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

杂环化合物实用电解部分氟化工艺的开发以实现生物活性

基本信息

批准号：
07555278
负责人：
FUCHIGAMI Toshio
金额：
$ 3.33万
依托单位：
Tokyo Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

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

由于在有机分子中引入氟原子有时会显着提高其生物活性，因此开发高效的直接氟化方法变得越来越重要。然而，由于选择性差、氟离子亲核性低以及阳极钝化等原因，选择性直接氧化法一直不太成熟。虽然许多杂环化合物具有生物活性，但它们成功的选择性氟化的例子很少。另一方面，我们已经证明，阳极方法是一个相当强大的选择性直接取代的各种杂原子化合物，如硫化物。从这些观点来看，我们已经开发出高效和安全的方法，选择性阳极部分取代的各种杂环生物活性如下。1)含氟支持电解质的研究进展及其电化学性质的阐明 ...更多信息由于氟化盐作为支持电解质对阳极氧化有很大影响，我们开发了全新的氟化氧化电解质，并阐明了它们的电化学性能，如电位窗口。2)含硫杂环化合物的选择性阳极氧化：以不同的氟盐为载体，优化了硫杂环化合物如硫杂环酮、氧硫杂环酮、二硫杂环酮和3 H-1，4-苯并氧硫杂环-2-酮的阳极氧化条件，建立了高效的阳极氧化方法。3)含氮杂环化合物的直接阳极单氧化：使用各种阳极材料和氟化物支持电解质优化了各种含氮杂环化合物如羟吲哚和四氢异喹啉的阳极单氧化的电解条件。4)通过使用催化量的三芳胺介体，成功地进行了β-苯硫基β-内酰胺的间接阳极单氟脱硫。5)对阳极氟化杂环化合物的生物活性进行了筛选试验，发现氟硫杂环酮类化合物具有很强的PLA 2抑制活性，从而证明了我们开发的电解法具有广泛的应用前景，是一种生产各种生物活性杂环化合物的通用工艺。少