title: DBU as an N alpha-deprotecting reagent for the fluorenylmethoxycarbonyl group in continuous flow solid-phase peptide synthesis.
abstract: The versatility and efficiency of the N alpha-fluorenylmethoxycarbonyl method of solid-phase peptide synthesis have been further enhanced by recent and continuing refinements in side-chain protecting group, linker and amino acid-coupling technology. In contrast, comparatively little work has been carried out on studying and further improving the N alpha-deprotection step. This report demonstrates that, in low concentrations, the non-nucleophilic amidine 1,8-diazabicyclo[5.4.0]undec-7-ene is a preferred alternative to the more commonly employed piperidine for the rapid and efficient cleavage of the N alpha-fluorenylmethoxycarbonyl group in the continuous flow method of solid-phase peptide synthesis. In the cases studied, use of this base did not cause cyclization of Asp(OBut)-Gly or Asn-Gly sequence to succinimide derivatives. At the recommended concentration of 2% 1,8-diazabicyclo[5.4.0]undec-7-ene in dimethylformamide, racemization of resin-bound C-terminal S-trityl cysteine was substantially reduced compared with standard piperidine-mediated deprotection conditions. Additionally, use of the base appears to reduce the extent of broadening of ultraviolet fluorenylmethoxycarbonyl-deprotection peaks occasionally observed when piperidine is employed, indicating that its reaction kinetics and mode of action are different.
authors.affiliation: Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: J D
authors.initials: JD
authors.lastname: Wade
authors.forename: J
authors.initials: J
authors.lastname: Bedford
authors.forename: R C
authors.initials: RC
authors.lastname: Sheppard
authors.forename: G W
authors.initials: GW
authors.lastname: Tregear
mesh_terms: D000595:Amino Acid Sequence; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003545:Cysteine / Q000737:chemistry; D004126:Dimethylformamide; D005449:Fluorenes; D007202:Indicators and Reagents; D008969:Molecular Sequence Data; D009757:Nylons; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D010880:Piperidines
chemical_list: D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005449:Fluorenes; D007202:Indicators and Reagents; D009757:Nylons; D010455:Peptides; D010880:Piperidines; C069171:fluorenylmethoxycarbonyl-polyamide; C032727:piperidine; D004126:Dimethylformamide; C031033:1,8-diazabicyclo(5.4.0)undec-7-ene; D003545:Cysteine