3,5-dioxohexanoic acid

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

実験手順: The iodide 2 (286.6 mg) and 6-hydroxy-α-methylnaphthaleneacetic acid methyl ester (154.0 mg) were dissolved in dimethylformamide (3 ml) and potassium carbonate (277,6 mg) was added. The reaction was stirred at room temperature for 12 hours, after which it was partitioned between water (10 ml) 15 and ethyl acetate (50 ml). The layers were separated and the organics were washed with water (3×10 ml) and brine (10 ml). The organic layer was dried over magnesium sulfate, filtered and concentrated to dryness. Purification of the residue on silica gel (25% ethyl acetate/hexane) gave the desired triacetate (225.8 mg, 64% yield). after which it was partitioned between water (10 ml) 15 and ethyl acetate (50 ml) The layers were separated the organics were washed with water (3×10 ml) and brine (10 ml) The organic layer was dried over magnesium sulfate filtered concentrated to dryness Purification of the residue on silica gel (25% ethyl acetate/hexane)

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of ethyl 3,7-dihydroxy-2-naphthoate (62 mg, 0.26 mmole) (the acid was obtained from Aldrich and it was converted to the ester using standard techniques) 2 mg, and iodide 2 (242 mg) in dimethylforamide (0.5 ml) was heated at 55° C. with potassium carbonate (175 mg) for 4 hours. An additional amount of the iodide 2 (80 mg) was added to the mixture which was heated at 55° C. overnight. The mixture was worked up with water (50 ml) and ethyl acetate (2×75 ml). The ethyl acetate extracts were washed with brine (30 ml), dried over sodium sulfate, filtered and concentrated. The crude product was purified on a silica gel column (hexane:ethyl acetate, 1.5:1) to provide the triacetate of 17 (130 mg, 65% yield). The ethyl acetate extracts were washed with brine (30 ml) dried over sodium sulfate filtered concentrated The crude product was purified on a silica gel column (hexane:ethyl acetate, 1.5:1)

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

実験手順: A solution of ethyl 6-hydroxyl-2-naphthate (49, 89 mg, 0.42 mmole) (6-hydroxy-2-naphthoic acid was obtained from TCI America and converted to the ester using standard esterification methods) and iodide (2, 177 mg, 0.42 mmole) in dimethylforamide (1 ml) was stirred with potassium carbonate (174 mg) for 14 hours. The reaction mixture was worked up with water (30 ml) and ethyl acetate (100 ml). The organic layer was washed with brine (30 ml), dried over sodium sulfate, filtered and concentrated. The crude product was purified on a silica gel column (hexane ethyl acetate, 4:1) to provide the triacetate of 3 (120 mg, 55%). The organic layer was washed with brine (30 ml) dried over sodium sulfate filtered concentrated The crude product was purified on a silica gel column (hexane ethyl acetate, 4:1)

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

実験手順: Ne -benzyloxycarbonyl-L-lysine, n-stearyl alcohol, p-toluenesulfonic acid and monohydrate, and benzene are refluxed together using a Dean-Stark trap to azeotropically remove the evolved water. After cooling to room temperature and then adding dry ethyl ether, n-stearyl Ne -benzyloxycarbonyl-L-lysinate p-toluenesulfonate salt is collected by filtration, treated with 2M aqueous potassium bicarbonate solution, and extracted into dichloromethane. Evaporation gives the free amine, which is redissolved in dry tetrahydrofuran (THF) and added to a stirring solution of Na -t-butyloxycarbonyl-Nim -benzyloxycarbonyl-L-histidine, N-methylmorpholine, and isobutyl chloroformate in dry THF at -15° C. The resulting fully protected dipeptide ester is treated with 1/1 trifluoroacetic acid/dichloromethane at room temperature, neutralized with saturated aqueous sodium bicarbonate solution, and extracted into ethyl acetate. Evaporation gives the partially deblocked dipeptide, which is redissolved in dry THF and added to a stirring solution of benzyloxycarbonyl-glycine, N-methylmorpholine and isobutyl chloroformate in dry THF at -15° C. The formed, fully protected tripeptide ester is totally deblocked by treatment with hydrogen gas in glacial acetic acid at room temperature in the presence of Pd-C catalyst. Filtration, evaporation and purification on a microcrystalline cellulose column followed by lyophilization give the desired tripeptide ester as its triacetate salt. Filtration, evaporation and purification on a microcrystalline cellulose column

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

実験手順: To a mixture of 2,2,4,4-tetramethylcyclohexane-1,3,5-trione (182 mg, 1 mmol) and 4-dimethylaminopyridine (610 mg, 5 mmol) under an atmosphere of nitrogen, is added dry chloroform (5.6 ml), followed by stirring at room temperature until dissolution is complete. To this solution is then added dry toluene (2 ml), and 3,5-dimethylbiphenylead triacetate (0.5 M solution in dry chloroform, 2.4 ml, 1.2 mmol). This solution is then heated under reflux for 1 hour. The reaction mixture is cooled to room temperature, acidified to pH 1 with 2N aqueous hydrochloric acid, filtered and the filtrate is extracted with dichloromethane (2×40 ml). The organic extracts are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure. The residue is further purified by column chromatography on silica gel to give 6-(3,5-dimethylbiphenyl-4-yl)-2,2,4,4-tetramethylcyclohexane-1,3,5-trione (166 mg). This solution is then heated under reflux for 1 hour The reaction mixture is cooled to room temperature filtered the filtrate is extracted with dichloromethane (2×40 ml) dried over anhydrous magnesium sulfate filtered the filtrate is evaporated under reduced pressure The residue is further purified by column chromatography on silica gel

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

実験手順: 1 g of phlorizin, 10 mL of acetic anhydride, and 0.82 g (0.01 mol) of sodium acetate were reacted at 100° C. for 6 hrs. The reaction mixture was cooled and the triacetate derivative of phlorizin precipitated from the solution in the form of a crystalline solid. The crystalline solid was separated by filtration, dissolved in 50 mL of hot methanol, and re-crystallized twice from hot methanol. The reaction yielded 0.6 g of the triacetate. The reaction mixture was cooled the triacetate derivative of phlorizin precipitated from the solution in the form of a crystalline solid The crystalline solid was separated by filtration dissolved in 50 mL of hot methanol re-crystallized twice from hot methanol

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

実験手順: 1 g of phlorizin, 10 mL of acetic anhydride, and 0.82 g (0.01 mol) of sodium acetate were reacted at 100° C. for 6 hrs. The reaction mixture was cooled and the triacetate derivative of phlorizin precipitated from the solution in the form of a crystalline solid. The crystalline solid was separated by filtration, dissolved in 50 mL of hot methanol, and re-crystallized twice from hot methanol. The reaction yielded 0.6 g of the triacetate. The reaction mixture was cooled the triacetate derivative of phlorizin precipitated from the solution in the form of a crystalline solid The crystalline solid was separated by filtration dissolved in 50 mL of hot methanol re-crystallized twice from hot methanol

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

実験手順: N(ε)-benzyloxycarbonyl-L-lysine, n-stearyl alcohol, p-toluenesulfonic acid monohydrate, and benzene are refluxed together using a Dean-Stark trap to azeotropically remove the evolved water. After cooling to room temperature and then adding dry ethyl ether, n-stearyl N(ε)-benzyloxycarbonyl-L-lysinate p-toluenesulfonate salt is collected by filtration, treated with 2M aqueous potassium bicarbonate solution, and extracted into dichloromethane. Evaporation give the free amine, which is redisolved in dry tetrahydrofuran (THF) and added to a stirring solution of N(α)-t-butyloxycarbonyl-N(im)-benzyloxy-carbonyl-L-histidine, N-methylmorpholine, and isobutyl chloroformate in dry THF at -15° C. The resulting fully protected dipeptide ester is treated with 1/1 trifluoroacetic acid/dichloromethane at room temperature, neutralized with saturated aqueous sodium bicarbonate solution, and extracted into ethyl acetate. Evaporation gives the partially deblocked dipeptide, which is redissolved in dry THF and added to a stirring solution of benzyloxycarbonylglycine, N-methylmorpholine and isobutyl chloroformate in dry THF at -15° C. The formed, fully protected tripeptide ester is totally deblocked by treatment with hydrogen gas in glacial acetic acid at room temperature in the presence of Pd-C catalyst. Filtration, evaporation and purification on a microcrystalline cellulose column followed by lyophilization give the desired tripeptide ester as its triacetate salt. Filtration, evaporation and purification on a microcrystalline cellulose column

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

実験手順: N(ε)-benzyloxycarbonyl-L-lysine, n-stearyl alcohol, p-toluenesulfonic acid monohydrate, and benzene are refluxed together using a Dean-Stark trap to azeotropically remove the evolved water. After cooling to room temperature and then adding dry ethyl ether, n-stearyl N(ε)-benzyloxycarbonyl-L-lysinate p-toluenesulfonate salt is collected by filtration, treated with 2M aqueous potassium bicarbonate solution, and extracted into dichloromethane. Evaporation give the free amine, which is redisolved in dry tetrahydrofuran (THF) and added to a stirring solution of N(α)-t-butyloxycarbonyl-N(im)-benzyloxy-carbonyl-L-histidine, N-methylmorpholine, and isobutyl chloroformate in dry THF at -15° C. The resulting fully protected dipeptide ester is treated with 1/1 trifluoroacetic acid/dichloromethane at room temperature, neutralized with saturated aqueous sodium bicarbonate solution, and extracted into ethyl acetate. Evaporation gives the partially deblocked dipeptide, which is redissolved in dry THF and added to a stirring solution of benzyloxycarbonylglycine, N-methylmorpholine and isobutyl chloroformate in dry THF at -15° C. The formed, fully protected tripeptide ester is totally deblocked by treatment with hydrogen gas in glacial acetic acid at room temperature in the presence of Pd-C catalyst. Filtration, evaporation and purification on a microcrystalline cellulose column followed by lyophilization give the desired tripeptide ester as its triacetate salt. Filtration, evaporation and purification on a microcrystalline cellulose column

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a cooled (0° C.) solution of 38.1 mg (0.127 mmol) of D-erythro-sphingosine 1 in 3.0 mL of dichloromethane was added 61.5 μL (0.762 mmol) of pyridine, 72.0 μL (0.762 mmol) of acetic anhydride and 0.78 mg (6.4 μmol) of 4-dimethylaminopyridine. The solution was warmed to 25° C., stirred for 2 h and poured in 30 mL of dichloromethane. The mixture was washed with 40 mL each of saturated aqueous sodium bicarbonate, saturated aqueous cupric sulfate, brine and dried over anhydrous sodium sulfate. Concentration in vacuo yielded 52.3 mg (97%) of nearly pure triacetate as an off-white solid. Recrystallization from hexanes afforded 48.2 mg (89%) of pure triacetate as feathery white crystals, mp 102-103° C. A second recrystallization from diethyl ether:hexanes gave an analytical sample as feathery white crystals, mp 103.0-103.5° C. The mixture was washed with 40 mL each of saturated aqueous sodium bicarbonate, saturated aqueous cupric sulfate, brine dried over anhydrous sodium sulfate Concentration in vacuo

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

実験手順: The fully protected dipeptide formed above was deblocked by treatment with 1/2 trifluoroacetic acid/dichloromethane at room temperature, followed by neutralization with saturated aqueous potassium bicarbonate. Extraction into ethyl acetate and evaporation gave the partially deblocked dipeptide, which was added to a solution prepared from Na -benzyloxycarbonyl glycine, N-methylmorpholine, and isobutyl chloroformate in dry tetrahydrofuran at -15° C. The resulting protected tripeptide was deblocked by treatment with hydrogen in the presence of 10% palladium on carbon in glacial acetic acid. Filtration and lyophilization gave the title compound as its triacetate salt. was added to a solution Filtration and lyophilization

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

実験手順: The resulting fully protected dipeptide ester is treated with 1/1 trifiuoroacetic acid/dichloromethane at room temperature, neutralized with saturated aqueous sodium bicarbonate solution, and extracted into ethyl acetate. Evaporation gives the partially deblocked dipeptide, which is redissolved in dry THF and added to a stirring solution of benzyloxycarbonylglycine, N-methylmorpholine, and isobutyl chloroformate in dry THF at -15° C. The formed, fully protected tripepride ester is totally deblocked by treatment with hydrogen gas in glacial acetic acid at room temperature in the presence of Pd-C catalyst. Filtration, evaporation and purification on a microcrystalline cellulose column followed by lyophilization give the desired tripepride ester as its triacetate salt. Filtration, evaporation and purification on a microcrystalline cellulose column