Potassium Hydroxide → 12-Oxooctadecanoic acid

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

12-Hydroxystearic acid (2 g) dissolved in a 10% methanolic hydrochloric acid solution was stirred at room temperature for 2 hours. The mixture was then concentrated and distributed into chloroform and water, and the chloroform layer was washed with a 1% aqueous sodium hydrogen carbonate solution and water, dried with anhydrous sodium sulfate and concentrated to give the methyl ester of 12-hydroxystearic acid (2.0 g). To the methyl ester of 2-hydroxystearic acid (2.0 g) dissolved in methylene chloride (50 ml) were added Celite (4 g) and pyridinium chlorochromate (6 g), and the mixture was stirred at room temperature for 24 hours. Precipitates produced were removed by filtration. The filtrate mixed with silica gel (10 g) was concentrated and eluted with n-hexane-ethyl acetate (5:1) to give the methyl ester of 12-oxo-stearic acid (1.8 g). Then, the methyl ester of -oxo-stearic acid (1.8 g) was suspended into the mixed solvent of ethanol-water (1:1), and the potassium hydroxide (1.7 g) was dissolved in the suspension. The reaction mixture was heated to a temperature of 70° C. and stirred for 30 minutes. The reaction mixture was then cooled, adjusted to acidic range of pH by adding water and an excessive amount of citric acid and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated to give 12-oxostearic acid (1.6 g). After the 12-oxostearic acid (500 mg) was dissolved in N,N-dimethylformamide (DMF), para-nitrophenol (231 mg) and N,N'-dicyclohexylcarbodiimide (343 mg) were added, and the mixture was stirred for 12 hours. The-reaction mixture was filtered, and the solvent was removed by distillation to give the active ester of 12-oxostearic acid. The active ester (438 mg) was dissolved in DMF, 6-(4'-N-glycyl-spicaminyl-amino)purine hydrochloride (400 mg) and triethylamine (2.0 ml) were added to the solution. 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 SPK102 in the yield of 143 mg.

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