title: Use of Fmoc-N-(2-hydroxy-4-methoxybenzyl)amino acids in peptide synthesis.
abstract: The use of N,O-bisFmoc-N-(2-hydroxy-4-methoxybenzyl)amino acid derivatives in the synthesis of peptides with difficult sequences has already been described. With these amino acid derivatives the reversible protecting group 2-hydroxy-4-methoxybenzyl (Hmb) for the backbone amide bonds of peptide chains is introduced, and thus the aggregation due to hydrogen-bond interchain association is inhibited. This paper describes the synthesis and use of Fmoc-N-(2-hydroxy-4-methoxybenzyl)amino acid derivatives as an alternative means of introducing Hmb backbone protection. These new monoFmoc derivatives were obtained in higher yield than the bisFmoc derivatives. Coupling yields to the amino peptide resin were the same as those obtained with bisFmoc derivatives, under the TBTU HOBt/DIEA conditions. We also compared different syntheses of a difficult peptide with the Fmoc approach [triple coupling, capping, use of chaotropic agents, backbone protection using monoFmoc (Hmb)Ala] and with optimized Boc chemistry. Both the backbone protection and optimized Boc chemistry approaches gave the desired product in excellent yield and purity.
authors.affiliation: CMU, Geneva, Switzerland.
authors.forename: W
authors.initials: W
authors.lastname: Zeng
authors.forename: P O
authors.initials: PO
authors.lastname: Regamey
authors.forename: K
authors.initials: K
authors.lastname: Rose
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: E
authors.initials: E
authors.lastname: Bayer
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D005449:Fluorenes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis*; D009975:Orthomyxoviridae / Q000737:chemistry; D014764:Viral Proteins / Q000737:chemistry
chemical_list: D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D009842:Oligopeptides; D014764:Viral Proteins