Synthesis and Structural Analysis of Cyclic Oligomers Consisting of Furanoid and Pyranoid ϵ-Sugar Amino Acids

• Published in: European journal of organic chemistry Vol. 2003; no. 12; pp. 2303 - 2313
• Main Authors: Well, Renate M. van, Marinelli, Luciana, Erkelens, Kees, Marel, Gijsbert A. van der, Lavecchia, Antonio, Overkleeft, Herman S., Boom, Jacques H. van, Kessler, Horst, Overhand, Mark
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.06.2003; WILEY‐VCH Verlag; Wiley
• Subjects: Amino acids; Chemistry; Chemistry, Organic; Conformational analysis; Cyclization; Molecular dynamics; Physical Sciences; Science & Technology; SOLID-PHASE-SYNTHESIS; MIMETICS; BUILDING-BLOCKS; PSEUDOROTATION; amino acids; CYCLODEXTRINS; CARBOPEPTOIDS; molecular dynamics; cyclization; PEPTIDOMIMETICS; 5-MEMBERED RINGS; SECONDARY STRUCTURE; conformational analysis; CONFORMATIONAL-ANALYSIS
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200300031

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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)