1998 Fiscal Year Annual Research Report

数種の生物活性天然物の触媒的不斉全合成

Research Project

Project/Area Number	10470462
Research Category	Grant-in-Aid for Scientific Research (B)
Research Institution	The University of Tokyo
Principal Investigator	柴崎正勝東京大学, 大学院・薬学系研究科, 教授 (30112767)
Co-Investigator(Kenkyū-buntansha)	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)
Keywords	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
Research Abstract	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。

Research Products
(27 results)

All Other

All Publications (27 results)

[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] A.Kojima, T.Takemoto, M.Sodeoka and M.Shibasaki: "Catalytic Asymmetric Synthesis of Halenaquinone and Halenaquinol" Synthesis. 581-589 (1998)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] T.Morita, T.Arai, H.Sasai and M.Shibasaki: "Utilization of heterobimetallic complexes as Lewis acids" Tetrahedron:Asymmetry. 9. 1445-1450 (1998)
[Publications] M.Sodeoka and M.Shibasaki: "Asymmetric synthesis using palladium catalysts" Pure & Appl.Chem.70. 411-414 (1998)
[Publications] 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)
[Publications] Y.M.A.Yamada and M.Shibasaki: "Direct Catalytic Asymmetric Aldol Reaction Promoted by a Novel Barium Complex" Tetrahedron Letters.39. 5561-5564 (1998)
[Publications] M.Shibasaki, H.Sasai, T.Arai and T.Iida: "Heterobimetallic asymmetric catalysts, Developments and applications" Pure & Appl.Chem.70. 1027-1034 (1998)
[Publications] M.Shibasaki and K.Uotsu: "PKC activations and inhibitors" IGAKUSHOIN. 49. 290-295 (1998)
[Publications] K.Uotsu, M.Sodeoka and M.Shibasaki: "Photoaffinity Labeling of PKC Isozymes by Phorbol Ester Derivatives" Bioorg.& Med.Chem.6. 1117-1126 (1998)
[Publications] H.Grber, E.M.Vogl and M.Shibasaki: "New Catalytic Concepts for the Asymmetric Aldol Reaction" Chem.Eur.J.4. 1137-1141 (1998)
[Publications] 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)
[Publications] M.Shibasaki, H.Sasai, T.Arai and T.Iida: "Heterobimetallic asymmetric catalysts. Developments and applications" Pure & Appl.Chem.70. 1027-1034 (1998)
[Publications] 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)
[Publications] 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)
[Publications] S.Shimizu, K.Ohori, T.Arai, H.Sasai and M.Shibasaki: "A Catalytic Asymmetric Synthesis of Tubifolidine" J.Org.Chem.63. 7547-7551 (1998)
[Publications] 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)
[Publications] 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)
[Publications] M.Shibasaki, A.Kojima and S.Shimizu: "Catalytic Asymmetric Synthesis of Natural Products with Heterocyclic Rings" J.Heterocyclic Chem.35. 1057-1064 (1998)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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 Fiscal Year Annual Research Report

数種の生物活性天然物の触媒的不斉全合成

Principal Investigator

柴崎 正勝 東京大学, 大学院・薬学系研究科, 教授 (30112767)

Research Products

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

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

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

[Publications] 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)

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

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

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

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

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

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

柴崎正勝東京大学, 大学院・薬学系研究科, 教授 (30112767)