Backbone amide linker (BAL) strategy for Nα-9-fluorenylmethoxycarbonyl (Fmoc) solid-phase synthesis of peptide aldehydes

Joseph C. Kappel, George Barany

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

A rapid and efficient strategy has been developed for the general synthesis of complex peptide aldehydes. Nα-Benzyloxycarbonylamino acids were converted to protected aldehyde building blocks for solid-phase synthesis in four steps and moderate overall yields. The aldehydes were protected as 1,3-dioxolanes except for one case where a dimethyl acetal was used. These protected amino aldehyde monomers were then incorporated onto 5-[(2 or 4)-formyl-3,5-dimethoxyphenoxy]butyryl-resin (BAL-PEG-PS) by reductive amination, following which the penultimate residue was introduced by HATU-mediated acylation. The resultant resin-bound dipeptide unit, anchored by a backbone amide linkage (BAL), was extended further by routine Fmoc chemistry procedures. Several model peptide aldehydes were prepared in good yields and purities. Some epimerization of the C-terminal residue occurred (10% to 25%), due to the intrinsic stereolability conferred by the aldehyde functional group, rather than any drawbacks to the synthesis procedure. Coyright

Original languageEnglish (US)
Pages (from-to)525-535
Number of pages11
JournalJournal of Peptide Science
Volume11
Issue number9
DOIs
StatePublished - Sep 2005

Keywords

  • 1,3-dioxolanes
  • Backbone amide linker (BAL)
  • Dimethyl acetals
  • Peptide aldehydes
  • Protease inhibitors
  • Solid-phase synthesis

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