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

 描述（由申请人提供）：金藻毒素是一种由淡水蓝藻产生的强效肝毒素。蓝藻水华最近急剧增加，可能是由于全球气温上升和富营养化。毒素释放到水中，随后被摄入可能导致肝脏损伤，可能致命。监测 淡水中的柱孢菌素（CYN）已经成为人类健康问题，并且是美国环境保护署和美国农业部最近报告的主题。问题是CYN浓度的精确定量测量需要纯的同位素标记的分析标准品，其可用于同位素稀释质谱测定。使用标记的添加剂从蓝细菌培养物中生产本标准品被证明是繁琐、不可靠和漫长的（在结果已知之前超过2年）过程。该项目建议通过全化学合成获得分析标准品，这有望成为急需材料的可靠来源。我们的实验室在通过全合成生产同位素标记的复杂分子（包括天然产物）方面拥有强大的专业知识。

 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.