Universität zu Köln

Reuter, Cedric, Huy, Peter ORCID: 0000-0002-5099-5988, Neudoerfl, Joerg-Martin, Kuehne, Ronald and Schmalz, Hans-Guenther ORCID: 0000-0003-0489-1827 (2011). Exercises in Pyrrolidine Chemistry: Gram Scale Synthesis of a Pro-Pro Dipeptide Mimetic with a Polyproline Type II Helix Conformation. Chem.-Eur. J., 17 (43). S. 12037 - 12045. MALDEN: WILEY-BLACKWELL. ISSN 0947-6539

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Abstract

A practical and scalable synthesis of a Fmoc-protected tricyclic dipeptide mimetic (6), that is, a 1,4-diaza-tricyclo-[8.3.0(3,7)]-tridec-8-ene derivative resembling a rigidified di-L-proline in a polyproline type II (PPII) helix conformation, was developed. The strategy is based on a Ru-catalyzed ring-closing metathesis of a dipeptide (4) prepared by PyBOP coupling of cis-5-vinylproline tert-butylester (2) and trans-N-Boc-3-vinylproline (rac-3) followed by chromatographic diastereomer separation. Building block 2 was prepared from l-proline in six steps via electrochemical C5-methoxylation, cyanation and conversion of the nitrile into a vinyl substituent. Building block rac-3 was prepared in five steps exploiting a Cu-catalyzed 1,4-addition of vinyl-MgBr to a 2,3-dehydroproline derivative in the key step. In the course of the investigation subtle dependencies of protecting groups on the reactivity of the 2,3- and 2,5-disubstituted pyrrolidine derivatives were observed. The configuration and conformational preference of several intermediates were determined by Xray crystallography. The developed synthesis allows the preparation of substantial amounts of 6, which will be used in the search for new small molecules for the modulation of protein-protein interactions involving prolin-rich motifs (PRDs).

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Reuter, Cedric UNSPECIFIED UNSPECIFIED UNSPECIFIED Huy, Peter UNSPECIFIED orcid.org/0000-0002-5099-5988 UNSPECIFIED Neudoerfl, Joerg-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuehne, Ronald UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmalz, Hans-Guenther UNSPECIFIED orcid.org/0000-0003-0489-1827 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-488354
DOI:	10.1002/chem.201101704
Journal or Publication Title:	Chem.-Eur. J.
Volume:	17
Number:	43
Page Range:	S. 12037 - 12045
Date:	2011
Publisher:	WILEY-BLACKWELL
Place of Publication:	MALDEN
ISSN:	0947-6539
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN-PROTEIN INTERACTIONS; AMINO-ACIDS; OLEFIN METATHESIS; ORGANIC-SYNTHESIS; L-PROLINE; MACROMOLECULAR INTERACTIONS; ELECTROCHEMICAL OXIDATION; ELECTROORGANIC CHEMISTRY; TRIMETHYLSILYL IODIDE; PEPTIDE MIMETICS Multiple languages Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48835