高次構造構築法の開発

• Project/Area Number: 08245101
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas (A)
• Allocation Type: Single-year Grants
• 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, 教授 (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・総合薬学科, 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)
• Project Period (FY): 1996 – 1998
• Project Status: Completed (Fiscal Year 1998)
• Budget Amount: ¥139,900,000 (Direct Cost: ¥139,900,000); Fiscal Year 1998: ¥35,500,000 (Direct Cost: ¥35,500,000); Fiscal Year 1997: ¥39,600,000 (Direct Cost: ¥39,600,000); Fiscal Year 1996: ¥64,800,000 (Direct Cost: ¥64,800,000)
• Keywords: オキシム窒素原子上での置換反応 / 不斉分子内C-H挿入反応 / 超原子価ヨウ素化合物 / 不斉1,3双極環化反応 / 不斉ニトロオレフィン化反応 / 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 / チランダマイシンB / ヘミブレベトキシンB / 脱水縮合剤 / インドールアルカロイド / キノリン

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。本年度はその最終年度であり,各班員がこれまでの成果をもとに,高次構造天然化合物の合成を検討した。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含窒素複素環化合物の合成法として確立し,これを利用して,Xenovenineの全合成を達成した。・エポキシアシラートの骨格転位反応と,多環性化合物間のDiels-Alder反応を鍵反応として,Fredericamycinの不斉全合成を達成した。また,超原子価ヨウ素試薬によるキノンイミン合成反応をもとに,Makaluvamineの全合成にも成功した。・新しい15員環形成反応を開発し抗HIV活性を有する(+)-Terpestacinの全合成を達成した。・キラルなロジウム(II)錯体触媒を用い不斉分子内C-H挿入反応を実現し,ホスホジエステラーゼ阻害剤の全合成に成功した。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,これを用いてZaragozic Acidのコア部分の立体選択的な合成を行った。・不斉ニトロオレフィン化反応を確立し,これを用いてSpirotryptostatin Bの基本骨格の構築を行った。・γ,δ-エポキシアクリル酸エステルを利用した不斉第四級炭素構築法をもとに,Scytophycin Cの合成を検討した。・mRNAのプロセッシングに必要な3'部位がbiotin標識されたU1RNAの5'末端部位の合成を行い,これを活用して核膜透過シグナルタンパクの単離同定に成功した。・酒石酸エステルを不斉源として用いる不斉1,3-双極子付加環化反応を利用して,Lasubine IIの合成を行った。

Research Products

• [Publications] 奈良坂 紘 一: "Synthesis of Dihydropyrroles and Tetrahydropyridines by the Intramolecular Cyclization of θ-Methylsulfonyloximes Having an Active Methine Group" Chem.Lett.607-608 (1998)
• [Publications] 奈良坂 紘 一: "Synthesis of Dihydropyrroles by the Intramolecular Addition of Alkyldeneaminyl Radicals Generated from θ-2,4-Dinitrophenyloximes of γ,δ-Unsaturated Ketones" Chem.Lett.1261-1262 (1998)
• [Publications] 奈良坂 紘 一: "Synthesis of Pyrrole Derivatives by the Heck-Type Cyclization of γ,δ-Unsaturated Ketone θ-Pentrafluorobenzoyloximes" Chem.Lett.45-46 (1999)
• [Publications] 北 泰行: "An Efficient Synthesis of peri-Hydroxy Aromatic Compounds: A Strong Base-Induced [4+2]Cycloaddition of 4-Phenylthio-Substituted Homophthalic Anhydrides with Various Sulfinyl-Substituted Dienophiles" Synlett. 292- (1998)
• [Publications] 北 泰行: "A Novel and Direct a-Azidation of Cyclic Sulfides Using a Hypervalent Iodine(III)Reagent" Chem.Commun.143- (1998)
• [Publications] 北 泰行: "A Novel and Efficient Synthesis of Pyrroloiminoquinone Using a Hypervalent Iodine(III)Reagent" J.Chem.Soc.,Perkin Trans 1. 635- (1998)
• [Publications] 関根 光雄: "Chemical synthesis and properties of conformationally fixed diuridine monophosphates as building blocks of RNA turn motif" J.Org.Chem.63. 1429-1443 (1998)
• [Publications] 関根 光雄: "Snurportin 1,an m3G-cap-specific nuclear import receptor with a novel domain structure" EMBO J.17. 4114-4126 (1998)
• [Publications] 関根 光雄: "Synthesis of new aminoacyl-adenylate analogs having an N-acyl phosphoramidate linkage" Tetrahedron Lett.39. 3725-3728 (1998)
• [Publications] 竜田 邦明: "The first total synthesis of a bioxanthracene (-)-ES-242-4,an N-methyl-D-aspartate receptor antagonist" Tetrahedron Lett.39. 1771-1774 (1998)
• [Publications] 竜田 邦明: "Synthesis and biological evaluation of the analogs of bioxanthracenes ES-242s,N-methyl-D-aspartate antagonists" J.Antibiot.51(3). 383-386 (1998)
• [Publications] 竜田 邦明: "The first total synthesis of natural (+)-terpestacin,Syncytium formation inhibitor" J.Antibiot.51(6). 602-606 (1998)
• [Publications] 橋本 俊一: "Enantioselective Synthesis of 4-Substituted 2-Pyrrolidinones by Site-selective C-H Insertion of a-Methoxycarbonyl-a-diazoacetanilides Catalyzed by Dirhodium(II) Tetrakis [N-phthaloy-(S)tert-leucinate]" Tetrahedron Lett.39. 79-82 (1998)
• [Publications] 橋本 俊一: "Toward the Second-Generation Synthesis of Zaragozic Acids : Construction of the 2,8-Dioxabicyclo[3.2.1]octane Core System via Tandem Carbonyl Ylide Formation and 1,3-Dipolar Cycloaddition Sequence" Tetrahedron Lett.39. 2371-2374 (1998)
• [Publications] 橋本 俊一: "Enantioselective Intramolecular C-II Insertion Route to a Key Intermediate for the Synthesis of Trinem Antibiotics" Tetrahedron Lett.39. 9063-9066 (1998)
• [Publications] 冨士 薫: "Enantioselective Creation of Quartenary Carbon Centers through Addition-Elimination Reaction" Heterocycles. 47. 951-964 (1998)
• [Publications] 冨士 薫: "The First Synthesis of an Optically Active Molecular Bevel Gear with Only Two Cogs on Each Wheel" Tetrahedron Lett.39. 1373-1376 (1998)
• [Publications] 冨士 薫: "Palladium-Catalyzed Asymmetric Reduction of Allylic Esters with a New Chiral Mondentate Ligard,8-Diphenylphosphosphino-8'-methoxy-1,1'-binaphthyl" Tetrahedron Lett.39. 6323-6326 (1998)
• [Publications] 宮下 正昭: "Effficient and Stereospecific Construction of Asymmetric Quaternary Carbons via g-Alkyl-g,d-epoxy Acrylates" Tetrahedron Lett.39. 3775-3778 (1998)
• [Publications] 宮下 正昭: "Highly Stereoselective Epoxidation of a 4-Methyl-5(triethylsilyl) oxyallyl Alcohol System with m-Chloroperoxybenzoic Acid" Tetrahedron Lett.39. 4517-4520 (1998)
• [Publications] 宮下 正昭: "Expeditious and Stereoselective Synthesis of Chiral trans b-Hydroxy-d-lactone Systems" Chem.Lett.109-110 (1998)
• [Publications] 猪股 勝彦: "Enantio-and Diastereoselective Synthesis of Isoxazolidines by Asymmetric 1,3-DIpolar Cycloaddition of Nitrones" Chem.Lett.547-548 (1997)
• [Publications] 猪股 勝彦: "酒石酸エステルを活用する不斉付加環化反応および不斉求核付加反応" 有機合成化学協会誌. 56. 11-21 (1998)
• [Publications] 猪股 勝彦: "Development of New Asymmetric Reactions Utilizing Tartaric Acid Ester as a Chiral Auxiliary : Design of an Efficient Chiral Dinucleating System" Review on Heteroatom Chemistry. 18. 119-140 (1998)
• [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)
• [Publications] Y.Kohno: "Synthesis of (±)-Stemonamide by the Application of Oxidative Coupling Reactions of Stamyl Compounds with Silyl Enol Ethers." Bull.Chem.Soc.Jpn.69. 2063-2070 (1996)
• [Publications] K.Uchiyama: "Synthesis of 8-Hydroxyqinolines by the Cyclization of m-Hydroxyphenethyl Ketone 0-2,4-Dinitrophenyloximes." Synlett. (印刷中). (1997)
• [Publications] H.Tsutsui: "Preparation of Primary Amines by the Copper(1)Catalyzed Renction of 4,4′-Bis(trifluoromethyl)benzophenone O-Methylsufomloxime and Alkyl Grignard Reagents." Chemistry Letters. (印刷中). (1997)
• [Publications] Y.Kita: "Novel and Efficient Synthesis of Sulfur-containing Heterocycles using Hypervalent lodine(III)Reagent." J.Chem.Soc.Chem.Commun. 2225-2226 (1996)
• [Publications] Y.Kita: "Asymmetric Synthesis of Chiral Spirocyclanes:A New Route to the Optically Active Spiro[cyclopentane-1,1′-indan]-2,5-dione System." Tetrahedron Lett.37. 1817-1820 (1996)
• [Publications] Y.Kita: "Hyperavalent lodine(III)Induced Intramolecular Cyclization of substituted Phenol Ethers bearing an Alkyl Azide Sidechain-A Novel synthesis of Quinone Imine Ketals." J.Chem.Soc.Chem.Commun.1491-1492 (1996)
• [Publications] S.Kawahara: "1:1 and 1:2 Complexes of Bu_4NF and BF_3Et_2O:New Reagents for Rapid Cleavage of Silyl Ethers." Tetrahedron.Lett.37. 509-512 (1996)
• [Publications] K.Seio: "Chemical Synthesis and Conformational Properties of a New Cyclouridylic acid Having an Ethylene Bridge between the Uracil 5-Position and 5′-Phosphate Group." J.Org.Chem.61. 1500-1504 (1996)
• [Publications] M.Sekine: "The Chemical Synthesis of 5′-Terminal TMG-Capped Triribonucleotide m_3^<2.2.7.>G^5pppAmpUmpA of Ul RMA." J.Org.Chem.61. 4412-4422 (1996)
• [Publications] K.Tatsuta: "Total synthesis of deacetyl-caloporoside,a novel inhibitor of the GABAA receptor ion channel." Tetrahedron Lett.37. 2453-2456 (1996)
• [Publications] K.Tatsuta: "Total synthesis and chemical dasign of useful glycosidase inhibitors." Pure & Appl.Chem.68. 1341-1346 (1996)
• [Publications] K.Tatsuta: "Synthesis and Biological Evaluation of Caloporoside Analogs." J.Antibiot.49. 713-715 (1996)
• [Publications] T.Shiratani: "A Stereocontrolled Enantiospecific Route to Tirandamycin B." J.Chem.Soc.Chem.Commun.21-22 (1996)
• [Publications] M.Miyashita: "Tandem Synthesis of Polypropionate Chains-Highly Stereoseiective Synthesis of Ansa Chain of Streptovaricin U and Protostreptovaricins Besed on Stereospecific Methylation of γ,δ-Epoxy Acrylates by Trimethylaluminnm." J.Chem.Soc.Chem.Commmun.1027-1028 (1996)
• [Publications] 宮下正昭: "ジョロウグモ(Nephila clavata)の毒素Nephilatoxin類の合成研究" 有機合成化学協会誌. 54-10. 846-858 (1996)
• [Publications] I.Kadota: "Novel Route to the Synthesis of Hdroxylated Piperdine and Pyrrolidine Derivatives via the Intramolecular Reaction of γ-Aminoallylstannane with Aldehyde." Tetrahedron Lett.37. 2109-2112 (1996)
• [Publications] I.Kadota: "Intramolecular Reaction of γ-Alkoxyallylstannane with Hydrazone:Stereoselective Synthesis of β-Aminoterahydropyran and -furan." J.Chem.Soc.Chem.Commun.841-842 (1996)
• [Publications] I.Kadota: "Intramolecular Reaction of Oxo-Substituted Allenyl-and Propargylstannane with Aldehyde." Tetrahedron Lett.37. 3059-3062 (1996)