Development of new synthetic methods for organofluorine compounds of biomedical interest

随着我们不断研究开发有机氟化合物的新合成方法，以合成具有生物医学价值的化合物的氟类似物为目标，我们在这三年中一直致力于开发高效的方法来立体选择性地构建含氟烯烃、碳环化合物和环丙烷羧酸衍生物，部分资金来自文部科学、体育和文化部。我们在氟化学方面的成就概括如下。(1)可以建立具有适当官能团和取代基的(Z)-氟烯烃衍生物的立体选择性结构，这些衍生物可以用作二肽等位体。(2)我们对末端二氟的烯基活性亚甲基化合物进行了碳环化反应，得到了含氟化的五元碳环化合物。(3)建立了氟环丙烷羧酸衍生物的两步立体选择性合成方法。此外，我们的研究项目还包括开发高效的非氟有机化合物的合成方法，由于它们的通用性，可以应用于未来的含氟化合物的制备。它们是高烯丙基活性亚甲基自由基物种和氮杂高烯丙基自由基物种与不同烯烃的自由基[3+2]环加成反应，得到相应的环状化合物，以及锆催化的N-烯基氨基甲酸酯衍生物的烯烃-羰基偶联反应，以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.