Synthesis and application of Nα-Fmoc-Nπ-4-methoxybenzyloxymethylhistidine in solid phase peptide synthesis
Version of Record online: 30 OCT 2012
Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Volume 18, Issue 12, pages 763–769, December 2012
How to Cite
Hibino, H., Miki, Y. and Nishiuchi, Y. (2012), Synthesis and application of Nα-Fmoc-Nπ-4-methoxybenzyloxymethylhistidine in solid phase peptide synthesis. J. Peptide Sci., 18: 763–769. doi: 10.1002/psc.2464
- Issue online: 13 NOV 2012
- Version of Record online: 30 OCT 2012
- Manuscript Accepted: 9 OCT 2012
- Manuscript Revised: 8 OCT 2012
- Manuscript Received: 8 SEP 2012
- 4-methoxybenzyloxymethyl (MBom) group;
- microwave (MW)-assisted solid phase peptide synthesis (SPPS);
- protecting group;
The 4-methoxybenzyloxymethyl (MBom) group was introduced at the Nπ-position of the histidine (His) residue by using a regioselective procedure, and its utility was examined under standard conditions used for the conventional and the microwave (MW)-assisted solid phase peptide synthesis (SPPS) with 9-fluorenylmethyoxycarbonyl (Fmoc) chemistry. The Nπ-MBom group fulfilling the requirements for the Fmoc strategy was found to prevent side-chain-induced racemization during incorporation of the His residue even in the case of MW-assisted SPPS performed at a high temperature. In particular, the MBom group proved to be a suitable protecting group for the convergent synthesis because it remains attached to the imidazole ring during detachment of the protected His-containing peptide segments from acid-sensitive linkers by treatment with a weak acid such as 1% trifluoroacetic acid in dichloromethane. We also demonstrated the facile synthesis of Fmoc-His(π-MBom)-OH with the aid of purification procedure by crystallization to effectively remove the undesired τ-isomer without resorting to silica gel column chromatography. This means that the present synthetic procedure can be used for large-scale production without any obstacles. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.