反应详情

To a solution of 115 mg of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidine hydrazide in 2 ml of N,N-dimethylformamide were added successively dropwise 0.16 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.04 ml of isoamyl nitrite under ice-cooling, and mixture was stirred. After disappearance of hydrazide compound, the reaction mixture was cooled to -30° C., and neutralized by adding 0.11 ml of triethylamine to prepare a solution of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidine azide. The azide solution was added dropwise to a solution of 63 mg of (2RS, 3S)-3-amino-2-hydroxy-5-methylhexyl isoamyl ether and 0.035 ml of triethylamine in 2 ml of N,N-dimethylformamide solution 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 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/water32 8/3/1 by volume) to obtain 51 mg of (2RS, 3S)-3-{N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)-propionyl]-L-histidyl}amino-2-hydroxy-5-methylhexyl isoamyl ether as a white powder.

1. temperaturecooling
2. stirringthe mixture was stirred for 16 hours under ice-
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 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/water32 8/3/1 by volume)