Schutzgruppenfreie enantioselektive Totalsynthese von Ecklonialacton A und B sowie biologische Tests aktiver Naturstoffe

Abstract

The focus of this doctoral thesis was on the synthesis of members and analogues of a broader family of marine oxylipins. A modular, first and enantioselective protecting-group free total synthesis of Ecklonialactones A and B is described. The chiral information is introduced at the very beginning of the synthesis either by means of (-)-menthol as a chiral auxiliary or by the chiral ligands in a Rhodiumcatalyzed 1,4-addition. All further reactions proceed under substrate-control with very high diastereoselectivities. The 14-membered macrolactone is obtained by a ringclosing alkyne metathesis (RCAM) using newly available, highly active Molybdenumalkylidyne complexes under very mild reaction conditions. Additionally, the results of NMR-investigations on Ecklonialactone A are presented. The epoxide of this natural product was opened regioselectively to give Eiseniachloride A. More surprisingly, a rearrangement has also lead to a chlorinated, cyclopropane-containing derivative of an unnamed natural product. Finally, a non-natural derivative of Hybridalactone ("Desethyl-hybridalactone") has been synthesized, and further work towards the synthesis of natural Hybridalactone is also presented. In the second part of this thesis, the results of cytotoxicity assays using cancer cell lines and synthetic natural products, especially the Ipomoeassins, are described. Simple structure-activity-relationships were found among this group of natural products.