The class of prenylated indole alkaloids known as the ambiguines represents an intriguing class of compounds due to their biological activity including antibiotic and anti-fungal properties. Perhaps a more fascinating feature of these natural products is their biosynthesis, which is suggested to involve the class of non-heme C-H functionalizing enzymes known as the Rieske-oxygenases. It has been proposed that these enzymes are responsible for the final oxidative diversification among the ambiguines including ring closure, epoxidation, and dihydroxylation. While a synthesis of tetracyclic (+)-ambiguine H was recently reported by Baran and coworkers, a synthesis of any of the pentacyclic ambiguines has not yet been accomplished. We envision that a divergent total synthesis of these densely functionalized indole alkaloids will help elucidate mechanisms for the final Rieske mediated oxidations and encourage further biological studies. In light of this goal we present progress toward the synthesis of the pentacyclic class of ambiguines utilizing a strategy which provides direct access to the requisite C2-substituted indole precursors.

Synthetic efforts toward the ambiguine class of natural products

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.