Synthesis of aza-spirocyclic dienones and their application toward natural product synthesis and synthesis and evaluation of anticancer tetracyclic indole containing compounds

A novel route to access the aza-spirocyclic cross-conjugated dienone motif was developed utilizing an intramolecular phenolic C-alkylation and Suzuki coupling to form the key quaternary carbon center. A chemoselective addition of crotyl silane to the azaspirocyclic dienone motif was developed in an effort to synthesize the spirobicyclononane core of (±)-aspernomine and (±) sespenine. The structure-activity-relationship of anticancer tetracyclic indole containing compounds was developed via the synthesis and biological evaluation of 48 novel derivatives. Additionally, tool compounds containing a biotin and photoaffinity crosslinker were synthesized for use in future target identification studies.