フッ素薬学:官能基導入に力点を置いた創薬

2011 年度 研究成果報告書

• 研究課題/領域番号: 21390030
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 創薬化学
• 研究機関: 名古屋工業大学
• 研究代表者: 柴田 哲男 名古屋工業大学, 大学院・工学研究科, 教授 (40293302)
• 研究期間 (年度): 2009 – 2011
• キーワード: 医薬品化 / 有機化学 / フッ素 / 創薬 / 不斉合成 / 生理活性物質

研究概要

創薬開発に必要なトリフルオロメチル化,モノフルオロメチル化法の開発に成功した。いずれの場合も求電子的手法と求核的手法の2つの方法で検討した。特に求電子的手法については,取り扱いの容易な新しい試薬を開発することによって問題を克服した。求核的手法は触媒開発を基盤に展開した。また,生理活性発現機構をもとに新薬候補化合物の設計を行い,それらの合成に成功した。

研究成果

• [雑誌論文] Influence of New Fullerene Derivatives with Fluorocarbon Substituent on Performance of Polymer Solar Cells (2011)
  • 著者名/発表者名: Ichiko Yamada, Manoj Pandey, Yasuhiko Hayashi, Norio Shibata, Tesuo Saga, Takeshi Torub
  • 雑誌名: Physics Procedia 巻: 14 ページ: 192-197
  • 査読あり
• [雑誌論文] A New Synthetic Approach to Efavirenz through Enantioselective Trifluorome thylation by Using the Ruppert Prakash Reagent (2011)
  • 著者名/発表者名: Hiroyuki Kawai, Takashi Kitayama, Etsuko Tokunaga, Norio Shibata
  • 雑誌名: Eur. J. Org. Chem 巻: 30 ページ: 5959-5961
  • 査読あり
• [雑誌論文] Asymmetric Synthesis of Chiral Trifluoromethylated Heliotridane via Highly Catalytic Asymmetric Frieder-Crafts Alkylation with ls-Trifluorome thylated Acrylates and Pyrroles (2011)
  • 著者名/発表者名: Yiyong Hwang, Satoru Suzuki, Guokai Lin, Etsuko Tokunaga, Mo too Shire and Norio Shibata
  • 雑誌名: New. J. Chem 巻: 35 ページ: 2614-2621
  • 査読あり
• [雑誌論文] AsymmetricAllylic Monofluorome thylationand Methylation of Morita-Baylis-Hillman Carbonates with FBSM and BSM by Cooperative Cinchona Alkaloid/FeCl2 Catalysis (2011)
  • 著者名/発表者名: Tatsuya Furukawa, Jumper Kawazoe, wet Zhang, Takayuki Nishimine, Etsuko Tokunaga, Takashi Matsumoto, Dr. Mo too Shire, Prof. Norio Shibata
  • 雑誌名: Angew. Chem. Mt. Ed 巻: 50(41) ページ: 9684-9688
  • 査読あり
• [雑誌論文] Organocatalyzed Regia and Enantioselective Allylic Trifluoromethylation of Morita-Baylis Hillman Adducts Using Ruppert Prakash Reagent (2011)
  • 著者名/発表者名: Tatsuya Furukawa, Takayuki Nishimine, Etsuko Tokunaga, Kimiko Hasegawa, Mo too Shire, and Norio Shibata
  • 雑誌名: Org. Left 巻: 13(15) ページ: 3972-3975
  • 査読あり
• [雑誌論文] Construction of Trifluorome thyl Bearing Quaternary Carbon Centers by Intramolecular Decarboxylative Allylation of a Trifluoromethyl 6-Keto Esters (2011)
  • 著者名/発表者名: Norio Shibata, Satoru Suzukil, Tatsuya Furukawa, Hiroyuki Kawai, Etsuko Tokunaga, Zhe Yuan, Dominique Canard
  • 雑誌名: Adv. Synth. Catal 巻: 353(11-12) ページ: 2037-2041
  • 査読あり
• [雑誌論文] A Characterization of Maternal and Developmental Toxicity in Rabbits and Mice (2011)
  • 著者名/発表者名: Crystal J. J. Lee, Norio Shibata, Michael J. Wiley and Peter G. wellst
  • 雑誌名: Toxicol. Sci 巻: 122(1) ページ: 157-169
  • 査読あり
• [雑誌論文] Cu Mediated Chemo-selective Trifluoromethylation of Benzyl Bromides using Shelf-stable Electrophilic Trifluoromethylating Reagents (2011)
  • 著者名/発表者名: Hiroyuki Kawai, Tatsuya Furukawa, Yoshinori Nomura, Etsuko Tokunaga, and Norio Shibata
  • 雑誌名: Org. Left 巻: 13(14) ページ: 3596-3599
  • 査読あり
• [雑誌論文] Trifluoromethylation of Aromatic Isoxazoles : Regia and Di istereoselective Route to 5-Trifluoromethyl-2-isoxazolines (2011)
  • 著者名/発表者名: Hiroyuki Kawai, Kentaro Tachi, Etsuko Tokunaga, Dr. Motoo Shire, Prof. Norio Shibata
  • 雑誌名: Angew. Chem. Int. Ed 巻: 123(34) ページ: 7949-7952
  • 査読あり
• [雑誌論文] In vive Formation of a Glutathione Conjugate Derived from Thalidomide in Humanized uPA-NOG Mice (2011)
  • 著者名/発表者名: Hiroshi Yamazaki, Hiroshi Suemizu, She Igaya, Makiko Shimizu, Norio Shibata
  • 雑誌名: Chem. Res. Toxicol 巻: 24(3) ページ: 287-289
  • 査読あり
• [雑誌論文] Robust Synthesis of Trifluoromethionine and Its Derivatives by Reductive Trifluoromethylation of Amino Acid Disulfides by CFsI/NaILiq. NH3 system (2011)
  • 著者名/発表者名: Hiroyuki Yasui, Takeshi Yamamoto, Etsuko Tokunaga, Norio Shibata
  • 雑誌名: J Fluorine Chem 巻: 132(3) ページ: 186-189
  • 査読あり
• [雑誌論文] A sterically Demanding Electrophilic Fluorinating Reagent for Enantioselective Fluorination (2011)
  • 著者名/発表者名: Hiroyuki Yasui, Takeshi Yamamoto, Takehisa Ishimaru, Takeo Fukuzumi, Etsuko Tokunaga, Kakehi Akikazu, Mo too Shire, Norio Shibata
  • 雑誌名: J. Fluorine Chem 巻: 132(3) ページ: 222-225
  • 査読あり
• [雑誌論文] Catalyst-Free and Catalytic Friedel Crafts Alkylations of Indoles in Solkane(R) 365mfc, an Environmentally Benign Alternative Solvent (2011)
  • 著者名/発表者名: Xiu-Hua Xu, Akihiro Kusuda, Etsuko Tokunaga and Norio Shibata
  • 雑誌名: Green Chem 巻: 13 ページ: 46-50
  • 査読あり
• [雑誌論文] Organic Reaction in Solkane(R) 365mfc : Homocoupling Reaction of Terminal Alkynes (2011)
  • 著者名/発表者名: Akihiro Kusuda, Xiu-Hua Xu, Xin Wang, Etsuko Tokunaga and Norio Shibata
  • 雑誌名: Green Chem 巻: 13 ページ: 843-846
  • 査読あり
• [雑誌論文] Asymmetric Synthesis of Both Mirror Images of s' Fluorothalidomideby Enantiodivergent Fluorination Using a Single (2011)
  • 著者名/発表者名: Takeshi Yamamoto, Yuka Suzuki, Emi Ita, Etsuko Tokunaga, and Norio Shibata
  • 雑誌名: Org. Lef 巻: 13(3) ページ: 470-473
  • 査読あり
• [雑誌論文] Inherent Oxygen Preference in Enolate Monofluoromethylation and a Synthetic Entry to Monofluoromethyl Ethers (2011)
  • 著者名/発表者名: Yoshinori Nomura, Etsuko Tokunaga, Prof. Norio Shibata
  • 雑誌名: Angew. Chem. Int. Ed 巻: 50 ページ: 1885-1889
  • 査読あり
• [雑誌論文] A sterically Demanding Electrophilic Fluorinating Reagent for Enantioselective Fluorination (2011)
  • 著者名/発表者名: Hiroyuki Yasui, Takeshi Yamamoto, Takehisa Ishimaru, Takeo Fukuzumi, Etsuko Tokunaga, Kakehi Akikazu, Mo too Shire, Norio Shibata
  • 雑誌名: J. Fluorine Chem. 巻: 132(3) ページ: 222-225
  • 査読あり
• [雑誌論文] Robust Synthesis of Trifluoromethionine and Its Derivatives by Reductive Trifluoromethylation of Amino Acid Disulfides by CFsI/Na/Liq. NH3 system (2011)
  • 著者名/発表者名: Hiroyuki Yasui, Takeshi Yamamoto, Etsuko Tokunaga, Norio Shibata
  • 雑誌名: J. Fluorine Chem. 巻: 132(3) ページ: 186-189
  • 査読あり
• [雑誌論文] Catalyst-Free and Catalytic Frieder-Crafts Alkylations of Indoles in Solkane(R) 365mfc, an Environmentally Benign Alternative Solvent (2011)
  • 著者名/発表者名: Xiu-Hua Xu, Akihiro Kusuda, Etsuko Tokunaga, Norio Shibata
  • 雑誌名: Green Chem. 巻: 13 ページ: 46-50
  • 査読あり
• [雑誌論文] Inherent Oxygen Preference in Enolate Monofluorome thylation and a Synthetic Entry to Monofluoromethyl Ethers (2011)
  • 著者名/発表者名: Yoshinori Nomura, Etsuko Tokunaga, Norio Shibata
  • 雑誌名: Angew Chem. Int. Ed. 巻: 50 ページ: 1885-1889
  • 査読あり
• [雑誌論文] Asymmetric Synthesis of Both Mirror Images of s' Fluorothalidomide by Enantiodivergent Fluorination Using a Single (2010)
  • 著者名/発表者名: Takeshi Yamamoto, Yuka Suzuki, Emi Ita, Etsuko Tokunaga, Norio Shibata
  • 雑誌名: Org. Left. 巻: 12(22) ページ: 5104-5107
  • 査読あり
• [雑誌論文] Cinchona Alkaloid Catalyzed Asymmetric Trifluoromethylation of Alkynyl Ketones with Trimethylsilyl Trifluoromethane (2010)
  • 著者名/発表者名: Hiroyuki Kawai, Kentaro Tachi, Etsuko Tokunaga, Mo too Shire, Norio Shibata
  • 雑誌名: Org. Left. 巻: 12(22) ページ: 5104-5107
  • 査読あり
• [雑誌論文] Expeditious Synthesis of Trifluoromethylated Heterocycles : Noncatalytic 1, sDipolar Cyclization of Azomethine Imines with(aTrifluoromethyl) acrylates (2010)
  • 著者名/発表者名: Shinichi Ogawa, Takayuki Nishimine, Etsuko Tokunaga, Norio Shibata
  • 雑誌名: Synthesis 巻: 19 ページ: 3274-3281
  • 査読あり
• [雑誌論文] Enantioselective Syntehsis of Trifluoromethyl Substituted 2 Isoxazolines : Asymmetric Hydroxylamine/Enone Cascade Reaction (2010)
  • 著者名/発表者名: Kazutaka Matoba, Hiroyuki Kawai, Tatsuya Furukawa, Akihiro Kusuda, Etsuko Tokunaga, Shuichi Nakamura, Mo too Shire, Norio Shibata
  • 雑誌名: Angew. Chem. Int. Ed 巻: 49(33) ページ: 5762-5766
  • 査読あり
• [雑誌論文] Trifluoroethoxy Coating Improves the Axal Ligand Substitution of Subphthalocyanine (2010)
  • 著者名/発表者名: Norio Shibata, Banibrata Das, Etsuko Tokunaga, Mo too Shire, Nagao Kobayashi
  • 雑誌名: Chem. Eur : J 巻: 16(25) ページ: 7554-7562
  • 査読あり
• [雑誌論文] Chinchona alkaloid/Ti' vCatalyzed Enantioselective Enamine Trifluoropyruvate Condensation Cyclization Reaction anc Its Application to Drug-like Heterocycles (2010)
  • 著者名/発表者名: Shinichi Ogawa, Norihito Iida, Etsuko Tokunaga, Mo too Shire, Norio Shibata
  • 雑誌名: Chem. Eur J 巻: 16(24) ページ: 7090-7095
  • 査読あり
• [雑誌論文] Perfluoroisopropyl Zinc Phthalocyaines Conjugated with Deoxyribonucleosides : Synthesis, Photophysical Properties and In Vitro PHotodynamic Activities (2010)
  • 著者名/発表者名: Banibrata Das, Etsuko Tokunaga, Motohiro Tanaka, Takuma Sasaki, Norio Shibata
  • 雑誌名: Eur J. Org. Chem 巻: 15 ページ: 2878-2884
  • 査読あり
• [雑誌論文] Solubility of Trifluoroethoxyphthalocyanines and Subphthalocyanines in Liquid and Supercritical Carbon Dioxide (2010)
  • 著者名/発表者名: Banibrata Das, Etsuko Tokunaga, Norio Shibata, Nagao Kobayashi
  • 雑誌名: J. Fluorine Chem 巻: 131(5) ページ: 652-654
  • 査読あり
• [雑誌論文] Enantioselective Frieder-Crafts Reaction of lsTrifluoromethylated Acrylates with Pyrroles and Its Application to the Synthesis of Trifluorinated Heliotridane (2010)
  • 著者名/発表者名: Yiyong Hwang, Etsuko Tokunaga, Satoru Suzuki, Mo too Shire, Norio Shibata
  • 雑誌名: Org. Left 巻: 12(5) ページ: 1136-1138
  • 査読あり
• [雑誌論文] Synthesis of Benzenecentered Trinuclear Phthalocyanines by Triple-click Chemistry (2010)
  • 著者名/発表者名: Banibrata Das, Masashi Umeda, Etsuko Tokunaga, Takeshi Torn, Norio Shibata
  • 雑誌名: Chem. Left 巻: 39(4) ページ: 337-338
  • 査読あり
• [雑誌論文] Self Disproportionation of Enantiomers of Heterocyclic Compounds Having a Tertiary Trifluoromethyl Alcohol Center on Chromatography with a Non Chiral System (2010)
  • 著者名/発表者名: Shinichi Ogawa, Takayuki Nishimine, Etsuko Tokunaga, Shuichi Nakamura Norio Shibata
  • 雑誌名: J Fluorine Chem 巻: 131(4) ページ: 521-524
  • 査読あり
• [雑誌論文] 2-Fluoro-1, 3-benzodithiole-1, 1, 3, 3-tetraoxide : A Reagent for Nucleophilic Monofluoromethylation of Aldehydes (2010)
  • 著者名/発表者名: Tatsuya Furukawa, Yosuke Goto, Jumper Kawazoe, Etsuko Tokunaga, Shuichi Nakamura, Yudong Yang, Hongguang Du, Akikazu Kakehi, Mo too Shire, Norio Shibata
  • 雑誌名: Angew. Chem. Mt. Ed 巻: 49(9) ページ: 1642-1647
  • 査読あり
• [雑誌論文] Efficient Access to Extended Yagupolskii Umemoto-Type Reagents : Triflic Acid Catalyzed Intramolecular Cyclization of or the Ethynylaryltrifluoromethylsulfanes (2010)
  • 著者名/発表者名: Andrej Matsnev, Shun Noritake, Yoshinori Nomura, Etsuko Tokunaga, Shuichi Nakamura, Norio Shibata
  • 雑誌名: Angew. Chem. Mt. Ed 巻: 49(3) ページ: 572-576
  • 査読あり
• [雑誌論文] Synthesis of Fluorinated Alienes via Palladium Catalyzed Monofluoromethylation Using FBSM (2009)
  • 著者名/発表者名: Masamichi Ogasawara, HidetoshiMurakami, Tatsuya Furukawa, Tamotsu Takahashi, Norio Shibata
  • 雑誌名: Chem. Commun 巻: 47 ページ: 7366-7368
  • 査読あり
• [雑誌論文] Construction of Nonadjacent Stereocenters Containing a Trifluoromethylated Carbon by Organocatalyzed Michael Addition of lsKetoesters to 2(Trifluoromethyl) acrylate (2009)
  • 著者名/発表者名: Shinichi Ogawa, Hiroyuki Yasui, Shuichi Nakamura, Norio Shibata
  • 雑誌名: Chem. Left 巻: 10 ページ: 1006-1007
  • 査読あり
• [雑誌論文] Design and Synthesis of Thalidomide Deoxyribonucleoside Chimeras (2009)
  • 著者名/発表者名: Shigeru Suzuki, Takeshi Yamamoto, Etsuko Tokunata, Shuichi Nakamura, Motohiro Tanaka, Takuma Sasaki, Norio Shibata
  • 雑誌名: Chem. Lef 巻: 11 ページ: 1046-1047
  • 査読あり
• [雑誌論文] Asymmetric Synthesis of a Sulfenyl(sketoesters Using DBFOXPh/Ni(II) complex (2009)
  • 著者名/発表者名: Takehisa Ishimaru, Shinichi Ogawa, Etsuko Tokunaga, Shuichi Nakamura, Norio Shibata
  • 雑誌名: J. Fluorine Chem 巻: 130(11) ページ: 1049-1053
  • 査読あり
• [雑誌論文] Solkane(R) 365mfc is an Environmentally Benign Alternative Solvent for Trifluoromethylation Reaction (2009)
  • 著者名/発表者名: Akihiro Kusuda, Hiroyuki Kawai, Shuichi Nakamura, Norio Shibata
  • 雑誌名: Green Chem 巻: 11 ページ: 1733-1735
  • 査読あり
• [雑誌論文] Catalytic Enantioselective Trifluoro methylation of Azomethine Imines With Trimethyl(trifluoromethyl) (2009)
  • 著者名/発表者名: Hiroyuki Kawai, Akihiro Kusuda, Shuichi Nakamura, Mo too Shire, Norio Shibata
  • 雑誌名: Angew. Chem. Mt. Ed 巻: 48(34) ページ: 6324-6327
  • 査読あり
• [雑誌論文] Photophysical and Electrochemical Properties of Perfluoroisopropyl Substituted Binuclear Phthalocyanine Conjugated with a Butadiyne Linker (2009)
  • 著者名/発表者名: Norio Shibata, Banibrata Das, Masamichi Hayashi, Shuichi Nakamura, Takeshi Torn
  • 雑誌名: J. Fluorine Chem 巻: 130(12) ページ: 1164-1170
  • 査読あり
• [雑誌論文] A DBFOXPh-Based Combinatorial Catalyst for Enantioselective Fluorination of Aryl Acetyl and sButenoyl Thiazolidinones (2009)
  • 著者名/発表者名: hande Sudhakar Reddy, Norio Shibata, Takao Horikawa, Satoru Suzuki, Shuichi Nakamura, Takeshi Torn, Mo too Shire
  • 雑誌名: Chemistry An Asian Journal 巻: 4(9) ページ: 1411-1415
  • 査読あり
• [雑誌論文] Synthesis of Novel C2Symmetric Chiral Crown Ethers and Their Applications to Enantioselective Trifluoromethylation of Aldehydes and Ketones (2009)
  • 著者名/発表者名: Hiroyuki Kawai, Akihiro Kusuda, ShuichiNakamura, Satoshi Mizuta, Yasuhiro Funahashi, Hideki Masuda, Norio Shibata
  • 雑誌名: J. Fluorine Chem 巻: 130(8) ページ: 762-765
  • 査読あり
• [雑誌論文] Enantioselective Electrophilic Trifluoro methylation of ls-Keto Esters with Umemoto Reagents Induced by Chiral Nonracemic Guanidine (2009)
  • 著者名/発表者名: Shun Noritake, Norio Shibata, Yoshinori Nomura, Yiyong Hwang, Andrej Matsnev, Shuichi Nakamura, Takeshi Toni, Dominique Canard
  • 雑誌名: Org. Biomol. Chem 巻: 7 ページ: 3599-3604
  • 査読あり
• [雑誌論文] Ionic Liquids as Media for Nucleophilic Ring Opening Fluorination of Aziridines (2009)
  • 著者名/発表者名: Shun Noritake, Norio Shibata, Hiroyuki Kawai, Pandy Manoj Kumar, Shuichi Nakamura, Takeshi Torn
  • 雑誌名: Heterocycl. Commun 巻: 15(2) ページ: 105-113
  • 査読あり
• [雑誌論文] Synthesis of Trifluoroethoxy Coated Binuclear Phthalocyanines with Click Spacers and Investigation of Their Clamshell (2009)
  • 著者名/発表者名: Behaviour, Yoshiyama, Norio Shibata, Takefumi Sate, Shuichi Nakamura, Takeshi Toru
  • 雑誌名: Org. Biomol. Chem 巻: 7(11) ページ: 2265-2269
  • 査読あり
• [学会発表] Asymmetric Allylic Fluoroalkylation of Morita BaylisHillman Adducts Catalyzed by Cinchona Alkaloid (2011)
  • 著者名/発表者名: Takayuki Nishimine, Tatsuya Furukawa, Jumper Kawazoe, Wet Zhang, Etsuko Tokunaga, Norio Shibata
  • 学会等名: International Symposium on Catalysis and Fine Chemicals
  • 発表場所: Nara, Japan
  • 年月日: 20111204-08
• [学会発表] Palladiumcatalyzed Decarboxylative Allylation of uTrifluoromethyl R-Keto Esters (2011)
  • 著者名/発表者名: Satoru Suzuki, Etsuko Tokunaga, Norio Shibata
  • 学会等名: International Symposium on Catalysis and Fine Chemicals
  • 発表場所: Nara, Japan
  • 年月日: 20111204-08