Synthetic Studies on Herqulines and Lycopodium Alkaloids

在化学系化学合成（SYN）项目的支持下，宾夕法尼亚大学的Dirk Trauner教授正在开发合成生物碱的新方法和策略。生物碱是一类天然产物，在有机化学和药理学的发展中发挥了关键作用。它们继续激发新的合成化学，因为在各种生物来源中发现了新型生物碱。特劳纳研究小组研究了一种名为herquline A的生物碱，它是从真菌Penicillium herquei中分离出来的，其特征是H1N1流感病毒的抑制剂。在实验室工作的同时，Trauner小组建议开发一个合成设计的教育平台，称为Denksport（“大脑运动”）：Denksport涉及解决一个以多步合成为中心的难题，通常是天然产品，药物或具有有趣物理特征的设计师分子。除了是一个很好的工具，用于教学合成策略和逆合成分析，它使学生熟悉各种各样的合成方法，反应机理，试剂和积木。化学界可以免费获得它，并受到来自不同背景的本科生和研究生的欢迎，他们被邀请为这一努力做出贡献。Herquline A对合成化学家来说是一个挑战，迄今为止还没有在实验室中制造出来。为了应对这一挑战，特劳纳集团开发了基于有机硼化学的新方法，可用于快速建立Herquline A的碳骨架。 此外，特劳纳的研究小组还研究了石松中的生物碱。这些天然产物是最受欢迎的合成靶标之一，因为它们具有吸引人的分子结构，通常与显着的生物活性配对。特劳纳研究小组将采用模拟生物合成模式的合成策略，合成石松属生物碱曲马定A以及石杉碱A和B。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.