Biomimetic Synthesis of Fused Polycyclic Ethers

稠合多环醚的仿生合成

• 批准号: 0516793
• 负责人: Frank McDonald
• 金额: $ 39万
• 依托单位: Emory University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0516793&HistoricalAwards=false
• 关键词: Biomimetic; Synthesis; Fused; Polycyclic; Ethers

This project addresses the biomimetic syntheses of fused polycyclic ethers produced in toxic "red tide" phenomena. Although biosynthetic pathways for these structurally complex compounds have not been completely elucidated, fused polycyclic ether structures are presumed to arise from regioselective and stereospecific tandem oxacyclizations of polyepoxide compounds arising from relatively simple acyclic polyene precursors. This project will focus on mimicking these biosynthetic oxacyclizations in the synthesis of hemibrevetoxin B and a newly discovered pentacyclic natural product, brevenal. Brevenal is of particular interest, as it is a nontoxic, competitive inhibitor for the neurotoxic activity of other fused polycyclic ethers such as brevetoxin B. Isotopically labelled polyenes corresponding to the possible biogenetic precursors of both natural products will also be synthesized. In collaborative work, these polyenes and derived polyepoxides will be studied in feeding experiments with cultures of Karenia brevis, the organism responsible for the red tide and associated production of fused polycyclic ether natural product toxins.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Frank E. McDonald of the Department of Chemistry at Emory University. Professor McDonald and his students are exploring the synthesis of toxins produced in "red tide" phenomena, responsible for fish kills along the Atlantic and Gulf Coast areas of the southeastern United States and producing neurotoxic symptoms in humans when contaminated fish are ingested. Their syntheses are designed to mimic the synthetic routes used by Nature, and include studies of a newly discovered natural product, brevenal, which serves as a nontoxic, competitive inhibitor for the neurotoxic activity of other red tide toxins. Professor McDonald's studies will shed light on the fundamental processes responsible for the biological synthesis of complex toxins. In addition, they promise impacts in the development of potential treatments for red tide toxicity, of value in the case of toxicity due to aerosol formation by natural wave action as well as intentional delivery of red tide toxins.

该项目介绍了在有毒“红潮”现象中产生的融合多环醚的仿生合成。尽管这些结构复杂化合物的生物合成途径尚未完全阐明，但假定融合的多环状醚结构是由多环氧化物化合物的区域选择性和立体特异性的串联氧化物产生的，这些氧化化合物是由相对简单的acyclicclic comclic comclic comclic comclic comyclic ocyclic compliens产生的。该项目将着重于模仿半赤毒素B的合成和新发现的五环天然产品Brevenal中的这些生物合成氧化。对于其他融合多环乙醇（如Brevetoxin B.）的神经毒性活性，Brevenal是一种尤其令人感兴趣的竞争性抑制剂B。同位素标记的多烯元素，与两种天然产物的可能生物遗传学前体相对应。 In collaborative work, these polyenes and derived polyepoxides will be studied in feeding experiments with cultures of Karenia brevis, the organism responsible for the red tide and associated production of fused polycyclic ether natural product toxins.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Frank E. McDonald of the Department of Chemistry at Emory University.麦当劳教授和他的学生正在探索“红潮”现象中产生的毒素的综合，该现象是导致美国东南部大西洋和墨西哥湾沿岸地区杀死鱼类的杀菌，并在被污染的鱼类时在人类中产生神经毒性症状。它们的合成旨在模仿自然所使用的合成路线，并包括对新发现的天然产物Brevenal的研究，该产品可作为其他红潮毒素神经毒性活性的无毒的竞争性抑制剂。麦当劳教授的研究将阐明负责复杂毒素生物合成的基本过程。此外，它们有望在发育红潮毒性的潜在治疗方法上产生影响，在毒性的情况下，由于天然波动作用以及有意递送红潮毒素而导致的毒性。