Synthetic Studies on Herqulines and Lycopodium Alkaloids

在化学系化学合成(SYN)计划的支持下，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起着至关重要的作用。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类型的生物碱。Trauner团队研究了一种名为Herquline A的生物碱，它是从真菌Herquei中分离出来的，被鉴定为H1N1流感病毒的抑制剂。在实验室工作的同时，Trauner小组建议开发一个名为DenkSports(大脑运动)的合成设计教育平台：DenkSports涉及解决以多步骤合成为中心的难题，通常是天然产品、药物或具有有趣物理特征的设计师分子的合成。除了是教授合成策略和逆合成分析的极好工具，它还使学生熟悉各种合成方法、反应机理、试剂和积木。它已经向化学界免费开放，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，到目前为止还没有在实验室生产过。为了迎接这一挑战，Trauner Group开发了基于有机硼化学的新方法，可用于快速建立大黄素A的碳骨架。此外，Trauner的团队还研究了源自石松属球状苔藓的生物碱。这些天然产物是最受欢迎的合成目标之一，因为它们具有诱人的分子结构，通常与显著的生物活性配对。Trauner小组将采用模拟生物合成模式的合成策略来合成石松生物碱、石杉碱甲以及石杉碱胺A和B。为了实现这些目标，将采用新的化学方法，如芳酮的阴离子环化反应。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.