Synthetic Studies on Herqulines and Lycopodium Alkaloids

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With the support of the Chemical Synthesis (SYN) Program in the Division of Chemistry, Professor Dirk Trauner of the University of Pennsylvania is developing new methods and strategies to synthesize alkaloids. Alkaloids are a class of natural products that have played a critical role in the advancement of organic chemistry and pharmacology. They continue to inspire new synthetic chemistry, as new types of alkaloids are found in a variety of biological sources. The Trauner group studies an alkaloid named herquline A, which has been isolated from the fungus Penicillium herquei and characterized as an inhibitor of the H1N1 influenza virus. In parallel to laboratory work, the Trauner group proposes to develop an educational platform for synthetic design, called Denksport ("Brain Sports"): Denksport involves solving a puzzle that centers on a multistep synthesis, usually of a natural product, a drug, or of a designer molecule with interesting physical features. In addition to being an excellent tool for teaching synthetic strategy and retrosynthetic analysis, it familiarizes students with a wide variety of synthetic methods, reaction mechanisms, reagents, and building blocks. It has been made accessible, free of charge, to the chemical community and has been embraced by undergraduate and graduate students from diverse backgrounds who are invited to contribute to this effort.Herquline A has been a challenge to synthetic chemists and has not been made in the laboratory to date. To meet this challenge, the Trauner Group has developed new methodology based on organoboron chemistry that can be used to rapidly establish the carbon skeleton of herquline A. In addition, Trauner's team studies alkaloids that stem from Lycopodium club mosses. These natural products are amongst the most popular synthetic targets due to their attractive molecular architectures, which are often paired with significant bioactivity. The Trauner group will pursue synthetic strategies that mimic biosynthetic patterns to synthesize the Lycopodium alkaloids phlegmadine A, as well as huperphlegmines A and B. New chemical methodologies, such as anionic cyclizations of ynones, will be pursued to reach these goals.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.