Synthesis of Phostones via Phosphono Substituted Metal Allyl Intermediates

通过膦基取代的金属烯丙基中间体合成膦

• 批准号: 1465196
• 负责人: Christopher Spilling
• 金额: $ 37.67万
• 依托单位: University of Missouri-Saint Louis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1465196&HistoricalAwards=false
• 关键词: Synthesis; Phostones; via; Phosphono; Substituted

AbstractIn this project, funded by the Chemical Synthesis Program of the Chemistry Division, Professor Christopher D. Spilling of the University of Missouri St. Louis is developing new carbon-carbon bond forming reactions with applications in the synthesis of medicinally relevant phosphate-substituted sugars. The phosphate group is a fundamental component of all living systems, and is important for molecular replication, cell biochemistry, cell signalling pathways, and activation in metabolic processes. The research builds on prior phosphorous-based research developing new nickel-based processes to access important carbon scaffolds. The broader impact of this program lies in developing new tools for organic synthesis and the training of undergraduate and graduate students. A particular emphasis is placed on undergraduate participation in research to provide a solid training in the techniques of synthetic organic chemistry. The training will help provide skilled workers to support pharmaceutical research and related chemical industry in the US.The intellectual merit is focused on developing synthetic methods based on new organophosphorous chemistry. Metal allyl intermediates derived from precursors such as epoxy-vinyl phosphonates, 1- and 2- substituted phosphono-1,3-dienes and phosphono allylic carbonates provide unique methods of stereoselective C-C and C-heteroatom bond forming reactions. These reactions allow complimentary approaches to the synthesis of phostones and phosphonosugars that have novel biological properties and may serve as lead compounds for medicinal chemistry. This de novo approach provides phostones with unique substitution patterns and stereochemistry which deviate from the readily available (common) carbohydrates that is ideally suited to the synthesis of potential antagonists of lipid A.

本课题由化学系化学合成项目资助，由美国哈佛大学化学系化学与物理系Christopher D.密苏里州圣路易斯大学的Spilling正在开发新的碳-碳键形成反应，并应用于合成与医学相关的磷酸盐取代糖。磷酸基团是所有生命系统的基本组成部分，并且对于分子复制、细胞生物化学、细胞信号传导途径和代谢过程中的活化是重要的。 该研究建立在先前的磷基研究基础上，开发了新的镍基工艺，以获得重要的碳支架。该计划的更广泛的影响在于开发有机合成的新工具以及本科生和研究生的培训。特别强调本科生参与研究，以提供合成有机化学技术的扎实培训。该培训将帮助提供技术工人，以支持美国的制药研究和相关化学工业。智力优势集中在开发基于新有机磷化学的合成方法。衍生自前体如环氧-乙烯基膦酸酯、1-和2-取代的膦酰基-1，3-二烯和膦酰基烯丙基碳酸酯的金属烯丙基中间体提供了立体选择性C-C和C-杂原子键形成反应的独特方法。这些反应允许互补的方法来合成具有新的生物学特性的磷酮和膦酰糖，并可作为药物化学的先导化合物。 这种从头方法提供了具有独特取代模式和立体化学的phostone，其偏离了理想地适合于合成脂质A的潜在拮抗剂的容易获得的（常见的）碳水化合物。