Enantioselective Organic Syntheses (Chemistry)

对映选择性有机合成（化学）

• 批准号: 8704178
• 负责人: Gary Molander
• 金额: $ 17.53万
• 依托单位: University of Colorado at Boulder
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8704178&HistoricalAwards=false
• 关键词: Enantioselective; Organic; Syntheses; Chemistry

The continuing challenge in the area of organic synthesis is to develop synthetic reactions that have generality, yet exhibit great selectivity. Dr. Molander has discovered a way to take an old reaction, the so-called Reformatsky reaction, and greatly increase its usefulness in the synthesis of complex natural products like the beta-lactam antibiotics. This project is in the Organic and Macromolecular Chemistry Program. This will develop novel entries into complex, enantiomerically pure organic substrates. The first aspect of the research will explore use of samarium diiodide-induced intramolecular Reformatsky reactions. Full development of this methodology will permit access to syn 1,3-diols by 1,3-asymmetric induction in a carbon-carbon bond-forming process. Facile generation of HMG-CoA reductase inhibitors is one of many important contributions that this advancement will permit. Application to nitrogen-containing substrates is also planned, and important new routes to pharmacologically important aminoglycoside and beta-lactam antibiotics will result from this aspect of the study. Chemistry based upon samarium diiodide reduction of vinyl oxiranes comprises the second aspect of the study. Allylic alcohols generated by this process will be incorporated into several natural products syntheses, including leukotriene B4. Another unique method for 1,3-asymmetric induction is planned, involving intramolecular Michael addition of samarium-based Reformatsky reagents to conjugated olefins. A novel cyclopropanation reagent, Sm/CH2I2, will be thoroughly studied to determine its unique role in organic synthesis, utilizing allylic alcohols as substrates in the first aspect of studies in this area. Stereocontrolled cyclizations onto chiral epoxides constitute another proposed approach to chiral carbocycles and heterocyclic substrates. Reactions utilizing alkynylborates and allylsilanes will be explored to provide access to organic molecules in which up to three contiguous stereocenters are controlled in a completely predictable fashion. Finally, the chemistry of epoxy anions will be explored. These unique nucleophiles may very well revolutionize the manner in which the versatile epoxide functional group is incorporated into organic molecules.

有机合成领域的持续挑战是 开发具有普遍性的合成反应，但表现出 选择性强。 莫兰德博士发现了一种方法 一种古老的反应，即所谓的Reformatsky反应， 大大提高了其在合成配合物中的有用性 天然产物如β-内酰胺类抗生素。 这 该项目是在有机和高分子化学程序。 这将开发新的条目到复杂的，对映体 纯有机基质。 研究的第一个方面将 探索利用二碘化钐诱导分子内 Reformatsky反应 充分发展这一方法 将允许通过1，3-不对称诱导获得顺式1，3-二醇 在碳-碳键形成过程中。 轻松生成 HMG-CoA还原酶抑制剂是许多重要的 这一进步将允许的贡献。 应用 含氮基质也计划， 重要的新路线 氨基糖苷类和β-内酰胺类抗生素将导致 这方面的研究。 基于二碘化钐还原乙烯基的化学 环氧乙烷是本研究的第二个方面。 烯丙基 由该过程产生的醇将被并入 几种天然产物的合成，包括白三烯B4。 计划另一种独特的1，3-不对称诱导方法， 涉及钐基的分子内迈克尔加成 Reformatsky试剂转化为共轭烯烃。 一种新型 环丙烷化试剂Sm/CH_2 I_2将被深入研究 确定其在有机合成中的独特作用，利用 在第一个方面的研究中， 在这一地区。 在手性环氧化物上的立体控制环化构成 另一种提出的手性碳环的方法， 杂环底物。 利用炔基硼酸酯的反应 和烯丙基硅烷将被探索， 分子中最多有三个连续的立体中心 以完全可预测的方式控制。 最后，将探索环氧阴离子的化学。 这些 独特的亲核试剂可能会彻底改变 其中引入了多功能环氧官能团 转化成有机分子