Synthetic and mechanistic insight into nosylation of glycine residues
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Synthetic and mechanistic insight into nosylation of glycine residues. / Stuhr-Hansen, Nicolai; Sølling, Theis Ivan; Strømgaard, Kristian.
In: Organic & Biomolecular Chemistry, Vol. 11, No. 14, 14.04.2013, p. 2288-2293.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Synthetic and mechanistic insight into nosylation of glycine residues
AU - Stuhr-Hansen, Nicolai
AU - Sølling, Theis Ivan
AU - Strømgaard, Kristian
PY - 2013/4/14
Y1 - 2013/4/14
N2 - The Fukuyama-Mitsunobu alkylation procedure is widely used to introduce alkyl substituents to amino groups in general and N-alkylation of peptides in particular. Here we have investigated the procedure in detail for N-alkylation of peptides with N-terminal glycine residues, based on the observation that standard conditions lead to substantial bis-nosylation of the glycine amino group. A systematic evaluation of this observation was carried out and it was demonstrated that for peptides with alanine, β-alanine or γ-aminobutyric acid (GABA) as N-terminal residues mono-nosylation was observed under the same conditions. Moreover, bis-nosylation was independent of the type of resin, neighboring amino acid and nature of the peptide. Calculations suggest that the reason for the bis-nosylation is the fact that the deprotonated mono-nosyl species is particularly stable in the case of the terminal Gly residue because the N(-) residue can become closer to the SO(2) unit. Finally, the mono-nosylated N-terminal glycine could be obtained by careful optimization of the procedure, adding only one equivalent of 2-nitrobenzenesulfonyl chloride.
AB - The Fukuyama-Mitsunobu alkylation procedure is widely used to introduce alkyl substituents to amino groups in general and N-alkylation of peptides in particular. Here we have investigated the procedure in detail for N-alkylation of peptides with N-terminal glycine residues, based on the observation that standard conditions lead to substantial bis-nosylation of the glycine amino group. A systematic evaluation of this observation was carried out and it was demonstrated that for peptides with alanine, β-alanine or γ-aminobutyric acid (GABA) as N-terminal residues mono-nosylation was observed under the same conditions. Moreover, bis-nosylation was independent of the type of resin, neighboring amino acid and nature of the peptide. Calculations suggest that the reason for the bis-nosylation is the fact that the deprotonated mono-nosyl species is particularly stable in the case of the terminal Gly residue because the N(-) residue can become closer to the SO(2) unit. Finally, the mono-nosylated N-terminal glycine could be obtained by careful optimization of the procedure, adding only one equivalent of 2-nitrobenzenesulfonyl chloride.
U2 - 10.1039/c3ob00014a
DO - 10.1039/c3ob00014a
M3 - Journal article
C2 - 23420089
VL - 11
SP - 2288
EP - 2293
JO - Organic & Biomolecular Chemistry
JF - Organic & Biomolecular Chemistry
SN - 1470-4358
IS - 14
ER -
ID: 45795472