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.

直接氟化法和分子转化法开发具有生物活性的氟化合物在安全性、选择性和效率方面存在许多问题。从这一点出发，我们开发了一种非常有效的方法，通过阳极氟化来制备含氟的β-内酰胺类药物。4-噻唑烷酮类化合物的高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我们成功地实现了4-噻唑烷酮类化合物(1)在氟离子存在下的阳极氧化反应，实现了高效、高选择性的单氟化反应。这是第一个成功的含硫杂环阳极氟化反应的例子。研究发现，含氟1，2，4，6，6，6，6，6，6，6，6，5，6，6-三氟乙内酰胺类化合物的热分解反应得到了单氟β-内酰胺类化合物。选择性阳极单氟化β-内酰胺类抗生素：我们首次成功地进行了β-内酰胺类抗生素的部分氟化反应。研究发现，α-苯基亚硫基-β-内酰胺类化合物具有很高的区域选择性和较高的电流效率，并且具有很高的产率。结果表明，这种新的阳极氧化方法优于传统的化学方法。因此，我们几乎完成了我们计划的项目。

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。”