1999 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 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)
Keywords	多機能不斉触媒 / エポシロン / ジヒドロアクアマイシン / 触媒的不斉シアノシリル化反応 / 直接的触媒的不斉アルドール反応 / 触媒的分割 / 触媒的不斉マイケル反応
Research Abstract	当研究室で開発した多機能不斉触媒を鍵行程として、抗腫瘍活性天然物エポシロン類、Strychnosアルカロイド19,20-ジヒドロアクアマイシンの触媒的不斉全合成を達成した。抗腫瘍活性天然物エポシロン類の合成では、アルミニウムを中心金属とするルイス酸-ルイス塩基複合不斉触媒を用いた触媒的不斉シアノシリル化反応(97%,99% ee)と、ルイス酸-ブレンステッド塩基複合不斉触媒LaLitris((R)-binaphtoxide)(LLB)を用いた直接的触媒的不斉アルドール反応による触媒的分割(89% ee)を鍵行程としてそれぞれのフラグメントを合成し、鈴木クロスカップリング反応、続く山口法によるラクトン化反応によって16員環を構築し、エポシロンA、エポシロンBの触媒的不斉全合成を達成した。 Strychnosアルカロイド19,20-ジヒドロアクアマイシンの触媒的不斉全合成では、ルイス酸-ブレンステッド塩基複合不斉触媒AlLibis((R)-binaphtoxide)(ALB)を用いた触媒的不斉マイケル反応(96%,99%ee)を鍵行程として、フィッシャーインドール合成反応、DDQによる酸化的環化反応により環構築を行い、光転位反応によりメトキシカルボニル基を導入することで19,20-ジヒドロアクアマイシンの触媒的不斉全合成を達成した。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] K.Yamakoshi,S.Harwood,M.Kanai and M.Shibasaki: "Catalytic Asymmetic Addition of Diphenyphosphine Oxide to Cyclic Imines"Tetrahedron Lett. 40. 2565-2568 (1999)
[Publications] Y.Hamashima,D.Sawada,M.Kanai and M.Shibasaki: "A new Bifunctional Asymmetic Catalysis : An Efficient Catalytic Asymmetric Cyanosilylation of Aldehydes"J.Am.Chem.Soc.. 121. 2641-2642 (1999)
[Publications] N.Yoshikawa,Y.M.A.Yamada,J.Das,H.Sakai and M.Shibasaki: "Direct Catalytic Asymmetric Aldol Reaction"J.Am.Chem.Soc.. 121. 4168-4178 (1999)
[Publications] H.Sato,Y.S.Kim and M.Shibasaki: "A Catalytic Asymmetric Synthesis of a Versatile Intermediate for Phorbol Derivatives"Tetrahedron Lett.. 40. 2973-2976 (1999)
[Publications] M.Shibasaki and E.M.Vogl: "The palladium-catalysed arylation and vinylation of alkenes-enantioselective fashion"J.Organometallic Chemistry. 576. 1-15 (1999)
[Publications] M.Knai,Y.Hamashima and M.Shibasaki: "Design and Development of Lewis acid-Lewis base Bifunctional Asymmetric Catalyst"Pharmacia. 35. 690-694 (1999)
[Publications] E.Emori,T.Iieda,and M.Shibasaki: "Catalytic Kinetic Resolution Reaction of (±)-5-Methylbicyclo [3.3.0]-oct-1-ene-3,6-dione"J.Org.Chem.. 64. 5318-5320 (1999)
[Publications] S.Yamasaki,T.Iida and M.shibasaki: "Direct Catalytic Asmmetric Mannich Reaction of Unmodified Ketons : Cooperative Catalysis of an AILibis(bibapthoxide) Complex and La(OTf)_3・H_2O"Tetrahedron. 55. 8857-8867 (1999)
[Publications] E.M.Vogl,H.Groger and M.shibasaki: "Towards Perfect Asymmetic Catalysis : Addictives and Cocatalysts"Angew.Chem.Int.Ed.. 38. 1570-1577 (1999)
[Publications] F.Miyazaki,K.Ymaguchi and M.Shibasaki: "The synthesis of a new palladacycle catalyst.Development of a high performance catalyst for Heck reactions"Tetrahedron Lett.. 40. 7379-7383 (1999)
[Publications] K.Yamada,S.J.Harwood、H.groger,and M.Shibasaki: "The First Catalytic Asymmetric Nitro-Mannich-type Reaction Promoted by a New Heterobimetallic Complex"Angew.Chem.Int.Ed.. 38. 3504-3506 (1999)
[Publications] M.Shibasaki: "Multifunctional Asymmetric Catalysis"CHEMTRACTS-ORGANIC CHEMISTRY. 12. 978-988 (1999)
[Publications] M.Shibasaki: "Phorbols : Chemical Synthesis and Chemical Biology"YAKUGAKU ZASSHI. 120. 76-90 (2000)
[Publications] A.Sekina,N.Kumagai,K.Uotsu,T.Ohshima and M.Shibasaki: "An Efficient Method for the Synthesis of Versatile Intermediates Leading to 13-Deoxy- and 9,13-Dideoxyphorbols"Tetrahedron Lett.. 41. 509-513 (2000)

1999 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] K.Yamakoshi,S.Harwood,M.Kanai and M.Shibasaki: "Catalytic Asymmetic Addition of Diphenyphosphine Oxide to Cyclic Imines"Tetrahedron Lett. 40. 2565-2568 (1999)

[Publications] Y.Hamashima,D.Sawada,M.Kanai and M.Shibasaki: "A new Bifunctional Asymmetic Catalysis : An Efficient Catalytic Asymmetric Cyanosilylation of Aldehydes"J.Am.Chem.Soc.. 121. 2641-2642 (1999)

[Publications] N.Yoshikawa,Y.M.A.Yamada,J.Das,H.Sakai and M.Shibasaki: "Direct Catalytic Asymmetric Aldol Reaction"J.Am.Chem.Soc.. 121. 4168-4178 (1999)

[Publications] H.Sato,Y.S.Kim and M.Shibasaki: "A Catalytic Asymmetric Synthesis of a Versatile Intermediate for Phorbol Derivatives"Tetrahedron Lett.. 40. 2973-2976 (1999)

[Publications] M.Shibasaki and E.M.Vogl: "The palladium-catalysed arylation and vinylation of alkenes-enantioselective fashion"J.Organometallic Chemistry. 576. 1-15 (1999)

[Publications] M.Knai,Y.Hamashima and M.Shibasaki: "Design and Development of Lewis acid-Lewis base Bifunctional Asymmetric Catalyst"Pharmacia. 35. 690-694 (1999)

[Publications] E.Emori,T.Iieda,and M.Shibasaki: "Catalytic Kinetic Resolution Reaction of (±)-5-Methylbicyclo [3.3.0]-oct-1-ene-3,6-dione"J.Org.Chem.. 64. 5318-5320 (1999)

[Publications] S.Yamasaki,T.Iida and M.shibasaki: "Direct Catalytic Asmmetric Mannich Reaction of Unmodified Ketons : Cooperative Catalysis of an AILibis(bibapthoxide) Complex and La(OTf)_3・H_2O"Tetrahedron. 55. 8857-8867 (1999)

[Publications] E.M.Vogl,H.Groger and M.shibasaki: "Towards Perfect Asymmetic Catalysis : Addictives and Cocatalysts"Angew.Chem.Int.Ed.. 38. 1570-1577 (1999)

[Publications] F.Miyazaki,K.Ymaguchi and M.Shibasaki: "The synthesis of a new palladacycle catalyst.Development of a high performance catalyst for Heck reactions"Tetrahedron Lett.. 40. 7379-7383 (1999)

[Publications] K.Yamada,S.J.Harwood、H.groger,and M.Shibasaki: "The First Catalytic Asymmetric Nitro-Mannich-type Reaction Promoted by a New Heterobimetallic Complex"Angew.Chem.Int.Ed.. 38. 3504-3506 (1999)

[Publications] M.Shibasaki: "Multifunctional Asymmetric Catalysis"CHEMTRACTS-ORGANIC CHEMISTRY. 12. 978-988 (1999)

[Publications] M.Shibasaki: "Phorbols : Chemical Synthesis and Chemical Biology"YAKUGAKU ZASSHI. 120. 76-90 (2000)

[Publications] A.Sekina,N.Kumagai,K.Uotsu,T.Ohshima and M.Shibasaki: "An Efficient Method for the Synthesis of Versatile Intermediates Leading to 13-Deoxy- and 9,13-Dideoxyphorbols"Tetrahedron Lett.. 41. 509-513 (2000)

柴崎正勝東京大学, 大学院・薬学系研究科, 教授 (30112767)