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

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 p-p-interactions in the transition state.