1997 Fiscal Year Annual Research Report

特異構造合成ブロックの開発と生理活性分子設計への応用

Research Project

Project/Area Number	07555285
Research Institution	NAGOYA UNIVERSITY,GRADUATE SCHOOL OF ENGINEERING
Principal Investigator	江口昇次名古屋大学, 工学研究科, 教授 (50023099)
Co-Investigator(Kenkyū-buntansha)	岡野孝名古屋大学, 工学研究科, 助手 (90194373) 大野正富名古屋大学, 工学研究科, 助教授 (50072682)
Keywords	イミノホスホラン / プテリジン / アルキニルシラン / [60]フラーレン / ニトロン / スクアリン酸 / 不斉合成 / トリフルオロメチル化合物
Research Abstract	本研究では特異構造化合物の反応性を解明し合成的変換法を確立していくとともに生理活性分子設計に応用することによってユニークな新規合成ブロックとしての開発と実用化の研究を押し進めることを目的としている。本年度の研究実施計画に沿って検討した結果以下に要約できる成果を得た。 (1)多環系骨格誘導体合成法の開拓と生物活性の探索:設計イミノホスホランの2種類のカルボニル基への分子内aza-Wittig反応性を検討し6員環キナゾリノンと7員環ジアゼピノンのケモ選択性を解明し、新たに光学活性Benzomalvin AおよびBの合成法を開発した。また前者のユニークなコンフォメーション変化の解明にも成功した。分子間aza-Wittig反応/へテロ環化法によるプテリジン、デアザプテリジンの新規合成法を開発した.またニトロン環化付加-転位反応によりピロロジヒドロイソキノリン合成法を開発した。 (2)C60フラーレンの付加反応性の解明とそれらのヘテロ環誘導体合成法の開発および諸性質の解明:ヘテロDiels-Alder反応や複素環のo-キノジメタン型ジエンの[2+4]環化付加反応、ニトロ化合物から容易にできるるシロキシニトロン[2+3]環化付加反応がC60と円滑に進行し、複素環縮合または連結型C60誘導体の合成ルートを開発した。これらのヘテロ環部変環反応法を開発した。 (3)スクアリン酸誘導体の環変換反応による骨格合成法の開発と生理活性分子合成への応用:研究代表者らの見出したスクアリン酸アセタール誘導体への不飽和シラン類の付加反応においてアルキニルシラン類の親電子付加反応では興味ある1,2-Si転位、開環,5-exo-trig環化の新機構によるシクロペンテンジオン合成法を見出した。 (4)入手容易なパ-フルオロアルキル誘導体を活用した新規含フッ素合成中間体の開発とその生理活性分子設計への応用:容易に安価で入手できるトリフルオロ酢酸エステルを出発原料としてラジカル環化反応等により橋頭位トリフルオロメチル化5〜6員環含窒素複素環の合成ルートを開発した。またキラルトリフルオロフェニルスルフォニルプロペン誘導体合成とその[3+2]および[4+2]環化付加反応、Michael付加反応により光学活性トリフルオロメチル化合物合成法を開発した。

Research Products
(20 results)

All Other

All Publications (20 results)

[Publications] Takashi Okano: "Synthesis of Indolizidine Derivatives Trifluoromethylated at Bridgehead Position via Acyliminium Intermediate Derived From Ring-Chain Tautomerism of 5,5,5-Trifluoro-4-oxopentanoyl Arylethylamide" Heterocycles. 44(1). 227-236 (1997)
[Publications] Hiroyasu Tsuge: "Synthesis of 1-(3,3,3-Trifluoro-1-propenylsulfonyl)pyrrolidine and Its Michael Addition with Some Selected Nucleophiles" Heterocyclic Commun. 3(1). 19-22 (1997)
[Publications] He--ping Zeng: "Selective Formation of Mono- and Tetra-Cycloadducts by the Diels-Alder Reaction of[60]fullerene with 2,5-Dimethylthiophene S-Oxides" Synlett. (2). 175-176 (1997)
[Publications] Hiroyasu Tsuge: "Highly Diasteroselective Michael Addition to Optically Active Trifluoromethylated α、β-Unsaturated Sulfonamides Based on Their Hinge-Like Conformation" Tetrahedron. 53(3). 823-838 (1997)
[Publications] Yoshihiko Yamamoto: "Formation of 2-[1-(Trimethylsilyl)alkylidene]-4-cyclopentene-1,3-dione from Lewis Acid-Catalyzed Reaction of Cyclobutenedione Monoacetal with Alkynylsilane:Novel Cationic 1,2-Silyl Migrative Ring Opening and Subsquent 5-Exo-Trig Ring Closure" J.Org.Chem.62(5). 1292-1298 (1997)
[Publications] Bao-Xiang Zhau: "Synthesis of Nitrones from 3,4-Dihydroisoquinoline Derivatives by Oxidation with m-Chloropeoxybenzoic Acid" Org.Prep.& Proced.Int.29(2). 185-194 (1997)
[Publications] Yang Yu: "Synthesis of 2-Aza-3-oxatetracyclo[7.3.1.17,11.02,6]tetradecane Derivatives by the 1,3-Dipolar Cycloaddition Reaction of Homoadamantane-Incorporated Nitrones with Alkenes" Tetrahedron. 53(15). 5413-5422 (1997)
[Publications] Hiroyasu Tsuge: "Asymmetric 1,3-Dipolar Cycloaddition of Optically Active Trifluoromethylated α,β-Unsaturated Aryl Sulfones with Nitrones:the Use of o-Dialkylaminoethyl Chiral Auxiliaries" J.Chem.Soc.,Perkin Trans 1. (10). 1581-1586 (1997)
[Publications] Masatomi Ohno: "Synthesis of Heterocycle-Linked[60]Fullerene Derivatives by Heterocyclic o-Quinodimethane Diels-Alder Reaction and Self-Sensitized Photooxygenation of the Cycloadducts" Tetrahedron. 53(27). 9075-9086 (1997)
[Publications] Bao-Xiang Zhau: "1,3-Dipolar Cycloaddition Reaction of Substituted 3,4-Dihydroisoquinoline N-Oxides with Allenes" Tetrahedron. 53(28). 9575-9584 (1997)
[Publications] Toshiyuki Sugimori: "The First Total Synthesis of(-)-Benzomalvin A via Intramolecular Aza-Wittig Reaction" Chem.Lett.(9). 869-891 (1997)
[Publications] Masatomi Ohno: "スクアリン酸を合成素子とする多官能型炭素及び複素環化合物の高選択的合成" 有機合成化学協会誌. 55(9). 785-792 (1997)
[Publications] Takashi Okano: "Cyclization of Hindered Fluorinated Dichloro(5- and 6-)alkenyl Radicals.Structural Effects of Olefins on the Selective Formation of 5-exo and 6-endo Cyclization Products" J.Org.Chem.62(21). 7192-7200 (1997)
[Publications] Tomohiro Okwa: "One-pot Synthesis of Novel(2-Oxo-1,2-dihydropyridin-3-yl)-1,3,5-triazine Derivatives from Methyl 2-(N-Triphenylphosphoranlidene)aminonicotinate,Arylisocyanates and Primary Amines" Tetrahedron. 53(47). 16061-16082 (19997)
[Publications] Bao-Xiang Zhau: "Synthesis of 5,6-Dihydropyrrolo[2.1-α]isoquinolines by Rearrangement of 5-Methyleneisoxazolidines Generated from 1,3-Dipolar Cycloaddition of 3,4-Dihydroisoquinoline N-Oxides with Allenes:A Novel Consecutive Rearrangement to Fused-Ring Pyrrole Derivatives" J.Chem.Soc.,Perkin Trans 1. (21). 2973-2977 (1997)
[Publications] Masatomi Ohno: "Fusion of C60 with Cyclic Amino Acid and Thiourea by Hetero Diels-Alder Reactions" Heterocycles. 46(1). 49-52 (1997)
[Publications] Shoji Eguchi: "Synthesis of Heterocycle-Containing[60]Fulleren Derivatives.II.Recent Progress in [4+2]-and[3+2]-Cycloaddition Routes,Eguchi" Fullerene Sci.& Tech.5(5). 977-987 (1997)
[Publications] Tomohiro Okwa: "Chemoselectivity in the Intramolecular Aza-ittig Reaction of N-[2-(Trisubstituted Phosphoranilylidene)aminobenzoyl]-2-pyridone-5-carboxylic Acid Derivatives." Heterocycles. 47(1). 375-382 (1998)
[Publications] Shoji Eguchi(分担執筆): "Synthesis of Heterocyclic Natural Products and Related Heterocycles by the Aza-Wittig Methodology in "Recent Research Developement in Organic Chemistry"" Transworld Research Network, 12/000 (1998)
[Publications] Shoji Eguchi(分担執筆): "Molecular Design of Novel Carbo- & Heteropolycycles based on Adamantane in "Recent Research Developement in Pure and Applied Chemistry"" Transworld Research Network, 12/000 (1998)

1997 Fiscal Year Annual Research Report

特異構造合成ブロックの開発と生理活性分子設計への応用

Principal Investigator

江口 昇次 名古屋大学, 工学研究科, 教授 (50023099)

Research Products

[Publications] Takashi Okano: "Synthesis of Indolizidine Derivatives Trifluoromethylated at Bridgehead Position via Acyliminium Intermediate Derived From Ring-Chain Tautomerism of 5,5,5-Trifluoro-4-oxopentanoyl Arylethylamide" Heterocycles. 44(1). 227-236 (1997)

[Publications] Hiroyasu Tsuge: "Synthesis of 1-(3,3,3-Trifluoro-1-propenylsulfonyl)pyrrolidine and Its Michael Addition with Some Selected Nucleophiles" Heterocyclic Commun. 3(1). 19-22 (1997)

[Publications] He--ping Zeng: "Selective Formation of Mono- and Tetra-Cycloadducts by the Diels-Alder Reaction of[60]fullerene with 2,5-Dimethylthiophene S-Oxides" Synlett. (2). 175-176 (1997)

[Publications] Hiroyasu Tsuge: "Highly Diasteroselective Michael Addition to Optically Active Trifluoromethylated α、β-Unsaturated Sulfonamides Based on Their Hinge-Like Conformation" Tetrahedron. 53(3). 823-838 (1997)

[Publications] Bao-Xiang Zhau: "Synthesis of Nitrones from 3,4-Dihydroisoquinoline Derivatives by Oxidation with m-Chloropeoxybenzoic Acid" Org.Prep.& Proced.Int.29(2). 185-194 (1997)

[Publications] Yang Yu: "Synthesis of 2-Aza-3-oxatetracyclo[7.3.1.17,11.02,6]tetradecane Derivatives by the 1,3-Dipolar Cycloaddition Reaction of Homoadamantane-Incorporated Nitrones with Alkenes" Tetrahedron. 53(15). 5413-5422 (1997)

[Publications] Hiroyasu Tsuge: "Asymmetric 1,3-Dipolar Cycloaddition of Optically Active Trifluoromethylated α,β-Unsaturated Aryl Sulfones with Nitrones:the Use of o-Dialkylaminoethyl Chiral Auxiliaries" J.Chem.Soc.,Perkin Trans 1. (10). 1581-1586 (1997)

[Publications] Masatomi Ohno: "Synthesis of Heterocycle-Linked[60]Fullerene Derivatives by Heterocyclic o-Quinodimethane Diels-Alder Reaction and Self-Sensitized Photooxygenation of the Cycloadducts" Tetrahedron. 53(27). 9075-9086 (1997)

[Publications] Bao-Xiang Zhau: "1,3-Dipolar Cycloaddition Reaction of Substituted 3,4-Dihydroisoquinoline N-Oxides with Allenes" Tetrahedron. 53(28). 9575-9584 (1997)

[Publications] Toshiyuki Sugimori: "The First Total Synthesis of(-)-Benzomalvin A via Intramolecular Aza-Wittig Reaction" Chem.Lett.(9). 869-891 (1997)

[Publications] Masatomi Ohno: "スクアリン酸を合成素子とする多官能型炭素及び複素環化合物の高選択的合成" 有機合成化学協会誌. 55(9). 785-792 (1997)

[Publications] Takashi Okano: "Cyclization of Hindered Fluorinated Dichloro(5- and 6-)alkenyl Radicals.Structural Effects of Olefins on the Selective Formation of 5-exo and 6-endo Cyclization Products" J.Org.Chem.62(21). 7192-7200 (1997)

[Publications] Tomohiro Okwa: "One-pot Synthesis of Novel(2-Oxo-1,2-dihydropyridin-3-yl)-1,3,5-triazine Derivatives from Methyl 2-(N-Triphenylphosphoranlidene)aminonicotinate,Arylisocyanates and Primary Amines" Tetrahedron. 53(47). 16061-16082 (19997)

[Publications] Masatomi Ohno: "Fusion of C60 with Cyclic Amino Acid and Thiourea by Hetero Diels-Alder Reactions" Heterocycles. 46(1). 49-52 (1997)

[Publications] Shoji Eguchi: "Synthesis of Heterocycle-Containing[60]Fulleren Derivatives.II.Recent Progress in [4+2]-and[3+2]-Cycloaddition Routes,Eguchi" Fullerene Sci.& Tech.5(5). 977-987 (1997)

[Publications] Tomohiro Okwa: "Chemoselectivity in the Intramolecular Aza-ittig Reaction of N-[2-(Trisubstituted Phosphoranilylidene)aminobenzoyl]-2-pyridone-5-carboxylic Acid Derivatives." Heterocycles. 47(1). 375-382 (1998)

[Publications] Shoji Eguchi(分担執筆): "Synthesis of Heterocyclic Natural Products and Related Heterocycles by the Aza-Wittig Methodology in "Recent Research Developement in Organic Chemistry"" Transworld Research Network, 12/000 (1998)

[Publications] Shoji Eguchi(分担執筆): "Molecular Design of Novel Carbo- & Heteropolycycles based on Adamantane in "Recent Research Developement in Pure and Applied Chemistry"" Transworld Research Network, 12/000 (1998)

江口昇次名古屋大学, 工学研究科, 教授 (50023099)