Synthesis of Marine Neurotoxins

海洋神经毒素的合成

• 批准号: 7821404
• 负责人: K. C. NICOLAOU
• 金额: $ 44.73万
• 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/7821404
• 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）：本提案描述了一个研究项目，旨在通过化学合成解决关于海洋神经毒素maitotoxin结构的立体化学争议，缺乏侧链的maitotoxin的截断版本的全合成，maitotoxin的全合成，以及用于分析和生物学研究的适合maitotoxin样结构的抗体的开发。这个化学合成计划的不断升级的挑战将通过一个融合的策略来满足，包括在这个和其他实验室开发的方法。合成方案的特点是基于烯烃复分解的碳-碳键形成反应，新的不对称过程和环闭合。将对合成的截断的maitotoxin样分子进行生物活性测试，开发的抗体将用于maitotoxin的检测和测量以及进一步的生物学研究。该计划还有望产生重要的新合成策略和技术，用于更广泛的药物发现和开发过程，特别是适合药物研究的小对映体纯构建块的合成。总的来说，拟议工作的意义在于改善和确保环境健康，检测和测量海洋神经毒素，清洁海洋，以及防止人类因食用海产品而中毒。该项目还有望大大提高我们在化学合成、化学生物学和医学方面的知识