Development of New Synthetic Methods for the Preparation of Organic Fluorine Compounds and the Application to Fluorinated Biological Substances

1.二氟环丙烷类化合物的不对称合成及其在谷氨酸化学修饰中的应用研究进展在药物化学和材料科学领域中，环丙烷单元的引入是一种重要的分子设计。我们已经开发了有效的方法，用于不对称合成的氟化环丙烷直接对生物重要物质的化学修饰。我们成功地建立了两种方法，即（1）用溴代二氟巴豆酸酯非对映、区域和立体选择性合成功能化的二氟环丙烷和（2）用二氟卡宾加成反应制备手性结构单元。此外，我们还合成了所有可能的（二氟甲烷）谷氨酸酯的立体异构体，并发现了一种新的代谢型谷氨酸受体特异性激动剂.二氟乙烯基醚衍生物的Aldor-type反应研究进展 ...更多信息 阳离子化的二氟酮是一类重要的水解酶抑制剂，我们通过新的活化方法成功地开发了二氟乙烯基醚衍生物与羰基和亚胺化合物的有效羟醛型反应.基于二茂锆化学的合成方法的研究进展在我们正在进行的二茂锆化学研究项目中，我们建立了一种基于二茂锆与乙烯基环丙烷反应的甾体侧链的高效构建方法，并研究了一种基于二茂锆与烷氧基甲基苯乙烯衍生物反应的甾体骨架的快速构建方法.亲电碘化合成新反应的发展作为碘介导活化过程研究项目中的一个有效合成反应，我们建立了N-烯丙基烯酰胺的Diels-Alder反应。此外，我们还成功地在碘代碳环化反应中进行了不对称催化，将我们新发展的茂锆化学和碘介导的反应应用于氟化学是我们正在进行的课题。少

1. Development of Asymmetric Synthesis of Difluorocyclopropanes and Its Application to Chemical Modification of Glutamic AcidIntroduction of cyclopropane unit into a molecule is recognized as an important molecular design in the field of medicinal chemistry and material sciences. We have developed efficient methods for asymmetric synthesis of fluorinated cyclopropanes directed toward chemical modification of biologically important substances. We have successfully established two methods, namely (1) diastereo-, regio- and stereo-selective synthesis of functionalized difluorocyclopropaned using bromodifluorocrotonate and (2) preparation of chiral building blocks using difluorocarbene addition reaction. Furthermore, we have achieved the synthesis of all of the possible stereoisomers of (difluoromethano) glutamates and we have also found a new specific agonit for metabotropic glutamate receptor.2. Development of Aldor-type Reaction of Difluoroviny Ether DerivativesFor the prepartion of fun … More ctionalized difluoroketones, which are classified as important compounds as inhibitors of certain hydrolytic enzymes, we have succeeded in developing efficient aldol-type reactions of difluorovinyl ether derivatives with carbonyl and imine compounds through new activing processes.3. Developments of Synthetic Methods Based on Zirconocene ChemistryIn our ongoing research project on zirconocene chemistry, we have established an efficient method for the construction of steroidal side chain based on the reaction of zirconocene with vinylcyclopropane, and we have also studied a short-step construction of steroidal skeleton based on the reaction of zirconocene and alkoxymethylated stirene derivatives.4. Development of New Synthetic Reactions Through Electrophilic IodinationAs an efficient synthetic reaction related to our research project on iodine-mediated activaing process, we have established Diels-Alder reaction of N-allylic enamides. Furthermore, we have succeeded in asymmetric catalysis of our iodocarbocyclization reaction.Application of our newly developed zirconocene chemistry and iodine-mediated reactions to fluorine chemistry ia our ongoing subject. Less