反应详情

To a solution of 64 mg of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidine hydrazide in 2 ml of N,N-dimethylformamide were added successively dropwise 0.09 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.022 ml of isoamyl nitrite at -20° C., and the mixture was stirred under ice-cooling. After disappearance hydrazide compound, the reaction mixture was cooled to -30° C., and neutralized by adding 0.063 ml of triethylamine to prepare a solution of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]--histidine azide. The azide solution was added dropwise to a solution of 40 mg of (2RS, 3S)-N-isoamyl-3-amino-2-hydroxy-5-methylhexylamine dihydrochloride in 2 ml of N,N-dimethylformamide under ice-cooling, and the mixture was stirred for 16 hours under ice-cooling. A 5% aqueous sodium bicarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by preparative silica gel thin layer chromatography (developing solvent: lower layer of chloroform/methanol/water=8/3/1 by volume) to obtain 8 mg of (2RS, 3S)-N-isoamyl-3-{N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidyl}amino-2-hydroxy-5-methylhexylamine as a white powder.

1. temperaturecooling
2. temperaturecooling
3. temperaturecooling
4. extractionthe mixture was extracted with ethyl acetate
5. washThe ethyl acetate layer was washed with a saturated sodium chloride aqueous solution
6. dry with materialdried over anhydrous magnesium sulfate
7. customevaporated under reduced pressure
8. customThe residue was purified by preparative silica gel thin layer chromatography (developing solvent: lower layer of chloroform/methanol/water=8/3/1 by volume)