Total Synthesis of [15N] - Cylindrospermopsin for Monitoring Fresh Water Safety

[15N]-圆柱精蛋白的全合成用于监测淡水安全

• 批准号: 9043894
• 负责人: Armen Zakarian
• 金额: $ 7.68万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9043894
• 关键词: Agriculture; Alkenes; Biological Assay; Chemistry; Complex; Cyanobacterium; Detection; Development; Environment; Eutrophication; Exposure to; Fresh Water; Goals; Health; Human; Industry; Isotopes; Label; Lead; Letters; Link; Measurement; Methods; Monitor; Natural Products; Pharmacologic Substance; Preparation; Process; Production; Reporting; Route; Safety; Science; Seafood; Source; Temperature; Toxin; United States Environmental Protection Agency; Water; chemical synthesis; cylindrospermopsin; feeding; hepatotoxin; liver injury; materials science; stable isotope; tool

 DESCRIPTION (provided by applicant): Cylindrospermopsin is a potent hepatotoxin produced by freshwater cyanobacteria. Blooms of cyanobacteria have recently increased dramatically, likely due to the rise in global temperatures and eutrophication. Release of the toxin into water that is subsequently ingested can lead to liver damage, potentially fatal. Monitoring the levels of cylindrospermopsin (CYN) in freshwater has become a human health issue, and is a subject of recent reports by the US Environmental Protection Agency and USDA. The problem is that accurate quantitative measurements of CYN concentration requires pure, isotopically labeled analytical standards, which can be used in isotope dilution mass-spectrometric assays. Producing this standard from cultures of cyanobacteria using feeding with labeled additives proved to be tedious, unreliable, and lengthy (over 2 years before results are known) process. This project proposes to access the analytical standard by total chemical synthesis, which holds a promise as a reliable source of the much-needed material. Our lab has a strong expertise in producing isotopically labeled complex molecules, including natural products, by total synthesis.

 描述（由适用提供）：胞体性乳蛋白是淡水蓝细菌产生的潜在肝毒素。蓝细菌的开花最近急剧增加，这可能是由于全球温度和富营养化的升高所致。随后摄入的毒素将毒素释放到水中会导致肝损害，可能致命。监视 淡水中的cylindrospermopsin（CYN）已成为人类健康问题，并且是美国环境保护局和USDA最近报告的主题。问题在于，CYN浓度的准确定量测量需要纯，同位素标记的分析标准标准，该标准可以用于同位素稀释的质谱测定法。用标记的添加剂从蓝细菌培养物中产生这种标准，这被证明是乏味，不可靠和冗长的（在结果已知2年以上）过程。该项目的建议是通过总化学合成来访问分析标准的建议，该合成作为急需材料的可靠来源的承诺。我们的实验室在通过总合成中产生包括天然产物在内的同位素标记的复杂分子方面具有强大的专业知识。