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

1.不对称合成二氟环丙烷的进展及其在谷氨酸化学修饰中的应用在药物化学和材料科学领域，将环丙烷单元引入分子被认为是一种重要的分子设计。我们开发了高效的不对称合成含氟环丙烷的方法，用于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)用溴二氟代环丙酸盐非对映、区域和立体选择性地合成功能化的二氟环丙烷；(2)用二氟卡宾加成反应制备手性构筑块。此外，我们还合成了(二氟甲基)谷氨酸的所有可能的立体异构体，并发现了一种新的代谢型谷氨酸受体的特异性激动剂。二氟乙烯醚衍生物制备FUN-…的Aldor型反应研究进展更多的阳离子化的二氟酮类化合物被归类为某些水解酶的重要抑制剂，我们通过新的活化工艺成功地开发了二氟乙烯基醚衍生物与羰基和亚胺类化合物的高效羟醛缩合反应。基于茂锆化学的合成方法进展在我们正在进行的茂锆化学研究项目中，我们已经建立了一种基于茂锆与乙烯基环丙烷反应的有效的构筑甾体侧链的方法，并研究了一种基于茂锆与烷氧甲基化的斯蒂衍生物反应的快速构筑甾体骨架的方法。亲电碘化合成新反应的研究进展作为一种有效的合成反应，我们建立了N-烯丙基烯丙基酰胺的Diels-Alder反应，该反应与我们的碘介导活化过程研究项目有关。此外，我们还成功地完成了我们的不对称催化的碘化碳环化反应。我们正在进行的课题是将我们新开发的新发展的二茂铁化学和碘介导的反应应用到氟化学中。较少

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