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Synthesis and application of N α ‐Fmoc‐ N π ‐4‐methoxybenzyloxymethylhistidine in solid phase peptide synthesis
Author(s) -
Hibino Hajime,
Miki Yasuyoshi,
Nishiuchi Yuji
Publication year - 2012
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2464
Subject(s) - racemization , peptide synthesis , chemistry , trifluoroacetic acid , residue (chemistry) , solid phase synthesis , protecting group , imidazole , peptide , combinatorial chemistry , crystallization , dichloromethane , organic chemistry , alkyl , biochemistry , solvent
The 4‐methoxybenzyloxymethyl (MBom) group was introduced at the N π ‐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 N π ‐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.