1997 Fiscal Year Annual Research Report

高次構造構築法の開発

Research Project

Project/Area Number	08245101
Research Institution	The University of Tokyo
Principal Investigator	奈良坂紘一東京大学, 大学院・理学系研究科 (50016151)
Co-Investigator(Kenkyū-buntansha)	宮下正昭北海道大学, 大学院・理学研究科, 教授 (50006326) 冨士薫京都大学, 化学研究所, 教授 (20027056) 橋本俊一北海道大学, 薬学部, 教授 (80107391) 竜田邦明早稲田大学, 大学院・理工学研究科, 教授 (40051627) 北泰行大阪大学, 薬学部, 教授 (00028862)
Keywords	オキシム / イソキノリン / 超原子価ヨウ素試剤 / 分子内Diels-Alder反応 / 分子内CH挿入反応 / 不斉ニトロオレフィン化 / ヌクレオチド結合生成反応
Research Abstract	本研究では,現在その生理活性や特異的な構造が注目を集めている代表的な高次構造天然有機化合物を視野におき,これらの化合物の基本炭素骨格の構築,あるいはその立体化学の制御を可能とする新しい合成手法を開発することを目的とし研究を行った。具体的な成果を以下に示す。・オキシム窒素原子上での置換反応を利用しイソキノリンあるいはテトラヒドロイソキノリン骨格の簡便な構築法を確立した。さらにこの手法をデヒドロピロリジン骨格の構築にも利用できることを見出した。・超原子価ヨウ素試剤を用いるインドロキノンイミン骨格構築法を確立し,これを利用しDiscorhabdinの合成を検討した。またFredericamycinの部分合成を達成した。・分子内のDiels-Alder反応を鍵としてCalbistrinの全合成を達成し,その絶対構造を明らかにすることができた。また,黄体ホルモン受容体リガンドのPF1092類を大量の合成する方法を実現した。・キラルなロジウム(II)錯体触媒を用い分子内C-H挿入反応を行い4-置換-2-ピロリジノンの触媒的不斉合成を達成した。またカルボニルイリドの不斉1,3双極子環化反応を実現した。・3-置換-2-オキシインドールの不斉ニトロオレフィン化により四級不斉炭素を高エナンチオ選択的に構築する方法を確立し,ホルスフィリンの全合成を達成した。・γ,δ-エポキシアクリル酸エステルを利用した連続不斉中心を有する不斉四級炭素構築法を確立した。・新しい強力な脱水縮合剤BOMPを用い塩基部位を全く保護する必要のないインターヌクレオチド結合生成反応を行う手法を確立し,実践的なDNA,RNAの化学合成法を開発することができた。

Research Products

(21 results)

All Other

All Publications (21 results)

[Publications] H.Tsutsui: "Preparation of Primary Amines by the Copper(1)Catalyzed Reaction of 4,4′-Bis(trifluoromethyl)benzophenone O-Methylsulfonyoxime and Alkyl Grignard Reagents." Chem.Lett.317-318 (1997)
[Publications] H.Kusama: "Transformation of Oximes of Phenethyl Ketone Derivatives,to Quinolines and Azaspirotrienones Catalyzed by Tetrabutylammonium Perrhenate and Trifluoromathanesulfonic Acid." Bull.Chem.Soc.Jpn.70. 965-975 (1997)
[Publications] K.Uchiyama: "Synthesis of 8-Hydroxyquinolines by the Cyclization of m-Hydroxyphenethyl Ketone O-2,4-Dinitrophenyloximes." Synlett. 445-446 (1997)
[Publications] M.Suzuki: "Substituent Effect of 1,4-Benzenedicarbonitriles as Sensitizers on the Photoinduced Electron Transfer Reaction in Alcohol." Bull.Chem.Soc.Jpn.70. 2269-2277 (1997)
[Publications] S.Mori: "S_N2 Substitution on sp^2 Nitrogen of Protonated Oxime." Chem.Lett.111-112 (1998)
[Publications] Y.Kita: "Isolation of the Quinone Mono O,S-Acetal Intermediates of the Aromatic Pummerer-Type Rearrangement fo the p-Sulfinylphenols with 1-Ethoxyvinyl Esters." Angew.Chem.Int.Ed.Engl.1529-1531 (1997)
[Publications] S.Akai: "Novel ipso-Substitution of p-Sulfinyl phenols Through the Pummerer-Type Reaction:A Selective and Efficient Synthesis of p-Quinones and Protected p-Dihydroquinones." J.Org.Chem.5526-5536 (1997)
[Publications] Y.Kita: "Acid-Promoted Rearrangement of Cyclic a,b-Epoxy Acylates:Stereoselective Synthesis of Spirocyclanes and Quaternary Carbon Centers." J.Org.Chem.4991-4997 (1997)
[Publications] T.Wada: "Chemical Synthesis of Oligodexyribonucleotides Using N-Unprotected H-Phosphonate Monomers and Carbonium and Phosphonium Condensing Reagents:O-Selective Phosphonylation and Condensation." J.Am.Chem.Soc.119. 12710-12721 (1997)
[Publications] H.Tsuruoka: "Kinetics and Mechanism of Facile and Selective Dephosphorylation and of 2′-Phosphorylated and 2-Thiophosphorylated Dinucleotides:Neoghboring 3′-5′ Phosphodiester Promoters 2′-Dephosphorylation." J.Org.Chem.62. 2813-2811 (1997)
[Publications] T.Wada: "Stereocontrolled Synthesis of Dithymidine Phorothioates by Use of a Functionslized 5′-Protecting Group Bearing an Imidazole Residue." Nucleosides Nucleotides. 16. 1023-1032 (1998)
[Publications] K.Tatsuta: "The first total synthesis of calbistrin A,a microbial product possessing multiple bioactivities." Tetrahedron Lett.38. 583-586 (1997)
[Publications] K.Tatsuta: "Total synthesis of progestereo receptor ligands,(-)-PF1092A,B and C." Tetrahedron Lett.38. 1439-1442 (1997)
[Publications] K.Tatsuta: "The total synthesis of a glycosidase inhibitor,nagstatin." Tetrahedron Lett.39. 83-86 (1998)
[Publications] S.Kitagaki: "Highly Ensntioselective Intermolecular Cyclopropanation Catalyzed Dkirhodium(E)Tetrakis[3(S)-phthalimido-2-piperidonate]:Solvent Dependency of the Enantioselection." Synlett. 1171-174 (1997)
[Publications] M.Anada: "Enantioselective synthesis of 4-Substituted 2-Pyrrolidinones by Site-selective C-H Insertion of a Methoxycarbonyl-a-diazoacetanilides Catalyzed by Dirhodium(II)Tetrakis[N-phthaloyl-(S)-tert-leucinate]" Tetrahedron Lett.39. 79-82 (1997)
[Publications] H.Sato: "Total Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C." Synlett. 451-454 (1997)
[Publications] K.Fuji: "Enantioselective Creation of Quarternary Carbon Centers through Addition-Elimination Reaction:Asymmetric Nitroolefination of 3-Substituted 2-Oxindoles." Heterocycles. (印刷中).
[Publications] M.Miyashita: "The Efficient and Regioselective Synthesis of the Naphoquinone Core of Streptovaricin U." J.Chem.Soc.,Chem.Commun. 1787-1788 (1997)
[Publications] M.Miyashita: "Stereoselective Synthesis of the C1-C7 Segment of (+)-Discodermolide." Chem.Lett.1191-1192 (1997)
[Publications] M.Miyazawa: "Synthesis of the C8-C15 Segment of (+)-Discodermolide." Chem.Lett.1193-1194 (1997)

1997 Fiscal Year Annual Research Report

高次構造構築法の開発

Principal Investigator

奈良坂 紘一 東京大学, 大学院・理学系研究科 (50016151)

Research Products

[Publications] H.Tsutsui: "Preparation of Primary Amines by the Copper(1)Catalyzed Reaction of 4,4′-Bis(trifluoromethyl)benzophenone O-Methylsulfonyoxime and Alkyl Grignard Reagents." Chem.Lett.317-318 (1997)

[Publications] H.Kusama: "Transformation of Oximes of Phenethyl Ketone Derivatives,to Quinolines and Azaspirotrienones Catalyzed by Tetrabutylammonium Perrhenate and Trifluoromathanesulfonic Acid." Bull.Chem.Soc.Jpn.70. 965-975 (1997)

[Publications] K.Uchiyama: "Synthesis of 8-Hydroxyquinolines by the Cyclization of m-Hydroxyphenethyl Ketone O-2,4-Dinitrophenyloximes." Synlett. 445-446 (1997)

[Publications] M.Suzuki: "Substituent Effect of 1,4-Benzenedicarbonitriles as Sensitizers on the Photoinduced Electron Transfer Reaction in Alcohol." Bull.Chem.Soc.Jpn.70. 2269-2277 (1997)

[Publications] S.Mori: "S_N2 Substitution on sp^2 Nitrogen of Protonated Oxime." Chem.Lett.111-112 (1998)

[Publications] Y.Kita: "Isolation of the Quinone Mono O,S-Acetal Intermediates of the Aromatic Pummerer-Type Rearrangement fo the p-Sulfinylphenols with 1-Ethoxyvinyl Esters." Angew.Chem.Int.Ed.Engl.1529-1531 (1997)

[Publications] S.Akai: "Novel ipso-Substitution of p-Sulfinyl phenols Through the Pummerer-Type Reaction:A Selective and Efficient Synthesis of p-Quinones and Protected p-Dihydroquinones." J.Org.Chem.5526-5536 (1997)

[Publications] Y.Kita: "Acid-Promoted Rearrangement of Cyclic a,b-Epoxy Acylates:Stereoselective Synthesis of Spirocyclanes and Quaternary Carbon Centers." J.Org.Chem.4991-4997 (1997)

[Publications] T.Wada: "Chemical Synthesis of Oligodexyribonucleotides Using N-Unprotected H-Phosphonate Monomers and Carbonium and Phosphonium Condensing Reagents:O-Selective Phosphonylation and Condensation." J.Am.Chem.Soc.119. 12710-12721 (1997)

[Publications] H.Tsuruoka: "Kinetics and Mechanism of Facile and Selective Dephosphorylation and of 2′-Phosphorylated and 2-Thiophosphorylated Dinucleotides:Neoghboring 3′-5′ Phosphodiester Promoters 2′-Dephosphorylation." J.Org.Chem.62. 2813-2811 (1997)

[Publications] T.Wada: "Stereocontrolled Synthesis of Dithymidine Phorothioates by Use of a Functionslized 5′-Protecting Group Bearing an Imidazole Residue." Nucleosides Nucleotides. 16. 1023-1032 (1998)

[Publications] K.Tatsuta: "The first total synthesis of calbistrin A,a microbial product possessing multiple bioactivities." Tetrahedron Lett.38. 583-586 (1997)

[Publications] K.Tatsuta: "Total synthesis of progestereo receptor ligands,(-)-PF1092A,B and C." Tetrahedron Lett.38. 1439-1442 (1997)

[Publications] K.Tatsuta: "The total synthesis of a glycosidase inhibitor,nagstatin." Tetrahedron Lett.39. 83-86 (1998)

[Publications] S.Kitagaki: "Highly Ensntioselective Intermolecular Cyclopropanation Catalyzed Dkirhodium(E)Tetrakis[3(S)-phthalimido-2-piperidonate]:Solvent Dependency of the Enantioselection." Synlett. 1171-174 (1997)

[Publications] M.Anada: "Enantioselective synthesis of 4-Substituted 2-Pyrrolidinones by Site-selective C-H Insertion of a Methoxycarbonyl-a-diazoacetanilides Catalyzed by Dirhodium(II)Tetrakis[N-phthaloyl-(S)-tert-leucinate]" Tetrahedron Lett.39. 79-82 (1997)

[Publications] H.Sato: "Total Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C." Synlett. 451-454 (1997)

[Publications] K.Fuji: "Enantioselective Creation of Quarternary Carbon Centers through Addition-Elimination Reaction:Asymmetric Nitroolefination of 3-Substituted 2-Oxindoles." Heterocycles. (印刷中).

[Publications] M.Miyashita: "The Efficient and Regioselective Synthesis of the Naphoquinone Core of Streptovaricin U." J.Chem.Soc.,Chem.Commun. 1787-1788 (1997)

[Publications] M.Miyashita: "Stereoselective Synthesis of the C1-C7 Segment of (+)-Discodermolide." Chem.Lett.1191-1192 (1997)

[Publications] M.Miyazawa: "Synthesis of the C8-C15 Segment of (+)-Discodermolide." Chem.Lett.1193-1194 (1997)

奈良坂紘一東京大学, 大学院・理学系研究科 (50016151)