Universität zu Köln

Soicke, Arne, Reuter, Cedric, Winter, Matthias, Neudoerfl, Joerg-Martin, Schloerer, Nils ORCID: 0000-0002-0990-9582, Kuehne, Ronald and Schmalz, Hans-Guenther ORCID: 0000-0003-0489-1827 (2014). Stereoselective Synthesis of Tricyclic Diproline Analogues that Mimic a PPII Helix: Structural Consequences of Ring-Size Variation. Eur. J. Org. Chem., 2014 (29). S. 6467 - 6481. WEINHEIM: WILEY-V C H VERLAG GMBH. ISSN 1099-0690

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Abstract

Polycyclic proline-derived scaffolds (ProMs) have recently demonstrated their value as conformationally defined dipeptide analogs for the modular construction of secondary structure mimetics, specifically interfering with PPII helix-mediated protein-protein interactions. We disclose the stereoselective synthesis of two new tricyclic amino acid scaffolds (ProM-4 and ProM-8) that differ from the first generation scaffold ProM-1 by the size of ring A. Conformational preferences and subtle structural differences of the three homologous scaffolds were analyzed by X-ray crystallography, computational calculations, and NMR spectroscopy. N-tert-butoxycarbonyl(Boc)-3-(1-propenyl) azetidine-2-carboxylic acid was prepared from L-aspartic acid through beta-lactam intermediates. The corresponding piperidine-based building block rac-N-Boc-3-vinylpipecolic acid was synthesized by Cu-catalyzed 1,4-addition of vinyl-MgBr to methyl N-Boc-2,3-dehydropipecolate. Target molecules were prepared through peptide coupling of the respective ring A building blocks with cis-5-vinylproline tert-butyl ester and subsequent ring-closing metathesis. Selective deprotection of a tert-butyl carbamate (N-Boc protecting group) in the presence of a tert-butyl ester was achieved with trifluoroacetic acid at 0 degrees C.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Soicke, Arne UNSPECIFIED UNSPECIFIED UNSPECIFIED Reuter, Cedric UNSPECIFIED UNSPECIFIED UNSPECIFIED Winter, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Neudoerfl, Joerg-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schloerer, Nils UNSPECIFIED orcid.org/0000-0002-0990-9582 UNSPECIFIED Kuehne, Ronald UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmalz, Hans-Guenther UNSPECIFIED orcid.org/0000-0003-0489-1827 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-427959
DOI:	10.1002/ejoc.201402737
Journal or Publication Title:	Eur. J. Org. Chem.
Volume:	2014
Number:	29
Page Range:	S. 6467 - 6481
Date:	2014
Publisher:	WILEY-V C H VERLAG GMBH
Place of Publication:	WEINHEIM
ISSN:	1099-0690
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Organic Chemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN-PROTEIN INTERACTIONS; REDUCTION; PEPTIDOMIMETICS; BISAZETIDINES; THIENAMYCIN; INHIBITION; MODULATION; AZETIDINES; CHEMISTRY; EFFICIENT Multiple languages Chemistry, Organic Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/42795