Development of Novel Routes and Methods for the Semisynthesis of the Marine Steroid Demethylgorgosterol and Unnatural Analogs

Beiträge zur organischen Synthese, Bd. 97

Nicolai Rosenbaum

ISBN 978-3-8325-5516-0
299 pages, year of publication: 2022
price: 50.50 €

Gorgosterol and its derivative demethylgorgosterol are two long known marine steroids with unusual properties and a unique structure, containing a cyclopropane moiety in the side chain. Gorgosterol and its derivatives show diverse structural motives and biological activities. Moreover, corals and coral reefs have a tremendous ecological and economic impact but are endangered by climate change. A better understanding of corals can therefore aid their protection and conservation.

A concise and high yielding formal semisynthesis for the marine steroid demethylgorgosterol was developed. Centerpiece was a stereoselective intermolecular cyclopropanation. A variety of demethylgorgosterol analogs were synthesized for biological applications. These include hydrocarbon analogs, diversely functionalized analogs, and fluorophore-steroid conjugates to track and visualize steroids in vivo. Finally, a new method for the synthesis of 3-cyclopropylacrylates was developed. Here, a vinylogous diazoester was utilized to cyclopropanate alkenes. The observed cis-selectivity was explained with π-π-interactions in the transition state.