反应详情

To the chloroform solution (30 ml) of H-Glu(OtBu)-Tyr(tBu)-Leu-OBzl was added HOBt (68 mg, 0.50 mmol), Fmoc-Glu(OtBu)-OH (468 mg, 1.10 mmol) and EDC.HCl (232 mg, 1.21 mmol) were added under ice-cooling, and the mixture was stirred at room temperature overnight. After completion of the reaction, the solvent was evaporated under reduced pressure until the mixture became 15 mL, to the concentrated solution were added under ice-cooling thiomalic acid (450 mg, 3.00 mmol) and DBU (1.34 mL, 9.00 mmol), and the mixture was stirred at room temperature for 3 hr. After completion of the reaction, to this solution was added dropwise under ice-cooling a mixture of MsOH (0.17 mL, 2.70 mmol) and chloroform (1.7 mL), chloroform (15 mL) and 20% brine (30 ml) was added to give an organic layer and an aqueous layer. Then, the aforementioned pH=9.0 washing was performed three times. The obtained organic layer was washed three times with 10% aqueous sodium carbonate solution (30 ml) and twice with 20% brine (30 ml) with stirring at room temperature, and the organic layer and the aqueous layer were partitioned. The obtained organic layer was dried over sodium sulfate and filtered. The filtrate was recovered, and the solvent in the recovered filtrate was evaporated under reduced pressure. To the obtained residue was added hexane (10 ml), and the precipitate was recovered by filtration. The recovered precipitate was dried to give H-Glu(OtBu)-Glu(OtBu)-Tyr(tBu)-Leu-OBzl (787 mg, 0.97 mmol). The yield of the finally obtained C-protected peptide was calculated from H-Leu-OBzl.TsOH salt (1.00 mmol), which is the starting material of Example 5(i), to find 97%.

1. additionwere added under ice-
2. temperaturecooling
3. customAfter completion of the reaction
4. customthe solvent was evaporated under reduced pressure until the mixture
5. additionto the concentrated solution were added under ice-
6. stirringthe mixture was stirred at room temperature for 3 hr
7. customAfter completion of the reaction
8. additionto this solution was added dropwise under ice-
9. temperaturecooling
10. additionwas added
11. customto give an organic layer
12. washThen, the aforementioned pH=9.0 washing
13. washThe obtained organic layer was washed three times with 10% aqueous sodium carbonate solution (30 ml)
14. stirringtwice with 20% brine (30 ml) with stirring at room temperature
15. customthe organic layer and the aqueous layer were partitioned
16. dry with materialThe obtained organic layer was dried over sodium sulfate
17. filtrationfiltered
18. customThe filtrate was recovered
19. customthe solvent in the recovered filtrate was evaporated under reduced pressure
20. additionTo the obtained residue was added hexane (10 ml)
21. filtrationthe precipitate was recovered by filtration
22. customThe recovered precipitate was dried