Development of new synthetic methods for organofluorine compounds of biomedical interest

随着我们不断研究开发新的有机氟化合物合成方法，以合成具有生物医学意义的化合物的氟类似物，我们在这三年中重点开发了立体选择性构建氟化烯烃、碳环化合物和环丙烷羧酸衍生物的有效方法，部分资金来自教育、科学、体育和文化部。现将氟化学方面的研究成果总结如下。(1)建立了具有合适官能团和取代基的(Z)-氟烯烃衍生物的立体选择性结构，可作为二肽同位异构体应用。(2)我们开发了末端二氟化烯基活性甲基化合物的碳环化反应，得到了氟化功能化的五元碳环化合物。(3)成功建立了两步立体选择性合成氟环丙烷羧酸衍生物的方法。此外，我们的研究项目还包括开发非氟有机化合物的高效合成方法，这些方法由于其通用性，未来可以应用于氟化合物的制备。这些反应包括纯烯丙基活性甲基自由基和偶氮纯烯丙基自由基与各种烯烃的自由基[3+2]环加成反应生成相应的环化合物，以及锆介导的n-烯基氨基甲酸酯衍生物的烯烃-羰基偶联反应制备氨基酸和含氮杂环化合物。

As our continuous studies on development of new synthetic methods for organofluorine compounds directed to the synthesis of fluoro analogs of biomedically interesting compounds, we have focused to develop efficient methods for stereoselective construction of fluorinated olefins, carbocyclic compounds and cyclopropane carboxylic acid derivatives during these three years with the financial support in part from the Ministry of Education, Science, Sports and Culture. Our achievements in fluorine chemistry are summarized as follows. (1)Stereoselective construction of (Z)-fluoroolefin derivatives having an appropriate functional groups and substituents, which can be applied as dipeptide isosteres can be established. (2)We have developed carbocyclization reaction of terminally difluorinated alkenyl active methine compounds leading to fluorinated functionalized five membered carbocylic compounds. (3)A two step stereoselective synthesis of fluorocyclopropane carboxylic acid derivatives was successfully established. Moreover, development of highly efficient synthetic methods for nonfluorinated organic compounds, which, due to their generality, could be applied to the preparation of fluorinated compounds in the future is also involved in our research project. These are radical [3+2] cycloaddition reactions of homoallyl active methine radical species and azahomoallyl radical species with various alkenes leading to the coresponding cyclic compounds, and zirconium mediated olefin-carbonyl coupling reaction of N-alkenylcarbamate derivatives for the preparation of amino acids and nitrogen containing heterocyclic compounds.