Enantioselective Organic Syntheses (Chemistry)

有机合成领域的持续挑战是开发既具有普遍性又表现出很高选择性的合成反应。莫兰德博士发现了一种方法，可以利用一种古老的反应，即所谓的雷格茨基反应，并极大地提高其在合成β-内酰胺类抗生素等复杂天然产物中的有用性。该项目在有机化学和高分子化学项目中。这将开发新的进入复杂的，对映体纯的有机底物。研究的第一个方面将探索使用二碘化钐诱导的分子内重排反应。这一方法的全面发展将允许在碳-碳键形成过程中通过1，3-不对称诱导获得1，3-二醇。HMG-CoA还原酶抑制剂的简便易行的产生是这一进步将允许的许多重要贡献之一。还计划在含氮底物上应用，这方面的研究将产生重要的药理作用的氨基糖苷类和β-内酰胺类抗生素的重要新路线。这项研究的第二个方面是基于二碘化钐还原环氧乙烷的化学。通过这个过程产生的烯丙醇将被加入到几种天然产物的合成中，包括白三烯B4。另一种独特的1，3-不对称诱导方法正在计划中，包括分子内Michael加成，基于钐的Reformsky试剂与共轭烯烃的加成。一种新的环丙烷化试剂Sm/CH2I2将被深入研究，以确定其在有机合成中的独特作用，在这一领域的第一个方面的研究是以烯丙醇为底物。在手性环氧化物上的立体控制环化反应构成了另一种合成手性碳环和杂环底物的方法。将探索利用炔基硼酸盐和烯丙基硅烷进行的反应，以提供接触有机分子的途径，其中最多三个连续的立体中心以完全可预测的方式进行控制。最后，对环氧阴离子的化学进行了探讨。这些独特的亲核试剂可能会很好地改变将多功能环氧化物官能团结合到有机分子中的方式。

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.