(E)-dodec-2-enal

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of trans-2-dodecenal (4.5 g) dissolved in methylene chloride (80 ml ) was added (carbomethoxymethylene)triphenylphosphorane (8.3 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-tetradecadienoic acid (5.4 g). To a solution of potassium hydroxide (6.5 g) in a mixed solvent of ethanol-water (1:1) (100 ml) was added the methyl ester of trans,trans-2,4-tetradecadienoic acid (5.4 g), and the mixture was stirred at 60° C. for 40 minutes. The reaction mixture was cooled, and acidified to a 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-tetradecadienoic acid (4.3 g). To the tetradecadienoic acid dissolved in N,N-dimethylformamide (DMF, 50 ml) was added para-nitrophenol (2.67 g) and N,N'-dicyclohexylcarbodiimide (3.9 g), and the mixture was stirred for 12 hours. After precipitates produced were removed by filtration and DMF was evaporated, 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-tetradecadienoic acid (5.1 g). To the active ester (500 mg) dissolved in DMF (30 ml) were added 6-(4'-N-glycyl-septaminyl-amino)purine hydrochloride (560 mg) and triethylamine (1.5 ml), and the mixture was stirred for 18 hours. The solvent was evaporated, and 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 SPT241 in the yield of 271 mg.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To trans-2-dodecenal (4.5 g) dissolved in methylene chloride (80 ml) was added (carbomethoxymethylene)triphenylphosphorane (8.3 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-tetradecadienoic acid (5.4 g). Potassium hydroxide (6.5 g) was dissolved in a mixed solvent of ethanol-water (1:1) (100 ml). The methyl ester of trans,trans-2,4-tetradecadienoic acid (5.4 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-tetradecadienoic acid (4.4 g). Hereafter, the title compound can be synthesized by the two methods described below.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of trans-2-dodecenal (4.5 g) dissolved in methylene chloride (80 ml) was added (carbomethoxymethylene)triphenylphosphorane (8.3 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-tetradecadienoic acid (5.4 g). To a solution of potassium hydroxide (6.5 g) in a mixed solvent of ethanol-water (1:1) (100 ml) was added the methyl ester of trans,trans-2,4-tetradecadienoic acid (5.4 g), and the mixture was stirred at 60° C. for 40 minutes. The reaction mixture was cooled, and acidified to a 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-tetradecadienoic acid (4.3 g). To the tetradecadienoic acid dissolved in N,N-dimethylformamide (DMF, 50 ml) was added para-nitrophenol (2.67 g) and N,N'-dicyclohexylcarbodiimide (3.9 g), and the mixture was stirred for 12 hours. After precipitates produced were removed by filtration and DMF was evaporated, 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-tetradecadienoic acid (5.1 g). To the active ester (500 mg) dissolved in DMF (30 ml) were added 6-(4'-N-glycyl-septaminyl-amino)purine hydrochloride (560 mg) and triethylamine (1.5 ml), and the mixture was stirred for 18 hours. The solvent was evaporated, and 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 SPT241 in the yield of 271 mg.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To trans-2-dodecenal (4.5 g) dissolved in methylene chloride (80 ml) was added (carbomethoxymethylene)-triphenylphosphorane (8.3 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-tetradecadienoic acid (5.4 g). Potassium hydroxide (6.5 g) was dissolved in a mixed solvent of ethanol-water (1:1) (100 ml). The methyl ester of trans,trans-2,4-tetradecadienoic acid (5.4 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-tetradecadienoic acid (4.4 g). Hereafter, the title compound can be synthesized by the two methods described below.