Development of Novel Sythesis and Molecular Design of Biologically Active Fluorine Compounds Using Electrode Electron-Transfer Reactions

利用电极电子转移反应开发生物活性氟化合物的新型合成和分子设计

• 批准号: 04650765
• 负责人: FUCHIGAMI Toshio
• 金额: $ 1.34万
• 依托单位: Tokyo Institute of Techology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04650765/
• 关键词: Monofluoro beta-lactam; 4-Thiazolidinone; Biologically active compounds; Regioselectivity; Anodic oxidation; Organic electrochemistry; Fiuoroheterocycles; Chiral compounds; 部分フッ素化; 陽極酸化; 有機電気化学; フッ素化合物; モノフルオロβーラクタム

Methods of direct fluorination and mlecular conversion for the development of biologically active fluorine compounds have many roblems in the safety, selectivity, and efficiency. From this point, we have developed very efficient methods of the preparation of fluorine-containing beta-lactams via anodic fluorination as a key step.1. Highly Regioselective Anodic Monofluorination of 4-Thiazolidinones and Its Application to the Synthesis of Monofluoro beta-Lactams : We have successfully carried out efficient and reioselective monofluorination of 4-thazolidinones (1) by the anodc oxidation of 1 in the presence of fluoride ions. This is the first successful example of anodic fluorination of sulfur-containing heterocycles. It was found that thermolysis of the sulfones derived from fluorinated 1 provided monofluoro beta-lactams in excellent yields.2. Regoselective Anodic Monofluorination of beta-Lactams : We have successfully performed anodc partial fluorination of beta-lactams for the first time. It was found that alpha-phenylsulfenyl beta-lactams were monofluorinated highly regioselectively in excellent yields and with high current efficiencies. We have shown that this new anodic method is superior to conventional chemical methods. Thus, we ave almost achieved our roposed projects.

直接氟化和细胞转化的方法用于生物活性氟化合物的开发具有许多在安全性，选择性和效率方面的棘突。从这一点开始，我们已经开发了非常有效的方法，可以通过阳极氟化作为关键步骤制备含氟β-内酰胺的方法1。高度区域性选择性的4-噻唑烷酮及其在单氟β-内酰胺的合成中的应用：我们通过在氟化物的存在下成功地实现了1-替代性的4-替代性单氟化（1）。这是含硫的杂环的阳极氟化的第一个成功例子。发现源自氟化1的硫酮的热解提供了良好产量的单氟β-内酰胺。2。 β-内酰胺的重新选择性阳极单荧光：我们首次成功地对β-内酰胺进行了部分氟化。发现α-苯基磺酰基β-内酰基酰基酰基酰基甲酰胺酰基是单氟二氟的，具有优异的产率和高电流效率。我们已经表明，这种新的阳极方法优于常规化学方法。因此，我们几乎实现了我们的绳索项目。

项目成果

成塚 智: "Electrolytic Partial Fluorination of Organic Compounds.8.Highly Regioselective Anodic Monofluorination of β-Lactams" The Journal of Organic Chemistry. 58. 4200-4201 (1993)

Satoshi Narizuka：“有机化合物的电解部分氟化。8.β-内酰胺的高度区域选择性阳极单氟化”有机化学杂志 58. 4200-4201 (1993)。

淵上 寿雄: "Selective Anodic Partial Fluorination of Heteroatom Compounds" Reviews on Heteroatom Chemistry. 10(印刷中). (1994)

Hisao Fuchigami：“杂原子化合物的选择性阳极部分氟化”杂原子化学评论 10（出版中）。

昆野 昭則: "Electrolytic Partial Fludination of Organic Compounds.VI.Highly Regioselective Electrochemical Monofluorination of Aliphitic Nitrogen-Containing Heterocycles" Tetrahedron Letters. 33. 7017-7020 (1992)

Akinori Konno：“有机化合物的电解部分氟化。VI.脂肪族含氮杂环的高度区域选择性电化学单氟化”四面体快报 33. 7017-7020 (1992)

T.Fuchigami, S.Narizuka, A.konno: "Ejectrolytic partial Fluorination of Organic Compouds. 4. Regioselective Anodic Monoflurination of 4-Thiazolidinonesand Its Application to the Synthesis of Monofluoo beta-Lactams" J.Org.Chem.57. 3755-3757 (1992)

T.Fuchigami、S.Narizuka、A.konno：“有机化合物的喷射部分氟化。4. 4-噻唑烷酮的区域选择性阳极单氟化及其在单氟 β-内酰胺合成中的应用”J.Org.Chem.57。

A.Konno, W.Naito, T.Fuchigami: "Eletrolytic Partial Fluorination of Organic Compounds. VI.Highly Regioselective Electrochemcal Monofluorination of Aliphatic Nitrogen-Containing Heterocycles." Tetrahedron Lett.33. 7017-7020 (1992)

A.Konno、W.Naito、T.Fuchigami：“有机化合物的电解部分氟化。VI.脂肪族含氮杂环的高度区域选择性电化学单氟化。”