1993 Fiscal Year Annual Research Report

不斉空間の構築

Research Project

Project/Area Number	05234104
Research Institution	The University of Tokyo
Principal Investigator	古賀憲司東京大学, 薬学部, 教授 (10012600)
Co-Investigator(Kenkyū-buntansha)	板井昭子東京大学, 薬学部, 客員助教授 (60012647) 中村栄一東京工業大学, 理学部, 助教授 (00134809) 富岡清大阪大学, 産業科学研究所, 教授 (50114575) 向山光昭東京理科大学, 理学部, 教授 (60016003) 富士薫京都大学, 化学研究所, 教授 (20027056)
Keywords	不斉空間 / キラルリチウムアミド / 不斉記憶 / 立体選択的グリコシル化反応 / 有機リチウム / 立体選択的アリル化 / 生体高分子
Research Abstract	1 効率的な不斉空間を構築するキラルリチウムアミドを設計して、環状アキラルケトンの不斉脱プロトン化反応、不斉アルキル化反応、不斉プロトン化反応を実現、前二者の反応については触媒化に成功した。キラルリチウムアミドの溶液構造を^6Liおよび^<15>NNMR、結晶構造をX線結晶構造解析により解明し、実際の反応との相関性を明らかにした。 2 不斉記憶の概念に基づけば、光学活性なα-アミノ酸誘導体から生成するエノレートもキラリテイーを持てると期待できる。そこでフェニルアラニン誘導体を塩基(LiTMP)処理して生成するエノレートとハロゲン化アルキルとの反応を行ったところ、最高88%eeで不斉アルキル化反応が進行した。 3 糖質を不斉源として有機合成反応に利用することを考え、糖質誘導体、とくに糖質の1位のアノメリック炭素に由来する二つのジアステレオマーを効率良く合成する手法の開発を目標に研究を行い、種々の高立体選択的グリコシル化反応を見い出すことができた。 4 反応性に富む有機リチウムを炭素求核剤として組み込み可能な不斉触媒反応系の構築を目指して検討を進めた。その結果、立体化学と反応性の制御を同時に可能とするキラル配位子としてヒドロベンゾインのジメチルエーテルやキラルアミノエーテルが有機リチウムのイミンへの付加反応を制御して、最高90%eeのアミンの不斉合成を達成することがわかった。さらに、触媒回転も可能とすることがわかった。 5 合理的設計に基づいた不斉反応の開発:有機金属化合物の付加反応を中心課題として取り上げ、立体選択的アリル化反応の開発とその選択性の検討、オレフィンのアリルメタル化反応の立体化学制御、およびカルボニル化合物への有機金属化合物の付加の遷移状態の理論計算を行った。 6 生体高分子のつくる不斉空間に対して、特異的に結合する新規リガンドを設計するための方法論を開発し、その有効性を示す。また、それらの方法論を利用した応用研究を行う。

Research Products
(21 results)

All Other

All Publications (21 results)

[Publications] Tatsuro Yasukata: "Enontioselective Protonation of Achiral Lithium Enolates Using a Chiral Amine in the Presence of Lithium Bromidc" Tetrahedron:Asymmetry. 4. 35-38 (1993)
[Publications] Yoshihiro Hasegawa: "Control of Diastereoselectivity in the Alkylation of chiral Lithium Enolates Mediated by a Chiral Secondary Amime Ligand" Tetrahedron Letters. 34. 1963-1966 (1993)
[Publications] Kazumasa Aoki: "Reinvestigation on the Optical Purities of Optically Active Trimethylsilyl Enol Ethers of 4-Substitnted Cyclohexanones" Chem.Pharm.Bull.41. 994-996 (1993)
[Publications] Masao Sobukawa: "Determination of the Protons Eliminated in the Regioselective Deprotonation of Some Optically Active 3-Keto Steroids" Tetrahedron Letters. 34. 1501-1504 (1993)
[Publications] Kazumasa Aoki: "Enantioselective Deprotonation of 4-Substituted Cyclohexanones by Chiral Lithium Amides Having a Fluorine-containing Group" Tetrahedron Letters. 34. 1505-1508 (1993)
[Publications] Kaoru Fuji: "Asymmetric Creation of Ouaternary Carbon Centers" Chem.Rev.93. 2037-2066 (1993)
[Publications] Kiyoshi Tanaka: "Differentiation of Enantiotopic Carbonyl Groups by Honnor-Wadsworth-Emmous Reaction" Tetrahedron Letters. 34. 4071-4074 (1993)
[Publications] Takeo Kawabata: "An Enantiodivengent Synthesis of threo-β-Amino Alcohols:Preparation of Key Intermediates for Bestatin and the Related Peptides" Tetrahedron Letters. 34. 5127-5130 (1993)
[Publications] Koki Matsubara: "Stereoselective Synthesis of 0-(2-Azido-2-deoxy-α-D-galactopyranosyl)-L-segine and-L-threonine Derivatives by Using the Catalytic Ameunts of Active Acidic species." Chemistry Letters. 581-584 (1993)
[Publications] Koki Matsubara: "Catalytic Stereoselective Synthesis of 2-Amino-2-deoxy-α-D-glucopyrarosides and Galactopyranosides" Chemistry Letters. 2145-2148 (1993)
[Publications] Koki Matsubara: "High-yiddiry Catalytie Synthesis of Glycosyl Azidesfrom Peracylated Sugars" Chemistry Letters. 247-250 (1994)
[Publications] Kiyoshi Tomioka: "Asymmetrie Addition of Aryllithiuns to Naphthalere BHA-esters Catalyzed by a chiral Ligand" Tetrahedron Letters. 34. 681-682 (1993)
[Publications] Motomu Kanai: "Solvent Effect and NMR Behaviorer in a Chiral Amidophosphine Mediated Reaction of Organocuprate and Chalcone" J.Chem.Soc.,Chem.Commun.1248-1249 (1993)
[Publications] Kiyoshi Tomioka: "Steric Tuning in Chiral Ligand-Cotalyzed Enantioselective Alkylation of Imines" Tetrahedron:Asymmetry. 4. 1603-1606 (1993)
[Publications] K.Kubota: "Ligand Control in the Stereoselective Allylzincation of Cydopropenes" J.Am.Chem.Soc.115. 5867-5868 (1993)
[Publications] M.Arai: "1.2-Asymmetric Induction in the S_N2^1-Allylation of Organocopper and Organozinc Regents" J.Org.Chem.58. 5121-5129 (1993)
[Publications] M.Nakamura: "Theoretical Studies on the Reaction of Solv Methyllithium Open Dimer with Aldehyde" J.Am.Chem.Soc.115. 11016-11017 (1993)
[Publications] M.Yamada: "Development of An Efficient Automated Docking Method" Chem.Pharm.Bull.41. 1200-1202 (1993)
[Publications] Y.Nishibata: "Confirmation of Usefulness of a Structure Construetion Program Based on Three-dimensional Receptor Stweture for Rational Lead Generation" J.Med.Chem.36. 2921-2928 (1993)
[Publications] M.Ohno: "Designed Molecules.Reproducing the Active Conformation of Teleocidins" Tetrahedron Letters. 34. 8119-8122 (1993)
[Publications] A.Itai: "3D-QSAR in Drug Design,Theory,Methods and Applications" ESCOM Science Publishers B.V.,Leiden,Netherland., (1993)

1993 Fiscal Year Annual Research Report

不斉空間の構築

Principal Investigator

古賀 憲司 東京大学, 薬学部, 教授 (10012600)

Research Products

[Publications] Tatsuro Yasukata: "Enontioselective Protonation of Achiral Lithium Enolates Using a Chiral Amine in the Presence of Lithium Bromidc" Tetrahedron:Asymmetry. 4. 35-38 (1993)

[Publications] Yoshihiro Hasegawa: "Control of Diastereoselectivity in the Alkylation of chiral Lithium Enolates Mediated by a Chiral Secondary Amime Ligand" Tetrahedron Letters. 34. 1963-1966 (1993)

[Publications] Kazumasa Aoki: "Reinvestigation on the Optical Purities of Optically Active Trimethylsilyl Enol Ethers of 4-Substitnted Cyclohexanones" Chem.Pharm.Bull.41. 994-996 (1993)

[Publications] Masao Sobukawa: "Determination of the Protons Eliminated in the Regioselective Deprotonation of Some Optically Active 3-Keto Steroids" Tetrahedron Letters. 34. 1501-1504 (1993)

[Publications] Kazumasa Aoki: "Enantioselective Deprotonation of 4-Substituted Cyclohexanones by Chiral Lithium Amides Having a Fluorine-containing Group" Tetrahedron Letters. 34. 1505-1508 (1993)

[Publications] Kaoru Fuji: "Asymmetric Creation of Ouaternary Carbon Centers" Chem.Rev.93. 2037-2066 (1993)

[Publications] Kiyoshi Tanaka: "Differentiation of Enantiotopic Carbonyl Groups by Honnor-Wadsworth-Emmous Reaction" Tetrahedron Letters. 34. 4071-4074 (1993)

[Publications] Takeo Kawabata: "An Enantiodivengent Synthesis of threo-β-Amino Alcohols:Preparation of Key Intermediates for Bestatin and the Related Peptides" Tetrahedron Letters. 34. 5127-5130 (1993)

[Publications] Koki Matsubara: "Stereoselective Synthesis of 0-(2-Azido-2-deoxy-α-D-galactopyranosyl)-L-segine and-L-threonine Derivatives by Using the Catalytic Ameunts of Active Acidic species." Chemistry Letters. 581-584 (1993)

[Publications] Koki Matsubara: "Catalytic Stereoselective Synthesis of 2-Amino-2-deoxy-α-D-glucopyrarosides and Galactopyranosides" Chemistry Letters. 2145-2148 (1993)

[Publications] Koki Matsubara: "High-yiddiry Catalytie Synthesis of Glycosyl Azidesfrom Peracylated Sugars" Chemistry Letters. 247-250 (1994)

[Publications] Kiyoshi Tomioka: "Asymmetrie Addition of Aryllithiuns to Naphthalere BHA-esters Catalyzed by a chiral Ligand" Tetrahedron Letters. 34. 681-682 (1993)

[Publications] Motomu Kanai: "Solvent Effect and NMR Behaviorer in a Chiral Amidophosphine Mediated Reaction of Organocuprate and Chalcone" J.Chem.Soc.,Chem.Commun.1248-1249 (1993)

[Publications] Kiyoshi Tomioka: "Steric Tuning in Chiral Ligand-Cotalyzed Enantioselective Alkylation of Imines" Tetrahedron:Asymmetry. 4. 1603-1606 (1993)

[Publications] K.Kubota: "Ligand Control in the Stereoselective Allylzincation of Cydopropenes" J.Am.Chem.Soc.115. 5867-5868 (1993)

[Publications] M.Arai: "1.2-Asymmetric Induction in the S_N2^1-Allylation of Organocopper and Organozinc Regents" J.Org.Chem.58. 5121-5129 (1993)

[Publications] M.Nakamura: "Theoretical Studies on the Reaction of Solv Methyllithium Open Dimer with Aldehyde" J.Am.Chem.Soc.115. 11016-11017 (1993)

[Publications] M.Yamada: "Development of An Efficient Automated Docking Method" Chem.Pharm.Bull.41. 1200-1202 (1993)

[Publications] Y.Nishibata: "Confirmation of Usefulness of a Structure Construetion Program Based on Three-dimensional Receptor Stweture for Rational Lead Generation" J.Med.Chem.36. 2921-2928 (1993)

[Publications] M.Ohno: "Designed Molecules.Reproducing the Active Conformation of Teleocidins" Tetrahedron Letters. 34. 8119-8122 (1993)

[Publications] A.Itai: "3D-QSAR in Drug Design,Theory,Methods and Applications" ESCOM Science Publishers B.V.,Leiden,Netherland., (1993)

古賀憲司東京大学, 薬学部, 教授 (10012600)