture was stirred for 12 hours. After the solvent was removed by distillation, the residue was subjected to chromatography on a silica gel column with eluent systems of chloroform-methanol (from 7:1 to 5:1) to give SPK282 in the yield of 310 mg.

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

実験手順: To trans-2-decenal (5.0 g) dissolved in methylene chloride (80 ml) was added (carbomethoxymethylene)triphenylphosphorane (11.99 g), and the mixture was stirred for 2 hours. The reaction mixture was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 100:1 to 20:1) to give the methyl ester of trans,trans-2,4-dodecadienoic acid (6.1 g). Potassium hydroxide (8.1 g) was dissolved in a mixed solvent of ethanol-water (1:1) (100 ml). The methyl ester of trans,trans-2,4-dodecadienoic acid (6.1 g) was added to the mixture, and the resulting mixture was stirred at 60° C. for 40 minutes. After the reaction mixture was cooled, it was adjusted to the weak acidic range of pH with citric acid and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated to give trans,trans-2,4-dodecadienoic acid (5.4 g). To trans,trans-2,4-dodecadienoic acid dissolved in N,N-dimethylformamide (DMF, 50 ml) were added para-nitrophenol (3.8 g) and N,N'-dicyclohexylcarbodiimide (5.8 g), and the mixture was stirred for 12 hours. After precipitates obtained were removed by filtration and the solvent (DMF) was removed by distillation, the residue was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 200:1 to 50:1) to give the active ester of trans,trans-2,4-dodecadienoic acid (3.4 g). To the active ester (800 mg) dissolved in DMF (30 ml) were added 6-(4'-N-glycyl-spicaminyl-amino)purine hydrochloride (800 mg) and triethylamine (2.0 ml). The mixture was stirred for 12 hours. After the solvent was removed by distillation, the residue was subjected to chromatography on a silica gel column with eluent systems of chloroform-methanol (from 7:1 to 5:1) to give SPK282 in the yield of 310 mg.

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

実験手順: To trans-2-decenal (5.0 g) dissolved in methylene chloride (80 ml) was added (carbomethoxymethylene)triphenylphosphorane (11.99 g), and the mixture was stirred for 2 hours. The reaction mixture was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 100:1 to 20:1) to give the methyl ester of trans,trans-2,4-dodecadienoic acid (6.1 g). Potassium hydroxide (8.1 g) was dissolved in a mixed solvent of ethanol-water (1:1) (100 ml). The methyl ester of trans,trans-2,4-dodecadienoic acid (6.1 g) was added to the mixture, and the resulting mixture was stirred at 60° C. for 40 minutes. After the reaction mixture was cooled, it was adjusted to the weak acidic range of pH with citric acid and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated to give trans,trans-2,4-dodecadienoic acid (5.4 g). To trans,trans-2,4-dodecadienoic acid dissolved in N,N-dimethylformamide (DMF, 50 ml) were added para-nitrophenol (3.8 g) and N,N'-dicyclohexylcarbodiimide (5.8 g), and the mixture was stirred for 12 hours. After precipitates obtained were removed by filtration and the solvent (DMF) was removed by distillation, the residue was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 200:1 to 50:1) to give the active ester of trans,trans-2,4-dodecadienoic acid (3.4 g). To the active ester (800 mg) dissolved in DMF (30 ml) were added 6-(4'-N-glycyl-spicaminyl-amino)purine hydrochloride (800 mg) and triethylamine (2.0 ml). The mixture was stirred for 12 hours. After the solvent was removed by distillation, the residue was subjected to chromatography on a silica gel column with eluent systems of chloroform-methanol (from 7:1 to 5:1) to give SPK282 in the yield of 310 mg.

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

実験手順: To trans-2-decenal (5.0 g) dissolved in methylene chloride (80 ml) was added (carbomethoxymethylene)-triphenylphosphorane (11.99 g), and the mixture was stirred for 2 hours. The reaction mixture was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 100:1 to 20:1) to give the methyl ester of trans,trans-2,4-dodecadienoic acid (6.1 g). Potassium hydroxide (8.1 g) was dissolved in a mixed solvent of ethanol-water (1:1) (100 ml). The methyl ester of trans,trans-2,4-dodecadienoic acid (6.1 g) was added to the mixture, and the resulting mixture was stirred at 60° C. for 40 minutes. After the reaction mixture was cooled, it was adjusted to the weak acidic range of pH with citric acid and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated to give trans,trans-2,4-dodecadienoic acid (5.4 g). To trans,trans-2,4-dodecadienoic acid dissolved in N,N-dimethylformamide (DMF, 50 ml) were added para-nitrophenol (3.8 g) and N,N'-dicyclohexylcarbodiimide (5.8 g), and the mixture was stirred for 12 hours. After precipitates obtained were removed by filtration and the solvent (DMF) was removed by distillation, the residue was subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 200:1 to 50:1) to give the active ester of trans,trans-2,4-dodecadienoic acid (3.4 g). To the active ester (800 mg) dissolved in DMF (30 ml) were added 6-(4'-N-glycyl-spicaminyl-amino)purine hydrochloride (800 mg) and triethylamine (2.0 ml). The mixture was stirred for 12 hours. After the solvent was removed by distillation, the residue was subjected to chromatography on a silica gel column with eluent systems of chloroform-methanol (from 7:1 to 5:1) to give SPK282 in the yield of 310 mg.

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

実験手順: (2E,4E)-dodeca-2,4-dienoic acid (2.5 g) was dissolved in dichloromethane (25 ml). Oxalyl chloride (2.23 ml) was added and the reaction mixture was stirred at room temperature for 3 h. Solvent and excess oxalyl chloride were removed, and the residue was stripped several times with DCM. The crude acid chloride was used as such in next step. Solvent and excess oxalyl chloride were removed

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl (2E,4E)-dodeca-2,4-dienoate (11.84 g) was dissolved in methanol (130 ml) and 2M aqueous sodium hydroxide solution (35 ml) was added. The reaction mixture was heated to 60° C. until full conversion was observed. After cooling down to room temperature the mixture was acidified with diluted aqueous HCl. The reaction mixture was extracted with ethyl acetate and the organic layer was washed with brine, dried over sodium sulfate, and solvents were evaporated. The crude product was used for the next step without further purification. After cooling down to room temperature the mixture The reaction mixture was extracted with ethyl acetate the organic layer was washed with brine dried over sodium sulfate, and solvents were evaporated The crude product was used for the next step without further purification