Synthesis of Phostones via Phosphono Substituted Metal Allyl Intermediates

密苏里大学圣路易斯分校的Christopher D. spill教授在化学合成项目资助下，正在开发新的碳-碳键形成反应，并将其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，对分子复制、细胞生物化学、细胞信号通路和代谢过程的激活都很重要。这项研究建立在先前基于磷的研究的基础上，开发了新的基于镍的工艺来获取重要的碳支架。该计划的更广泛的影响在于开发有机合成的新工具和培养本科生和研究生。特别强调本科生参与研究，为合成有机化学技术提供坚实的培训。该培训将有助于为美国的制药研究和相关化学工业提供技术工人。智力优势集中在开发基于新型有机磷化学的合成方法上。金属烯丙基中间体来源于环氧乙烯基膦酸盐，1-和2-取代膦-1,3-二烯和膦烯丙基碳酸盐等前体，为立体选择性C-C和c -杂原子成键反应提供了独特的方法。这些反应允许互补的方法来合成具有新的生物学特性并可作为药物化学先导化合物的光子和膦糖。这种从头开始的方法提供了独特的取代模式和立体化学，偏离了容易获得的（常见的）碳水化合物，非常适合合成脂质A的潜在拮抗剂。

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.