Synthetic Studies on Alkaloids Isolated from Lycopodium annotium and a New Synthesis of Tetrodotoxin

石松生物碱的合成研究及河豚毒素的新合成

• 批准号: 1900154
• 负责人: Dirk Trauner
• 金额: $ 48.5万
• 依托单位: New York University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1900154&HistoricalAwards=false
• 关键词: Synthetic; Studies; Alkaloids; Isolated; Lycopodium

With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Dirk Trauner of New York University. Professor Trauner is studying a class of naturally occurring molecules called "alkaloids". These molecules contain nitrogen atoms and have been vital in the discovery of several biological or physiological processes, particularly in the nervous system, and have played important roles as therapeutic drugs. Due to their fascinating chemical structures and biological activities, they have inspired the development of new methods for the synthesis of organic molecules, some of which now play a crucial role in the pharmaceutical industry. They have been a platform to continuously refine tactics and strategies that synthetic chemists employ to synthesize related molecules found in nature. In this proposal, Professor Trauner is preparing several such molecules via routes that mimic their possible synthesis in nature. In addition to synthesizing these molecules, this work is providing a better understanding of the effects of these molecules on their biological targets. Professor Trauner is also engaged in outreach and is a co-organizer of "Entertaining Science," which brings together scientist, artists, and the general public in the Cornelia Street Cate, New York City.Professor Trauner and his team are studying the synthesis of a class of structurally complex alkaloids from the clubmoss Lycopodium annotinum, none of which have been synthesized to date. Members of this class of alkaloids known as the annotinolides and lannotinidines, are being be synthesized through a unified approach that centers on lannotinidine G. Additionally, a new synthesis of tetrodotoxin (TTX), the infamous toxin responsible for the paralytic effects of fugu poisoning, is being studied. Although TTX is a classic target, its synthesis remains a formidable challenge. This approach is improving the state of the art and serving in the development of new TTX derivatives that are being used to study certain voltage gated sodium channels that have relevance to alleviating pain. As a part of this project, Professor Trauner's students are receiving training in chemical synthesis and exposure to neurophysiology, preparing them for careers in chemical and pharmaceutical industries.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.

有了这个奖项，美国国家科学基金会化学部的化学合成计划正在支持纽约大学的Dirk Trauner教授的研究。特劳纳教授正在研究一类称为“生物碱”的天然分子。这些分子含有氮原子，在发现几种生物或生理过程中至关重要，特别是在神经系统中，并且作为治疗药物发挥了重要作用。由于其迷人的化学结构和生物活性，它们激发了有机分子合成新方法的发展，其中一些现在在制药工业中发挥着至关重要的作用。它们一直是一个平台，不断完善合成化学家用来合成自然界中发现的相关分子的战术和策略。在这项提案中，Trauner教授正在通过模拟自然界中可能的合成途径制备几种这样的分子。除了合成这些分子外，这项工作还提供了对这些分子对其生物靶点的影响的更好理解。Trauner教授还从事外展活动，是“娱乐科学”的共同组织者，该活动将科学家、艺术家和公众聚集在纽约市的科尔内利亚街美食餐厅。Trauner教授和他的团队正在研究从石松中合成一类结构复杂的生物碱，迄今为止还没有合成过。这类生物碱的成员被称为annotinolides和lannotinidines，正在通过一个统一的方法，中心lannotinidine G合成。此外，正在研究一种新的河豚毒素（TTX）合成方法，这种臭名昭著的毒素会导致河豚中毒的麻痹效果。虽然TTX是一个经典的目标，其合成仍然是一个艰巨的挑战。这种方法正在改善现有技术，并用于开发新的TTX衍生物，这些衍生物用于研究与缓解疼痛相关的某些电压门控钠通道。作为该项目的一部分，Trauner教授的学生正在接受化学合成和神经生理学方面的培训，为他们在化学和制药行业的职业生涯做好准备。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

A concise synthesis of tetrodotoxin

• DOI: 10.1126/science.abn0571
• 发表时间: 2022-07-22
• 期刊: SCIENCE
• 影响因子: 56.9
• 作者: Konrad, David B.;Ruehmann, Klaus-Peter;Trauner, Dirk
• 通讯作者: Trauner, Dirk