Synthetic and mechanistic insight into nosylation of glycine residuesElectronic supplementary information (ESI) available. See DOI: 10.1039/c3ob00014a
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 observatio...
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Main Authors | , , |
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Format | Journal Article |
Language | English |
Published |
13.03.2013
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Online Access | Get full text |
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Summary: | 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.
The glycine residue is the only primary amine moiety undergoing bis-nosylation upon reaction with an excess of nosyl chloride. |
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Bibliography: | 10.1039/c3ob00014a Electronic supplementary information (ESI) available. See DOI |
ISSN: | 1477-0520 1477-0539 |
DOI: | 10.1039/c3ob00014a |