Peptide synthesis in water IV. Preparation of N-ethanesulfonylethoxycarbonyl (Esc) amino acids and their application to solid phase peptide synthesis.
A new N-protecting group, ethanesulfonylethoxycarbonyl (Esc), was designed to perform peptide synthesis in both aqueous and organic solvents. Esc-amino acids were prepared by the reaction of Esc-Cl and amino acids. Although Esc-Cl was a highly reactive reagent, it was not stable and decomposed during the purification procedure. A more stable reagent, ethanesulfonylethyl-4-nitrophenyl carbonate (Esc-ONp), was designed for preparation of Esc-amino acids. Esc-ONp was a stable reagent and could be purified by silica gel column chromatography or recrystallization. Esc-amino acids were prepared by the reaction of Esc-ONp and amino acids in good yield. To evaluate Esc-amino acids, Leu-enkephalin amide was synthesized using Esc-amino acids by the solid phase method in water. Removal of the Esc group was performed with 0.025 mol/l NaOH in 50% aqueous ethanol. Leu-enkephalin amide was successfully synthesized on a poly(ethylene glycol)-grafted polystyrene resin. Esc-amino acids have moderate solubility in organic solvents (such as dimethylformamide and acetonitrile). Leu-enkephalin amide was synthesized using Esc-amino acids by the solid phase method in dimethylformamide. Removal of the Esc group was performed with 0.05 mol/l tetrabutylammonium fluoride in dimethylformamide. Synthesis of Leu-enkephalin amide using Esc-amino acids in dimethylformamide was also successful. The yields of synthesis of Leu-enkephalin amide in water and dimethylformamide were 71% and 67%, respectively.
Hojo
Keiko
K
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Maeda
Mitsuko
M
Smith
Timothy J
TJ
Kita
Eriko
E
Yamaguchi
Fumie
F
Yamamoto
Sachiko
S
Kawasaki
Koichi
K
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004743:Enkephalin, Leucine / Q000138:chemical synthesis; D007202:Indicators and Reagents; D010455:Peptides / Q000138:chemical synthesis*; D012995:Solubility; D014867:Water
D000596:Amino Acids; D007202:Indicators and Reagents; D010455:Peptides; D014867:Water; D004743:Enkephalin, Leucine