Synthesis of Marine Neurotoxins

海洋神经毒素的合成

• 批准号: 7626848
• 负责人: K. C. NICOLAOU
• 金额: $ 51.76万
• 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 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7626848
• 关键词: Alkenes; Antibodies; Biological; Biological Testing; Biology; C-glycoside; Carbon; Chemicals; Consumption; Detection; Development; Environmental Health; Human; Investigation; Knowledge; Laboratories; Marines; Measurement; Measures; Medicine; Methods; Neurotoxins; Oceans; Pharmacologic Substance; Poisoning; Process; Pyrans; Radioimmunoassay; Reaction; Research; Resolution; Scheme; Seafood; Side; Structure; Technology; Work; base; chemical synthesis; drug discovery; improved; maitotoxin; meetings; novel; prevent; programs; stereochemistry

DESCRIPTION (provided by applicant): This proposal describes a research program directed towards resolving a stereochemical controversy over the structure of the marine neurotoxin maitotoxin through chemical synthesis, the total synthesis of a truncated version of maitotoxin lacking the side chains, the total synthesis of maitotoxin, and the development of antibodies of suitable maitotoxin-like structures for analytical and biological studies. The escalating challenges of this chemical synthesis program will be met by a convergent strategy involving methods developed in this and other laboratories. Featured in the synthetic plans are olefin metathesis- based carbon-carbon bond forming reactions, novel asymmetric processes and ring closures. Synthetic truncated maitotoxin-like molecules will be tested for biological activity and developed antibodies will become available for the detection and measurement of maitotoxin and further biological studies. The proposed program is also expected to yield significant new synthetic strategies and technologies for broader applications in the drug discovery and development process, particularly for the synthesis of small enantiomerically pure building blocks suitable for pharmaceutical research. Overall the significance of the proposed work lies in improving and assuring environmental health, detecting and measuring marine neurotoxins and cleaning the oceans, as well as to prevent human poisoning through seafood consumption. The project is also expected to significantly advance our knowledge in chemical synthesis, chemical biology, and medicine

描述（由申请人提供）：该提案描述了一项研究计划，旨在解决通过化学合成的海洋神经毒素大毒素的结构，这是截断的Maitotoxin截断版本缺乏侧链缺乏侧链的截断版本的总合成的总体合成，该链链缺乏抗体毒素和抗生素的发展的总合成。该化学综合计划的不断挑战将通过涉及在该实验室和其他实验室中开发的方法的收敛策略来应对。合成计划中的特征是基于烯烃的碳碳键形成反应，新型的不对称过程和环闭环。合成的截短的大毒素样分子将进行生物学活性测试，并且开发的抗体将用于检测和测量Maitotoxin和进一步的生物学研究。预计该计划还将在药物发现和开发过程中更广泛的应用产生重要的新合成策略和技术，尤其是用于合成适合药物研究的小型对映体纯粹的构建模块。总体而言，提出的工作的重要性在于改善和确保环境健康，检测和测量海洋神经毒素并清洁海洋，并通过消耗海鲜来防止人类中毒。预计该项目将大大提高我们在化学合成，化学生物学和医学方面的知识