ISBN 9783843922678

978-3-8439-2267-8, Reihe Organische Chemie

Carina Susanne Hagemann
Ein katalytisch-enantioselektiver Zugang zu 3-substituierten Prolinderivaten und homologen Verbindungen als Bausteine zur Synthese von konformationell fixierten Peptidmimetika

251 Seiten, Dissertation Universität Köln (2015), Softcover, A5

Zusammenfassung / Abstract

The present work makes a contribution to the stereoselective synthesis of trans-configurated 3-substituted proline derivatives. Starting from diprotected dehydroproline esters, which are available in a two to three step synthesis from L-proline, a wide range of various proline derivatives bearing an alkyl-, alkenyl-, or aryl-substituent at position-3 were synthesized in a racemic manner. For the development of an enantioselective access to 3-vinylprolines different methods were tried out based on a copper-catalyzed 1,4-addition of Grignard reagents in the presence of chiral ligands and on a phasetransfer-catalyzed conjugate addition of glycine esters to aldehydes. In this context chiral phosphine phosphite ligands with different functionalized backbones developed by Schmalz group were prepared. The provision of several grams of optically active 3-vinylproline was successfully realised by racemate resolution. Furthermore the stereoselective synthesis of two vinyl-substituted amino acids, serving as important building blocks for the provision of peptidomimetics, were optimized and conducted in gram scale. In conclusion, a proline-proline-dipeptidomimetic in a PPII-helix-conformation is deliverd based on an established concept. This secondary structure mimetic were then incorporated into proline rich ligands at the ’’Forschungsinstitut für molekulare Pharmakologie’’ (FMP) in Berlin and analyzed on their binding affinity to proline rich domains.