Drug Design of Fluorinated Quinolone Carboxylic Acid Related Compounds and the Test of Biological Activities.

氟化喹诺酮羧酸相关化合物的药物设计及生物活性测试。

• 批准号: 04555204
• 负责人: UNEYAMA Kenji
• 金额: $ 7.04万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04555204/
• 关键词: Fluoro-compound; Fluorination; Electrolysis; スピロジアザカルボサイクル; トリフルオロメチルベンゾイミダゾール; いもち病; キノロンカルボン酸; フッ素化; フッ素化合物; トリフルオロメチル; トリフルオロアセトイミドイル

Trifluoroacetimidoyl metals (Li, Zn, Pd, Si) and telluride (1) have been prepared as precursors for the trifluoroacetimidoyl carbanion and the corresponding radicals and have been employed for the syntheses of fluorinated nitrogen heterocycles. Photolysis of the telluride and the iodide leads to homolytic cleavage of the C-Te and C-I bonds to generate the desired trifluoroacetimidoyl radical which undergoes intramolecular cyclization. The reaction provided 3-oxy-2-trifluoromethyl indols (3) , (5) . Meanwhile, palladium catalyzed carboalkoxylation of the trifluoroacetimidoyl iodides and subsequent alkylation and hydrogenation provided various kinds of fluorinated alpha-aminoacids. Optical active trifluoroalanine (2) was synthesized. Lithium-iodine exhange reaction of the iodides generated the acetimidoyl lithium which is stable below -65ﾟC and alkylated. By these newly developed methods, some interesting heterocycles (3) - (6) have been synthesized.

三氟亚氨基金属（Li、Zn、Pd、Si）和碲化物（1）已被制备为三氟亚氨基碳负离子和相应自由基的前体，并已用于合成氟化氮杂环。碲化物和碘化物的光解导致C-Te和C-I键均裂，产生所需的三氟乙酰亚氨基自由基，该自由基经历分子内环化。该反应提供3-氧基-2-三氟甲基吲哚(3)、(5)。同时，钯催化三氟亚氨基碘化物的烷氧基化以及随后的烷基化和氢化，得到各种氟化α-氨基酸。合成了光学活性三氟丙氨酸(2)。碘化物的锂-碘交换反应生成乙酰亚氨基锂，其在-65℃以下稳定并烷基化。通过这些新开发的方法，合成了一些有趣的杂环(3) - (6)。

项目成果

K. Tamura, Fengyang Yan, T. Sakai, K. Uneyama: "Generation and Reaction of N-Aryltrifluoroacettmidoyl Zinc" Bull. Chem.Soc. Jpn.67. 300-303 (1994)

K. Tamura、Fengyang Yan、T. Sakai、K. Uneyama：“N-芳基三氟乙酰氨基锌的生成和反应”公报。

K.Uneyama,K.Sugimoto: "N-Substituted 2,2,2-Trifluoroethanimidic Acid 1-Methyl-ethylidene Hydrazides as Synthetic Blocks for Trifluoro-methylated Nitrogen Heterocycles" J.Org.Chem.,. 57. 6015-6019 (1992)

K.Uneyama,K.Sugimoto：“N-取代的 2,2,2-三氟乙亚胺酸 1-甲基亚乙基酰肼作为三氟甲基化氮杂环的合成嵌段”J.Org.Chem.,。

M. Kobayashi, K. Uneyama, N. Hamada, S. Kashino: "Thermal Electrocyclic Spirocyclization of p-Benzo-quinone Imines" Tetrahedron Letters. 35. 5235-5238 (1994)

M. Kobayashi、K. Uneyama、N. Hamada、S. Kashino：“对苯并醌亚胺的热电环螺环化”四面体快报。

H.Watanabe,F-Y Yan,T.Sakai,K.Uneyama: "(Trifluoroacetimidaye)lithiums and Their Reaction with Electrophiles" J.Org、Chem.59. 758-761 (1994)

H.Watanabe、F-Y Yan、T.Sakai、K.Uneyama：“（三氟乙酰亚胺）锂及其与亲电试剂的反应”J.Org，Chem.59（1994）。

Kenji Uneyama: "One-pot Synthesis of Trifluoroacetimidoyl Halides" J.Org.Chem.58. 32-35 (1993)

Kenji Uneyama：“三氟乙酰亚氨基卤化物的一锅合成”J.Org.Chem.58。