1998 年度実績報告書

数種の生物活性天然物の触媒的不斉全合成

研究課題

研究課題/領域番号	10470462
研究種目	基盤研究(B)
研究機関	東京大学
研究代表者	柴崎正勝東京大学, 大学院・薬学系研究科, 教授 (30112767)
研究分担者	魚津公一郎東京大学, 大学院・薬学系研究科, 助手 (10282609) 金井求東京大学, 大学院・薬学系研究科, 助手 (20243264) 飯田剛彦東京大学, 大学院・薬学系研究科, 助手 (40292958)
キーワード	多機能不斉触媒 / ALB / マイケル反応 / ツビホリジン / 触媒的不斉ヘック反応 / ワートマンニン / 触媒的不斉分子内シクロプロパン化反応 / ホルボールエステル
研究概要	当研究室で開発した多機能不斉触媒ALBの制御によるマイケル反応を鍵工程として、20-デエチルツビホリジンとツビホリジンの触媒的不斉全合成を達成した。すなわち触媒的マイケル反応で得られた成績体(>99%ee)をフィッシャーインドール合成反応に付し、DDQによる酸化的環化反応によってツビホリジン類の持つ5つの環のうち4つを合成した。5つ目の環はジチオアセタールからのDMTSFによるカチオン種へのインドール環の求核反応により合成した。触媒的不斉へック反応を鍵工程とする、PI3キナーゼ阻害剤ワートマンニンの不斉全合成を目的として研究を行った。その結果20mol%のTol-BINAP-パラジウム錯体の制御によりラセミ体原料の速度論的分割が高エナンチオ選択的に進行し、鍵中間体であるヘック反応成績体が96%eeで得られることを見出した。触媒的不斉分子内シクロプロパン化反応により、プロテインキナーゼC活性化剤であるホルボールエステルの中間体を高収率、高エナンチオ選択的に達成した。

研究成果

(27件)

すべてその他

すべて文献書誌 (27件)

[文献書誌] T.Arai, H.Sasai, K.Yamaguchi and M.Shibasaki: "Regioselective Catalytic Asymmetric Reaction of Horner-Wadsworth-Emmons Reagents with Enones:The Odyssey of Chiral Aluminum Catalysts" J.Am.Chem.Soc.120. 441-442 (1998)
[文献書誌] M.Sodeoka, M.A.Arai, K.Adachi, K.Uotsu and M.Shibasaki: "Rational Design, Synthesis, and Evaluation of a New Type of PKC Inhibitor" J.Am.Chem.Soc.120. 457-458 (1998)
[文献書誌] S.Y.Cho and M.Shibasaki: "Synthesis and Evaluation of a New Chiral Ligand:2-diphenylarsino-2'-diphenylphosphino-1, 1'-binaphthyl(BINAPAs)" Tetrahedron Lett.39. 1773-1776 (1998)
[文献書誌] A.Kojima, T.Takemoto, M.Sodeoka and M.Shibasaki: "Catalytic Asymmetric Synthesis of Halenaquinone and Halenaquinol" Synthesis. 581-589 (1998)
[文献書誌] H.Groger, Y.Saida, H.Sasai, K.Yamaguchi, J.Martens and M.Shibasaki: "A New and Highly Efficient Asymmetric Route to Cyclic α-Amino Phosphonates:The First Catalytic Enantioselective Hydrophosphonylation of Cyclic Imines Catalyzed by Chiral Heterobimetallic Lanthanoid" J.Am.Chem.Soc.120. 3089-3103 (1998)
[文献書誌] E.Emori, T.Arai, H.Sasai and M.Shibasaki: "A Catalytic Michael Addition of Thiois to α, β-Unsaturated Carbonyl Compounds:Asymmetric Protonations" J.Am.Chem.Soc.120. 4043-4044 (1998)
[文献書誌] M.Shibasaki、 T.Iida Y.M.A.Yamada: "Development of Multifunctional Asymmetric Gatalysts and Their Application to Practical Organic-Synthesis" 有機合成化学協会誌. 56. 344-356 (1998)
[文献書誌] T.Morita, T.Arai, H.Sasai and M.Shibasaki: "Utilization of heterobimetallic complexes as Lewis acids" Tetrahedron:Asymmetry. 9. 1445-1450 (1998)
[文献書誌] M.Sodeoka and M.Shibasaki: "Asymmetric synthesis using palladium catalysts" Pure & Appl.Chem.70. 411-414 (1998)
[文献書誌] K.Yamada, T.Arai, H.Sasai and M.Shibasaki: "A Catalytic Asymmetric Synthesis of ll-Deoxy-PGF_<1α> Using ALB, a Heterobimetallic Multifunctional Asymmetric Complex" J.Org.Chem.63. 3666-3672 (1998)
[文献書誌] Y.M.A.Yamada and M.Shibasaki: "Direct Catalytic Asymmetric Aldol Reaction Promoted by a Novel Barium Complex" Tetrahedron Letters.39. 5561-5564 (1998)
[文献書誌] M.Shibasaki, H.Sasai, T.Arai and T.Iida: "Heterobimetallic asymmetric catalysts, Developments and applications" Pure & Appl.Chem.70. 1027-1034 (1998)
[文献書誌] M.Shibasaki and K.Uotsu: "PKC activations and inhibitors" IGAKUSHOIN. 49. 290-295 (1998)
[文献書誌] K.Uotsu, M.Sodeoka and M.Shibasaki: "Photoaffinity Labeling of PKC Isozymes by Phorbol Ester Derivatives" Bioorg.& Med.Chem.6. 1117-1126 (1998)
[文献書誌] H.Grber, E.M.Vogl and M.Shibasaki: "New Catalytic Concepts for the Asymmetric Aldol Reaction" Chem.Eur.J.4. 1137-1141 (1998)
[文献書誌] T.Iida, N.Yamamoto, H-G.Woo and M.Shibasaki: "Enantioselective Ring Opening of Epoxides with 4-Methoxyphenol Catalyzed by Gallium Heterobimetallic Complexes:An Efficient Method for the Synthesis of Optically Active 1, 2-Diol Monoethers" Angew.Chem.Int.Ed.Engl.37. 2223-2226 (1998)
[文献書誌] M.Shibasaki, H.Sasai, T.Arai and T.Iida: "Heterobimetallic asymmetric catalysts. Developments and applications" Pure & Appl.Chem.70. 1027-1034 (1998)
[文献書誌] E.M.Vogl, S.Matsunaga, M.Kanai, T.Iida and M.Shibasaki: "Linking BINOL:C_3-Symmetric Ligands for Investigations on Asymmetric Catalysis" Tetrahedron Letters. 39. 7917-7920 (1998)
[文献書誌] F.Miyazaki, K.Uotsu and M.Shibasaki: "Silver Salt Effects on an Asymmetric Heck Reaction. Catalytic Asymmetric Total Synthesis of(+)- Xestoquinone." Tetrahedron. 54. 13073-13078 (1998)
[文献書誌] S.Shimizu, K.Ohori, T.Arai, H.Sasai and M.Shibasaki: "A Catalytic Asymmetric Synthesis of Tubifolidine" J.Org.Chem.63. 7547-7551 (1998)
[文献書誌] K.Funabashi, Y.Saida, M.Kanai, T.Arai, H.Sasai and M.Shibasaki: "Catalytic Asymmetric Michael Adition of Nitromethane to Enones Controlled by(R)-LPB" Tetrahedron Letters. 39. 7557-7558 (1998)
[文献書誌] S.Watanabe, Y.Kobayashi, T.Arai, H.Sasai, M.Bougauchi and M.Shibasaki: "Water vs.Desiccant Improvement of Yb-BINOL Complex Catalyzed Enantioselective Epoxidation of Enones" Tetrahedron Letters. 39. 7353-7356 (1998)
[文献書誌] M.Shibasaki, A.Kojima and S.Shimizu: "Catalytic Asymmetric Synthesis of Natural Products with Heterocyclic Rings" J.Heterocyclic Chem.35. 1057-1064 (1998)
[文献書誌] S.Watanabe, T.Arai, H.Sasai, M.Bougauchi and M.Shibasaki: "The First Catalytic Enatioselective Synthesis of cis-Epoxyketones from cis-Enones" J.Org.Chem.63. 8090-8091 (1998)
[文献書誌] S.Y.Cho and M.Shibasaki: "The symmetric synthesis of cyclopentane derivaties by palladium-cataluzed coupling of prochiral alkylboron compounds" Tetrahedron:Asymmetry. 9. 3751-3754 (1998)
[文献書誌] S.Yamasaki, T.Iida and M.Shibasaki: "Direct Catalytic Asymmetric Mannich-type Reaction of Unmodified Ketones Utilizing the Cooperation of an AlLibis(binaphthoxide)Complex and La(OTI)_3,-nH_2O" Tetrahedron Lett.40. 307-310 (1999)
[文献書誌] S.Honzawa, T.Mizutani and M.Shibasaki: "Synthetic Studies on(+)-Wortmannin. An Asymmetric Construction of an Allylic Quaternary Carbon Center by a Heck Reaction" Tetrahedron Lett.40. 311-314 (1999)

1998 年度 実績報告書

数種の生物活性天然物の触媒的不斉全合成

研究代表者

柴崎 正勝 東京大学, 大学院・薬学系研究科, 教授 (30112767)

研究成果

[文献書誌] T.Arai, H.Sasai, K.Yamaguchi and M.Shibasaki: "Regioselective Catalytic Asymmetric Reaction of Horner-Wadsworth-Emmons Reagents with Enones:The Odyssey of Chiral Aluminum Catalysts" J.Am.Chem.Soc.120. 441-442 (1998)

[文献書誌] M.Sodeoka, M.A.Arai, K.Adachi, K.Uotsu and M.Shibasaki: "Rational Design, Synthesis, and Evaluation of a New Type of PKC Inhibitor" J.Am.Chem.Soc.120. 457-458 (1998)

[文献書誌] S.Y.Cho and M.Shibasaki: "Synthesis and Evaluation of a New Chiral Ligand:2-diphenylarsino-2'-diphenylphosphino-1, 1'-binaphthyl(BINAPAs)" Tetrahedron Lett.39. 1773-1776 (1998)

[文献書誌] A.Kojima, T.Takemoto, M.Sodeoka and M.Shibasaki: "Catalytic Asymmetric Synthesis of Halenaquinone and Halenaquinol" Synthesis. 581-589 (1998)

[文献書誌] E.Emori, T.Arai, H.Sasai and M.Shibasaki: "A Catalytic Michael Addition of Thiois to α, β-Unsaturated Carbonyl Compounds:Asymmetric Protonations" J.Am.Chem.Soc.120. 4043-4044 (1998)

[文献書誌] M.Shibasaki、 T.Iida Y.M.A.Yamada: "Development of Multifunctional Asymmetric Gatalysts and Their Application to Practical Organic-Synthesis" 有機合成化学協会誌. 56. 344-356 (1998)

[文献書誌] T.Morita, T.Arai, H.Sasai and M.Shibasaki: "Utilization of heterobimetallic complexes as Lewis acids" Tetrahedron:Asymmetry. 9. 1445-1450 (1998)

[文献書誌] M.Sodeoka and M.Shibasaki: "Asymmetric synthesis using palladium catalysts" Pure & Appl.Chem.70. 411-414 (1998)

[文献書誌] K.Yamada, T.Arai, H.Sasai and M.Shibasaki: "A Catalytic Asymmetric Synthesis of ll-Deoxy-PGF_<1α> Using ALB, a Heterobimetallic Multifunctional Asymmetric Complex" J.Org.Chem.63. 3666-3672 (1998)

[文献書誌] Y.M.A.Yamada and M.Shibasaki: "Direct Catalytic Asymmetric Aldol Reaction Promoted by a Novel Barium Complex" Tetrahedron Letters.39. 5561-5564 (1998)

[文献書誌] M.Shibasaki, H.Sasai, T.Arai and T.Iida: "Heterobimetallic asymmetric catalysts, Developments and applications" Pure & Appl.Chem.70. 1027-1034 (1998)

[文献書誌] M.Shibasaki and K.Uotsu: "PKC activations and inhibitors" IGAKUSHOIN. 49. 290-295 (1998)

[文献書誌] K.Uotsu, M.Sodeoka and M.Shibasaki: "Photoaffinity Labeling of PKC Isozymes by Phorbol Ester Derivatives" Bioorg.& Med.Chem.6. 1117-1126 (1998)

[文献書誌] H.Grber, E.M.Vogl and M.Shibasaki: "New Catalytic Concepts for the Asymmetric Aldol Reaction" Chem.Eur.J.4. 1137-1141 (1998)

[文献書誌] T.Iida, N.Yamamoto, H-G.Woo and M.Shibasaki: "Enantioselective Ring Opening of Epoxides with 4-Methoxyphenol Catalyzed by Gallium Heterobimetallic Complexes:An Efficient Method for the Synthesis of Optically Active 1, 2-Diol Monoethers" Angew.Chem.Int.Ed.Engl.37. 2223-2226 (1998)

[文献書誌] M.Shibasaki, H.Sasai, T.Arai and T.Iida: "Heterobimetallic asymmetric catalysts. Developments and applications" Pure & Appl.Chem.70. 1027-1034 (1998)

[文献書誌] E.M.Vogl, S.Matsunaga, M.Kanai, T.Iida and M.Shibasaki: "Linking BINOL:C_3-Symmetric Ligands for Investigations on Asymmetric Catalysis" Tetrahedron Letters. 39. 7917-7920 (1998)

[文献書誌] F.Miyazaki, K.Uotsu and M.Shibasaki: "Silver Salt Effects on an Asymmetric Heck Reaction. Catalytic Asymmetric Total Synthesis of(+)- Xestoquinone." Tetrahedron. 54. 13073-13078 (1998)

[文献書誌] S.Shimizu, K.Ohori, T.Arai, H.Sasai and M.Shibasaki: "A Catalytic Asymmetric Synthesis of Tubifolidine" J.Org.Chem.63. 7547-7551 (1998)

[文献書誌] K.Funabashi, Y.Saida, M.Kanai, T.Arai, H.Sasai and M.Shibasaki: "Catalytic Asymmetric Michael Adition of Nitromethane to Enones Controlled by(R)-LPB" Tetrahedron Letters. 39. 7557-7558 (1998)

[文献書誌] S.Watanabe, Y.Kobayashi, T.Arai, H.Sasai, M.Bougauchi and M.Shibasaki: "Water vs.Desiccant Improvement of Yb-BINOL Complex Catalyzed Enantioselective Epoxidation of Enones" Tetrahedron Letters. 39. 7353-7356 (1998)

[文献書誌] M.Shibasaki, A.Kojima and S.Shimizu: "Catalytic Asymmetric Synthesis of Natural Products with Heterocyclic Rings" J.Heterocyclic Chem.35. 1057-1064 (1998)

[文献書誌] S.Watanabe, T.Arai, H.Sasai, M.Bougauchi and M.Shibasaki: "The First Catalytic Enatioselective Synthesis of cis-Epoxyketones from cis-Enones" J.Org.Chem.63. 8090-8091 (1998)

[文献書誌] S.Y.Cho and M.Shibasaki: "The symmetric synthesis of cyclopentane derivaties by palladium-cataluzed coupling of prochiral alkylboron compounds" Tetrahedron:Asymmetry. 9. 3751-3754 (1998)

[文献書誌] S.Yamasaki, T.Iida and M.Shibasaki: "Direct Catalytic Asymmetric Mannich-type Reaction of Unmodified Ketones Utilizing the Cooperation of an AlLibis(binaphthoxide)Complex and La(OTI)_3,-nH_2O" Tetrahedron Lett.40. 307-310 (1999)

[文献書誌] S.Honzawa, T.Mizutani and M.Shibasaki: "Synthetic Studies on(+)-Wortmannin. An Asymmetric Construction of an Allylic Quaternary Carbon Center by a Heck Reaction" Tetrahedron Lett.40. 311-314 (1999)

1998 年度実績報告書

柴崎正勝東京大学, 大学院・薬学系研究科, 教授 (30112767)