title: Synthesis and application of Nα-Fmoc-Nπ-4-methoxybenzyloxymethylhistidine in solid phase peptide synthesis.
abstract: 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.
authors.affiliation: SAITO Research Center, Peptide Institute, Inc., Ibaraki, Osaka, 567-0085, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Hibino
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Miki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishiuchi
mesh_terms: D000840:Anisoles / Q000138:chemical synthesis* / Q000302:isolation & purification; D003460:Crystallization; D006639:Histidine / Q000138:chemical synthesis* / Q000302:isolation & purification; D008872:Microwaves; D009479:Neuropeptides / Q000138:chemical synthesis*; D060327:Solid-Phase Synthesis Techniques
chemical_list: D000840:Anisoles; D009479:Neuropeptides; D006639:Histidine
keywords: 4-methoxybenzyloxymethyl (MBom) group; histidine; microwave (MW)-assisted solid phase peptide synthesis (SPPS); protecting group; racemization