ISBN 978-3-8439-5045-9

978-3-8439-5045-9, Reihe Organische Chemie

Julian Lasse Baars
Enantioselective Total Synthesis and Structural Revision of Dysiherbol A

320 Seiten, Dissertation Universität Köln (2022), Hardcover, A5

Zusammenfassung / Abstract

Marine sponges currently attract the attention of researchers all over the world as they are a valuable source of structurally diverse natural products covering a broad range of promising biological properties. The recently isolated meroterpene dysiherbol A from Dysidea sp. has proven to be a strong NF κB inhibitor, capable of affecting inflammatory, immunological and carcinogenic processes. Dysiherbol A furthermore possesses a novel 6/6/5/6-carbocyclic skeleton exhibiting five continuous stereocenters with three quaternary carbon atoms.

This work describes the total synthesis of the unnatural (−)-enantiomer of dysiherbol A via two different synthetic strategies (11-14 linear steps). After an enantioselective Cu-catalyzed 1,4 addition/enolate trapping as the chirogenic opening step, the tetracyclic carbon skeleton was assembled through either a Friedel-Crafts-type intramolecular 1,4-addition or a AuCl3-catalyzed double cyclization approach. The final pentacyclic structure of dysiherbol A was then established via a proton-induced cyclopropane opening under formation of the ether bridge, ultimately leading to a revision of the originally proposed structure. Specifically, both the constitution (as the corresponding cyclic anhydride) and the absolute configuration had to be revised, which was secured by X-ray crystallography and CD spectroscopy. In this way, this work highlights the importance of total synthesis for both structure elucidation and production of natural products for further pharmacological investigation.