2001 Fiscal Year Annual Research Report

環境調和型反応に重点を置いた生物活性天然物の大量合成手法の開発と創薬研究

Research Project

Project/Area Number	13853010
Research Institution	Osaka University
Principal Investigator	北泰行大阪大学, 薬学研究科, 教授 (00028862)
Co-Investigator(Kenkyū-buntansha)	当麻博文大阪大学, 薬学研究科, 助手 (50271028) 赤井周司大阪大学, 薬学研究科, 助手 (60192457) 藤岡弘道大阪大学, 薬学研究科, 助教授 (10173410)
Keywords	グリーンケミストリー / ポリマー担時型超原子価ヨウ素試薬 / 水中での酸化反応 / 酸化的ビアリールカップリング反応 / エトキシビニルエステル / リパーゼ触媒不斉エステル交換反応 / ドミノ型不斉反応 / ラジカル環化
Research Abstract	環境調和型反応に重点を置きながら、生物活性天然物を大量供給するための基盤反応の開発研究を行なった。 1.リサイクル可能な反応剤であるポリマー担持型超原子価ヨウ素試薬を水中で用いて、各種アルコール類からカルボン酸類、ケトン類、及びラクトン類への簡便かつ効果的な酸化反応、並びにp-ジメトキシベンゼン類の酸化的脱メチル化反応を経るp-キノン類の収率の良い合成反応を開発した。更にリサイクル型超原子価ヨウ素試薬を有機溶媒中で用いることにより、効果的なビアリール化合物合成に成功し、また、この反応にリサイクル可能な固体酸触媒であるヘテロポリ酸を添加すると、反応収率が向上すると共に、後処理を簡便化出来た。 2.エトキシビニルエステルを用いるリパーゼ触媒不斉エステル交換反応で、従来の酵素反応では困難であった対称性1,3-ジオール類の高効率的な不斉非対称化法を開発し、不斉四級炭素の短工程構築に成功した。更に、構造修飾したエトキシビニルエステルを用いて、3-ブロモフルフリルアルコール類のリパーゼ触媒光学分割と、分子内Diels-Alder反応が連続するドミノ型不斉反応を開発し、有用なキラルシントンとなる7-オキサビシクロヘプテン類を1段階で不斉合成できる、安全かつ廃棄物の少ない優れた合成法を確立した。 3.水溶性ラジカル開始剤と界面活性剤との組み合わせによって、脂溶性有機化合物を水中でラジカル環化させることに初めて成功した。またキノン-O, S-アセタールを用いるスルフェニル化反応、ポリマー担持型トリフェニルホスフィンを用いる各種アルコール類からヨウ素化物への簡便な変換法、CH-π相互作用を利用する絶対配置決定法や光学分割法など、中性に近い緩和な条件下での高効率的な反応を開発した。

Research Products

(19 results)

All Other

All Publications (19 results)

[Publications] TOHMA, Hirofumi: "Efficient Oxidative Biaryl Coupling Reaction of Phenol Ether Derivatives Using Hypervalent Iodine(III) Reagents"Tetrahedron. 57. 345-352 (2001)
[Publications] ARISAWA, Mitsuhiro: "Hypervalent Iodine(III)-Induced Intramolecular Cylization of α-(Aryl)alkyl-β-dicarbonyl Compounds : A Convenient Synthesis of Benzannulated and Spirobenzannulated Compounds"Jounal of Organic Chemistry. 66. 59-65 (2001)
[Publications] TOHMA, Hirofumi: "Novel and Efficient Synthesis of p-Quinones in Water via Oxidative Demethylation of Phenol Ethers Using Hypervalent Iodine(III) Reagents"Tetrahedron Letters. 42. 6899-6902 (2001)
[Publications] AKAI, Shuji: "Lipase-Catalyzed Enantioselective Desymmetrixztion of Prochiral 3, 3-Bis(hydroxymethyl)oxindoles"Tetrahedron Letters. 42. 7315-7317 (2001)
[Publications] AKAI, Shuji: "Enantiodivergent Synthesis of Either Enantiomer of ABCDE-Ring Analog of Antitumor Antibiotic, Fredericamycin A via Intramolecular [4+2] Cycloaddition Approach"Organic Letters. 3. 4015-4018 (2001)
[Publications] MATSUGI, Masato: "Regioselective Nucleophilic Addition of Methoxybenzene Derivatives to the β-Carbon of p-Benzoquinone Mono O, S-Acetal"Chem. Pham. Bull.. 49. 1658-1659 (2001)
[Publications] MATSUGI, Masato: "Facile and Efficient Sulfenylation Method Using Quinone Mono-O, S-Acetals unde Mild Conditions"Journal of Organic Chemistry. 66. 2434-2441 (2001)
[Publications] MATSUGI, Masato: "An Efficient Sulfenylation of Aromatics Using Highly Active Quinone Mono-O, S-Acetal Bearing a Pentafluorophenylthio Group"Tetrahedron Letters. 42. 1077-1080 (2001)
[Publications] KITA, Yasuyuki: "A Novel and Efficient Methodology for the C-C Bond Forming Radical Cyclization of Hydrophobic Substartes in Water"Organic Letters. 3. 1157-1160 (2001)
[Publications] MATSUGI, Masato: "Determination of Absolute Configuration of trans-2-Arylcyclohexanols Using Remarkable Aryl-Induced 'H NMR Shifts in Diastereomeric Derivatives"Tetrahedron Letters. 42. 6903-6905 (2001)
[Publications] MATSUGI, Masato: "Determination of Stereochemistry and Separation of Distereomeric Derivatives of trans-2-Pyridylcyclohexanols by Extraction"Tetrahedron Letters. 42. 8039-8072 (2001)
[Publications] MATSUGI, Masato: "A Novel Determination Method of the Absolute Configuration of 1-Aryl-1-Alkyl alcohols and Amines by an Intramolecular CH/π Shielding Effect in 'H NMR"Tetrahedron Letters. 42. 8019-8022 (2001)
[Publications] 赤井, 周司: "リパーゼの不斉識別能を活用する新規不斉合成反応の開発研究"生産技術誌. 53. 57-60 (2002)
[Publications] AKAI, Ahuji: "An Efficient Lipase-Catalyzed Enantioselective Desymmetrization of Prochiral 2,2-Disubstituted 1,3-Propanediols and Meso 1,2-Diols Using 1-Ethoxyvinyl 2-Furoate"Journal Organic Chemistry. 67. 411-419 (2002)
[Publications] HAMAMOTO, Hiromi: "A Novel and Efficient Oxidative Biaryl Coupling Reaction of Phenol Ether Derivatives Using a Combination of Hypervalent Iodine(III) Reagent and Heteropoly Acid"Chemical Communication. 450-451 (2002)
[Publications] TOHMA, Hirofumi: "Synthetic Studies on Sulfur Cross-linked Core of Antitumor Marine Alkaloid, Discorhabdins : Total Synthesis of Discorhabdin A"Angew. Chem. Int. Ed.. 41. 348-350 (2002)
[Publications] ANILKUMAR, Gopinathan: "A Simple and Efficient Iodination of Alochols on Polymer Supported Triphenylphoshine"Journal of Chemical Society, Perkin Trconsaction 1. (印刷中). (2002)
[Publications] TOHMA, Hirofumi: "Facile and Clean Oxidation of Alcohols in Water Using Hypervalent Iodine(III)Reaents"Adv. Synth. Catal.. (印刷中). (2002)
[Publications] KITA, Yasuyuki: "Radicals in Organic Synthesis : Volume 1 : Basic Principles"Renaud, P., Sibi, M.P., ed.(Wiley-VCH). 10 (2001)

2001 Fiscal Year Annual Research Report

環境調和型反応に重点を置いた生物活性天然物の大量合成手法の開発と創薬研究

Principal Investigator

北 泰行 大阪大学, 薬学研究科, 教授 (00028862)

Research Products

[Publications] TOHMA, Hirofumi: "Efficient Oxidative Biaryl Coupling Reaction of Phenol Ether Derivatives Using Hypervalent Iodine(III) Reagents"Tetrahedron. 57. 345-352 (2001)

[Publications] ARISAWA, Mitsuhiro: "Hypervalent Iodine(III)-Induced Intramolecular Cylization of α-(Aryl)alkyl-β-dicarbonyl Compounds : A Convenient Synthesis of Benzannulated and Spirobenzannulated Compounds"Jounal of Organic Chemistry. 66. 59-65 (2001)

[Publications] TOHMA, Hirofumi: "Novel and Efficient Synthesis of p-Quinones in Water via Oxidative Demethylation of Phenol Ethers Using Hypervalent Iodine(III) Reagents"Tetrahedron Letters. 42. 6899-6902 (2001)

[Publications] AKAI, Shuji: "Lipase-Catalyzed Enantioselective Desymmetrixztion of Prochiral 3, 3-Bis(hydroxymethyl)oxindoles"Tetrahedron Letters. 42. 7315-7317 (2001)

[Publications] AKAI, Shuji: "Enantiodivergent Synthesis of Either Enantiomer of ABCDE-Ring Analog of Antitumor Antibiotic, Fredericamycin A via Intramolecular [4+2] Cycloaddition Approach"Organic Letters. 3. 4015-4018 (2001)

[Publications] MATSUGI, Masato: "Regioselective Nucleophilic Addition of Methoxybenzene Derivatives to the β-Carbon of p-Benzoquinone Mono O, S-Acetal"Chem. Pham. Bull.. 49. 1658-1659 (2001)

[Publications] MATSUGI, Masato: "Facile and Efficient Sulfenylation Method Using Quinone Mono-O, S-Acetals unde Mild Conditions"Journal of Organic Chemistry. 66. 2434-2441 (2001)

[Publications] MATSUGI, Masato: "An Efficient Sulfenylation of Aromatics Using Highly Active Quinone Mono-O, S-Acetal Bearing a Pentafluorophenylthio Group"Tetrahedron Letters. 42. 1077-1080 (2001)

[Publications] KITA, Yasuyuki: "A Novel and Efficient Methodology for the C-C Bond Forming Radical Cyclization of Hydrophobic Substartes in Water"Organic Letters. 3. 1157-1160 (2001)

[Publications] MATSUGI, Masato: "Determination of Absolute Configuration of trans-2-Arylcyclohexanols Using Remarkable Aryl-Induced 'H NMR Shifts in Diastereomeric Derivatives"Tetrahedron Letters. 42. 6903-6905 (2001)

[Publications] MATSUGI, Masato: "Determination of Stereochemistry and Separation of Distereomeric Derivatives of trans-2-Pyridylcyclohexanols by Extraction"Tetrahedron Letters. 42. 8039-8072 (2001)

[Publications] MATSUGI, Masato: "A Novel Determination Method of the Absolute Configuration of 1-Aryl-1-Alkyl alcohols and Amines by an Intramolecular CH/π Shielding Effect in 'H NMR"Tetrahedron Letters. 42. 8019-8022 (2001)

[Publications] 赤井, 周司: "リパーゼの不斉識別能を活用する新規不斉合成反応の開発研究"生産技術誌. 53. 57-60 (2002)

[Publications] AKAI, Ahuji: "An Efficient Lipase-Catalyzed Enantioselective Desymmetrization of Prochiral 2,2-Disubstituted 1,3-Propanediols and Meso 1,2-Diols Using 1-Ethoxyvinyl 2-Furoate"Journal Organic Chemistry. 67. 411-419 (2002)

[Publications] HAMAMOTO, Hiromi: "A Novel and Efficient Oxidative Biaryl Coupling Reaction of Phenol Ether Derivatives Using a Combination of Hypervalent Iodine(III) Reagent and Heteropoly Acid"Chemical Communication. 450-451 (2002)

[Publications] TOHMA, Hirofumi: "Synthetic Studies on Sulfur Cross-linked Core of Antitumor Marine Alkaloid, Discorhabdins : Total Synthesis of Discorhabdin A"Angew. Chem. Int. Ed.. 41. 348-350 (2002)

[Publications] ANILKUMAR, Gopinathan: "A Simple and Efficient Iodination of Alochols on Polymer Supported Triphenylphoshine"Journal of Chemical Society, Perkin Trconsaction 1. (印刷中). (2002)

[Publications] TOHMA, Hirofumi: "Facile and Clean Oxidation of Alcohols in Water Using Hypervalent Iodine(III)Reaents"Adv. Synth. Catal.. (印刷中). (2002)

[Publications] KITA, Yasuyuki: "Radicals in Organic Synthesis : Volume 1 : Basic Principles"Renaud, P., Sibi, M.P., ed.(Wiley-VCH). 10 (2001)

北泰行大阪大学, 薬学研究科, 教授 (00028862)