TOTAL SYNTHESIS OF AZASPIRACIDS

氮杂螺酸的全合成

• 批准号: 7082128
• 负责人: K. C. NICOLAOU
• 金额: $ 43.11万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7082128
• 关键词: Bivalvia; analytical method; bioassay; biological products; biotechnology; chemical synthesis; drug discovery /isolation; hybridomas; immunologic assay /test; immunologic substance development /preparation; marine toxins; method development; monoclonal antibody; pharmacokinetics; recombinant proteins; saxitoxin; seafood poisoning; spirane

DESCRIPTION (provided by applicant): This proposal describes a research program directed towards the total synthesis of azaspiracids-l, -2, -3, and -6, and fragments thereof, for biological and analytical purposes. Isolated from the mussel Mytilus edulis, these marine neurotoxins are the causative agents of seafood poisoning in humans and tumorogenesis in rats. These extremely scarce biotoxins have been isolated only in minute quantities and it remains for chemical synthesis to render them available for the acutely needed analytical work to detect and quantify them in seafood before releasing it for human consumption. Considerable progress has been made already by this group, uniquely positioning us to accomplish the efficient total synthesis of all four azaspiracids, develop antibodies against them, and investigate their mechanism of action and full spectrum of biological properties. The latter investigations will be carried out in collaboration with biology experts and are expected to result, in particular, in the development (through antibody production) of a bioassay for the determination of the toxins. The significance of the proposed work lies primarily in improving and assuring environmental health, detecting and measuring marine biotoxins, and cleaning the oceans, as well as to prevent seafood poisoning in humans that may include both short (e.g. nausea, vomiting, severe diarrhea and stomach cramps) and long term (e.g. lung, liver, spleen and lymphocyte damage as well as cancer) health hazards. The project is also expected to advance our knowledge in chemical synthesis and impact favorably the drug discovery and development process.

描述（由申请人提供）：该提案描述了一项针对azaspiracids -l，-2，-3和-6的总合成的研究计划，以及其碎片，用于生物学和分析目的。这些海洋神经毒素是从贻贝mytilus edulis分离出来的，是人类中海鲜中毒的病因和大鼠的肿瘤发生。这些极为稀缺的生物毒素仅以微量的量分离出来，它仍然用于化学合成，以使其可用于急需的分析工作，以在海鲜中检测和量化它们，然后再释放它以供人类食用。该群体已经取得了很大的进步，它使我们定位以实现所有四种偶氮尿素的有效总合成，对它们产生抗体，并研究它们的作用机理和全部生物学特性。后者的研究将与生物学专家合作进行，并有望在生物测定的开发（通过抗体生产）中，以确定毒素。 The significance of the proposed work lies primarily in improving and assuring environmental health, detecting and measuring marine biotoxins, and cleaning the oceans, as well as to prevent seafood poisoning in humans that may include both short (e.g. nausea, vomiting, severe diarrhea and stomach cramps) and long term (e.g. lung, liver, spleen and lymphocyte damage as well as cancer) health hazards.预计该项目还可以提高我们在化学合成方面的知识，并对药物发现和开发过程产生有益的影响。