Synthesis and structural analysis of cyclic oligomers consisting of furanoid and pyranoid ε-sugar amino acids

Renate M. Van Well, Luciana Marinelli, Kees Erkelens, Gijsbert A. Van der Marel, Antonio Lavecchia, Herman S. Overkleeft, Jacques H. Va Boom, Horst Kessler, Mark Overhand

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Cyclic oligomers composed of amide-linked furanoid (i.e., 1, 3) and pyranoid (i.e., 2, 4) ε-sugar amino acids (SAAs) were prepared by a cyclization/cleavage approach with use of the oxime resin. These cyclic homooligomers were constructed by use of the known N-Boc protected furanoid ε-SAA 11 and the novel pyranoid hydroxymethylene homologue 22. Conformational analysis of cyclic trimer 1 by an unrestrained simulated annealing technique showed that the furanoid rings of the residues I flip between a twist (north, P = 0°) and an envelope (south, P = 167°) conformation. Furthermore, the side chains connecting the carbonyl functionality (i.e. C2) proved to be rigid, while the other side chains (C7) are conformationally flexible. Similar conformational behaviour is observed for the side chains of the pyranoid ε-SAA II residues in trimer 2, but the pyranoid ring chair conformation remains stable during the calculation. These conformational details may have important implications in the future design of SAA-based artificial receptors or peptidomimetics.

Original languageEnglish
Pages (from-to)2303-2313
Number of pages11
JournalEuropean Journal of Organic Chemistry
Issue number12
StatePublished - Jun 2003

Keywords

  • Amino acids
  • Conformational analysis
  • Cyclization
  • Molecular dynamics

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