Development of Practical Electrolytic Partial Fluorination Processes of Heterocyclic Compounds Towards Biological Activities

点击翻译按钮获取中文摘要

Since introduction of fluorine atom (s) into organic molecules sometimes enhances markedly their biological activities, the development of efficient direct fluorination methods has been becoming increasingly important. However, selective direct fluorination has been underdeveloped so far owing to lack of selectivity, the low nucleophilicity of fluoride ions, and passivation of the anode. Although many heterocyclic compounds possess biological activities, there have been few examples of their successful selective fluorinations. On the other hand, we have shown that an anodic method is a quite powerful for the selective direct fluorination of various heteroatom compounds such as sulfides.From these view points, we have developed highly efficient and safe methods for selective anodic partial fluorination of various heterocycles towards bioligical activities as follows. 1) Development of Fluorinated Supporting Electrolytes and Clarification of Their Electrochemical Properties : Since fluor … More ide salts as a supporting electrolyte greatly affect anodic fluorination, we developed entirely new types of fluorinated supporing electrolytes and clarified their electrochemical properties such as potential windows. 2) Selective Anodic Monofluorination of Sulfur-containing Heterocycles : Electroplyutic conditions for anodic monofluorination of various sulfur-containing heterocycles such as thiolanones, oxathiolanones, dithiolanones, and 3H-1,4-benzooxathian-2-ones were optimized using various supporting fluoride salts in order to establish the highly efficient anodic fluorination method. 3) Direct Anodic Monofluorination of Nitrogen-containing Heterocycles : Electrolytic conditions for anodic monofluorination of various nitorgen-containing heterocycles such as oxindoles and tetrahydroisoquinolines were optimized using various anode materials and fluoride supporting electrolytes. 4) Indirect anodic monofluorodesulfurization of beta-phenylsulfenyl beta-lactams was successfully performed by using a catalytic amount of triarylamine mediators. 5) Screening test of biological activities of anodically fluorinated heterocycles was done and fluorothiolanones were found to show strong PLA2 inhibitory activity.Thus, we have demonstrated that our develped electrolytic fluorination can be widely applicable and should be a versatile process for manufacturing various types of biologically active heterocyclic compounds. Less