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Design, Synthesis, NMR-Solution and X-Ray Crystal Structure ofN-Acyl-γ-dipeptide Amides That Form aβII′-Type Turn

2001; Wiley; Volume: 84; Issue: 8 Linguagem: Inglês

10.1002/1522-2675(20010815)84

1522-2675

Meinrad Brenner, Dieter Seebàch,

Cancer therapeutics and mechanisms

Helvetica Chimica ActaVolume 84, Issue 8 p. 2155-2166 Research Article Design, Synthesis, NMR-Solution and X-Ray Crystal Structure of N-Acyl-γ-dipeptide Amides That Form a βII′-Type Turn Meinrad Brenner, Meinrad Brenner Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH-Zentrum, Universitätstrasse 16, CH-8092 ZürichSearch for more papers by this authorDieter Seebach, Dieter Seebach Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH-Zentrum, Universitätstrasse 16, CH-8092 ZürichSearch for more papers by this author Meinrad Brenner, Meinrad Brenner Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH-Zentrum, Universitätstrasse 16, CH-8092 ZürichSearch for more papers by this authorDieter Seebach, Dieter Seebach Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH-Zentrum, Universitätstrasse 16, CH-8092 ZürichSearch for more papers by this author First published: 26 September 2001 https://doi.org/10.1002/1522-2675(20010815)84:8 3.0.CO;2-8Citations: 40 Part of the Ph. D. thesis of M. B., ETH-Zürich, 2001. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Conformational analysis of γ-amino acids with substituents in the 2-position reveals that an N-acyl-γ-dipeptide amide built of two enantiomeric residues of unlike configuration will form a 14-membered H-bonded ring, i.e., a γ-peptidic turn (Figs. 1 – 3). The diastereoselective preparation of the required building blocks was achieved by alkylation of the doubly lithiated N-Boc-protected 4-aminoalkanoates, which, in turn, are readily available from the corresponding (R)- or (S)-α-amino acids (Scheme 1). Coupling two such γ-amino acid derivatives gave N-acetyl and N-[(tert-butoxy)carbonyl] (Boc) dipeptide methyl amides (1 and 10, resp.; Fig. 2, Scheme 2); both formed crystals suitable for X-ray analysis, which confirmed the turn structures in the solid state (Fig. 4 and Table 4). NMR Analysis of the acetyl derivative 1 in CD3OH, with full chemical-shift and coupling assignments, and, including a 300-ms ROESY measurement, revealed that the predicted turn structure is also present in solution (Fig. 5 and Tables 1 – 3). The results described here are yet another piece of evidence for the fact that more stable secondary structures are formed with a decreasing number of residues, and with increasing degree of predictability, as we go from α- to β- to γ-peptides. Implications of the superimposable geometries of the actual turn segments (with amide bonds flanked by two quasi-equatorial substituents) in α-, β-, and γ-peptidic turns are discussed. Citing Literature Volume84, Issue8August 15, 2001Pages 2155-2166 RelatedInformation