权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

CAREER: Developing a modular synthesis of 6-7-5 terpenoid natural products and analogs

职业：开发 6-7-5 萜类天然产物和类似物的模块化合成

基本信息

批准号：
1844443
负责人：
Alexander Grenning
金额：
$ 67.5万
依托单位：
University of Florida
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：
2019-05-15 至 2024-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1844443&HistoricalAwards=false
关键词：
CAREER Developing modular synthesis terpenoid

项目摘要

With this CAREER Award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Alexander J. Grenning at the University of Florida. His group is streamlining how bioactive terpenoid natural products, organic molecules commonly derived from plants with important biological activity, are prepared in the laboratory. There are several reasons why this modern challenge needs to be addressed: first, nature often only produces minute quantities of natural products and significant amounts of the chemical are needed for study and use in society. From a given natural product, a limited set of similar compounds can be prepared via what chemists call "semi-synthesis". Semi-synthesis refers to specific limited changes to a natural product. When performing studies designed to understand the way these molecules interact with biological systems, access to a variety of similar compounds is crucial for understanding and improving the reactivity of the parent molecule. Second, the laboratory synthesis of highly complex molecules ("total synthesis") forming large quantities in efficient ways is inherently challenging. Although targeted for decades, there are few general strategies to make the complex terpene molecules. The Grenning lab is studying the laboratory terpene synthesis to better understand the function of this molecule in the body and to enable the advanced manufacturing of the best molecules in large quantities. Educational aspects of this project are aimed at informing the public about the natural products. The Grenning lab is designing freely available "infographics" on terpenes for distribution to the general public. The Grenning lab is also organizing events and conferences ranging from the "Chemathon," a day-long celebration of chemistry for high-school students, to the "Florida Heterocyclic and Synthetic Conference (FloHet)," a specialized international meeting that gathers synthetic organic chemistry leaders to disseminate their research findings. Additional benefits include the recruitment of underrepresented groups, both at the undergraduate and graduate student level, for participation in the projects outlined in this CAREER Award.The Grenning lab is focusing on the synthesis of polycycloalkane natural products bearing tricyclic motifs. This is a common terpenoid architecture that is difficult to access due to its inherent structural complexity. Ketones, malonic acids, and allylic electrophiles serve as starting materials and through an operationally simple and generalized reaction sequences consisting of deconjugative allylations, sigmatropic rearrangements, and ring-closing metathesis, a variety of "terpene scaffolds" are accessible. These terpene scaffolds then serve as platforms for reaction development aimed at preparing terpenoid targets and target-analogs. Select molecules are subject to biological evaluation to validate our chemical advancements. The molecules targeted include the tigliane, daphnane and rhamnofolane families of natural products and their analogs. Broader Impacts include the increased interaction with Santa Fe Community College. By educating the local community on organic chemistry and natural products, Professor Grenning and his group create a dialogue and inspire students to consider careers in chemistry. The team also designs terpenoid infographics and organizes events and conferences for educating students and disseminating results.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.

凭借这一职业奖，美国国家科学基金会化学部的化学合成项目正在支持佛罗里达大学 Alexander J. Grenning 教授的研究。他的团队正在简化生物活性萜类天然产物（通常源自具有重要生物活性的植物的有机分子）在实验室中的制备方法。需要解决这一现代挑战的原因有几个：首先，大自然通常只生产微量的天然产物，而社会研究和使用需要大量的化学物质。从给定的天然产物中，可以通过化学家所谓的“半合成”制备有限的一组类似化合物。半合成是指对天然产物进行特定的有限改变。当进行旨在了解这些分子与生物系统相互作用的方式的研究时，获得各种类似的化合物对于了解和提高母体分子的反应性至关重要。其次，实验室合成高度复杂的分子（“全合成”）以有效的方式形成大量的本质上具有挑战性。尽管几十年来一直有目标，但制造复杂萜烯分子的通用策略却很少。格伦宁实验室正在研究实验室萜烯合成，以更好地了解这种分子在体内的功能，并能够以先进的方式大批量生产最好的分子。该项目的教育方面旨在让公众了解天然产品。格伦宁实验室正在设计免费提供的萜烯“信息图表”，以分发给公众。格林宁实验室还组织各种活动和会议，从“Chematon”（为高中生举办的为期一天的化学庆祝活动）到“佛罗里达杂环和合成会议（FloHet）”，这是一个聚集合成有机化学领导者来传播他们的研究成果的专门国际会议。其他好处包括招募本科生和研究生级别的代表性不足的群体参与本职业奖中概述的项目。格伦宁实验室专注于合成带有三环基序的多环烷天然产物。这是一种常见的萜类结构，由于其固有的结构复杂性而难以获得。酮、丙二酸和烯丙基亲电子试剂作为起始材料，通过由解共轭烯丙基化、σ重排和闭环复分解组成的操作简单且通用的反应序列，可以获得各种“萜烯支架”。然后，这些萜烯支架充当反应开发的平台，旨在制备萜类靶标和靶标类似物。选择分子进行生物学评估，以验证我们的化学进步。目标分子包括天然产物的替利亚烷、瑞香和鼠李叶烷家族及其类似物。更广泛的影响包括增加与圣达菲社区学院的互动。通过对当地社区进行有机化学和天然产品方面的教育，格伦宁教授和他的团队建立了对话并激励学生考虑化学职业。该团队还设计萜类信息图表，并组织活动和会议来教育学生和传播结果。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。