Asymmetric Total Synthesis of Medium-sized Lactones Using Rapid Cyclization

• Project/Area Number: 17350023
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Organic chemistry
• Research Institution: Tokyo University of Science
• Principal Investigator: SHIINA Isamu Tokyo University of Science, 理学部, 教授 (40246690)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥10,060,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥1,260,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000); Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
• Keywords: ラクトン / 中員環 / 不斉全合成 / メリリアニン / トウシキミ / セスキテルペン / リュウマチ / ペルオキシデメチルメリリアニン / ペンタエリトリトール / ジチアンカップリング / 還元的カップリング / 5-エピメリリアニン / 三環性分子 / 7員環ラクトン / 高速縮合反応 / 不斉アルドール反応 / ヨウ化サマリウム / 分子内カップリング / ボトチノリド / 2-エピボトチノリド / 9員環ジラクトン / 立体選択的合成法 / MNBA / 置換安息香酸無水物法 / アンチマイシン / 天然薬理活性ラクトン / オクタラクチン / 中員環ラクトン / アルドール反応 / ラクトン化 / 2-メチル-6-ニトロ安息香酸無水物

Research Abstract

置換安息香酸無水物を脱水縮合剤として用いる迅速閉環反応、ならびに不斉アルドール反応を鍵工程とすることにより、9員環ラクトンであるボトシノリド類の不斉全合成を達成し、さらに8員環ラクトンであるアスタコラクチンの主骨格形成を実現した。引き続き、ボトシノリド類の構造修正体であるボトシニン酸とその類縁体の不斉全合成も完了し、イネいもち病菌に対する抗菌剤開発の端緒を切り開くことに成功した

Research Products

• [Journal Article] Chemistry and Structural Determination of Botcinolides (2009)
  • Author(s): Botcinins, and Botcinic Acids, Isamu SHIINA and Hiroki FUKUI
  • Journal Title: Chemical Communications Pages: 385-400
• [Journal Article] Total Synthesis and the Confirmation of the Revised Structures of Botcinins A and B (2009)
  • Author(s): Hiroki FUKUI, Keisuke TSUJI, Yuma UMEZAKI, andIsamu SHIINA
  • Journal Title: Heterocycles 79 Pages: 403-410
• [Journal Article] Asymmetric Total Synthesis of Botcinic Acid and Its Derivatives : Synthetic Revision ofthe Structure of Botcinolides (2008)
  • Author(s): Hiroki FUKUI, Seiichi HITOMI, Ryo-suke SUZUKI, TatsuhikoIKEDA, Yuma UMEZAKI, Keisuke TSUJI, andIsamu SHIINA
  • Journal Title: Tetrahedron Letters 49 Pages: 6514-6517
• [Journal Article] Asymmetric Total Synthesis of Botcinins C, D, and F (2008)
  • Author(s): Hiroki FUKUI and Isamu SHIINA
  • Journal Title: Organic Letters 10 Pages: 3153-3156
• [Journal Article] Total Synthesis of 2-Hydroxytetracosanolide and 2-Hydroxy-24-oxooctacosanolide Using anEffective Lactonization (2008)
  • Author(s): Isamu SHIINA, Akane SASAKI, Takaaki KIKUCHI, and Hiroki FUKUI
  • Journal Title: Chemistry-an Asian Journal 3 Pages: 462-472
• [Journal Article] Total Synthesis of 2-Hydroxytetracosanolide and 2-Hydroxy-24-oxooctacosanolide Using an Effective Lactonization (2008)
  • Author(s): Isamu SHIINA
  • Journal Title: Chemistry-an Asian Journal 2 Pages: 462-472
  • Peer Reviewed
• [Journal Article] Asymmetric Total Synthesis of Botcinins C, D, and F (2008)
  • Author(s): Hiroki FUKUI
  • Journal Title: Organic Letters 10 Pages: 3153-3156
  • Peer Reviewed
• [Journal Article] Synthesis and Pharmacological Evaluation of the Novel pseudo-Symmetrical Tamoxifen Derivatives as Anti-tumor Agents (2008)
  • Author(s): 椎名勇
  • Journal Title: Biochemical Pharmacology 75 Pages: 1014-1026
  • Peer Reviewed
• [Journal Article] Total Synthesis of 2-Hydroxytetracosanolide and 2-Hydroxy-24-oxooctacosanolide Using an Effective Lactonization (2008)
  • Author(s): 椎名勇
  • Journal Title: Chemistry-an Asian Journal 3 Pages: 462-472
  • Peer Reviewed
• [Journal Article] Synthesis of Lactones Using Substituted Benzoic Anhydride as a Coupling Reagent (2007)
  • Author(s): Isamu SHIINA, Hiroki FUKUI, and Akane SASAKI
  • Journal Title: Nature Protocols 2 Pages: 2312-2317
• [Journal Article] Total Synthesis of Natural 8- and 9- Membered Lactones : Recent Advancements inMedium-Sized Ring Formation (2007)
  • Author(s): Isamu SHIINA
  • Journal Title: Chemical Reviews 107 Pages: 239-273
• [Journal Article] Synthesis of the New pseudo-Symmetrical Tamoxifen Derivatives and Their Anti-tumor Activity (2007)
  • Author(s): 椎名勇
  • Journal Title: Bioorganic & Medicinal Chemistry Letters 17 Pages: 2421-2424
  • Peer Reviewed
• [Journal Article] Synthesis of Lactones Using Substituted Benzoic Anhydride as a Coupling Reagent (2007)
  • Author(s): 椎名勇
  • Journal Title: Nature Protocols 2 Pages: 2312-2317
  • Peer Reviewed
• [Journal Article] The First Asymmetric Esterification of Free Carboxylic Acids with Racemic Alcohols Using Benzoic Anhydrides and Tetramisole Derivatives: An Application to the Kinetic Resolution of Secondary Benzylic Alcohols (2007)
  • Author(s): 椎名勇
  • Journal Title: Tetrahedron Letters 48 Pages: 8314-8317
  • Peer Reviewed
• [Journal Article] An Expeditious Synthesis of Tamoxifen, A Representative SERM (Selective Estrogen Receptor Modulator), via the Three-Component Coupling Reaction among Aromatic Aldehyde, Cinnamyltrimethylsilane and β-Chlorophenetole (2007)
  • Author(s): 椎名勇
  • Journal Title: Bioorganic & Medicinal Chemistry 15 Pages: 7599-7617
  • Peer Reviewed
• [Journal Article] An Expeditious Synthesis of Lasofoxifene and Nafoxidine via the Novel Three-component Coupling Reaction (2007)
  • Author(s): Yoshiyuki SANO
  • Journal Title: Chemistry Letters 36 Pages: 40-41
• [Journal Article] Total Synthesis of Natural 8- and 9-Membered Lactones : Recent Advancement in Medium-sized Ring Formation (2007)
  • Author(s): Isamu SHIINA
  • Journal Title: Chemical Reviews 107 Pages: 239-273
• [Journal Article] Synthesis of the New pseudo-Symmetrical Tamoxifen Derivatives and Their Anti-tumor Activity (2007)
  • Author(s): Isamu SHIINA
  • Journal Title: Bioorganic ＆ Medicinal Chemistry Letters 17 Pages: 2421-2424
• [Journal Article] Synthesis of Lactones Using Substituted Benzoic Anhydride as a Coupling Reagent (2007)
  • Author(s): Isamu SHIINA
  • Journal Title: Nature Protocols 2(印刷中)
• [Journal Article] Stereoselective Total Synthesis of the Proposed Structure of 2-Epibotcinolide (2006)
  • Author(s): Isamu SHIINA, Yu-ji TAKASUNA, Ryo-suke SUZUKI,Hiromi OSHIUMI, Yuri KOMIYAMA, SeiichiHITOMI, and Hiroki FUKUI
  • Journal Title: Organic Letters 8 Pages: 5279-5282
• [Journal Article] The First Total Synthesis of(-)and(+)-2-Hydroxy-24-oxooctacosanolide Using anEffective Lactonization (2006)
  • Author(s): Isamu SHIINA, Takaaki KIKUCHI, and Akane SASAKI
  • Journal Title: Organic Letters 8 Pages: 4955-4958
• [Journal Article] Synthesis of (9E)-Isoambrettolide, a Macrocyclic Musk Compound, Using the Effective Lactonization Promoted by SymmetricBenzoic Anhydrides with Basic Catalysts (2006)
  • Author(s): Isamu SHIINA and Minako HASHIZUME
  • Journal Title: Tetrahedron 62 Pages: 7934-7939
• [Journal Article] Short-step Synthesis of Droloxifene via the Three-component Coupling Reaction among Aromatic Aldehyde, Cinnamyltrimethylsilane, and β-Chlorophenetole (2006)
  • Author(s): Yoshiyuki SANO
  • Journal Title: Tetrahedron Letters 47 Pages: 1631-1635
• [Journal Article] Computational Study on the Reaction Mechanism of the Key Thermal [4+4] Cycloaddition Reaction in the Biosynthesis of Epoxytwinol A (2006)
  • Author(s): Isamu SHIINA
  • Journal Title: Organic Letters 8 Pages: 1041-1044
• [Journal Article] Synthesis of (9E)-Isoambrettolide, a Macrocyclic Musk Compound, Using the Effective Lactonization Promoted by Symmetric Benzoic Anhydrides with Basic Catalysts (2006)
  • Author(s): Isamu SHIINA
  • Journal Title: Tetrahedron 62 Pages: 7934-7939
• [Journal Article] 1-Methoxy-2-methylseleno-1-(trimethylsiloxy)propene (2006)
  • Author(s): Isamu SHIINA
  • Journal Title: Electronic Encyclopedia of Reagents for Organic Synthesis 8 Pages: 1-12
• [Journal Article] Asymmetric Synthesis of 8 or 9-Membered Ring Natural Compounds Using a Rapid Lactonization to Form a Medium-sized Framework (2006)
  • Author(s): Isamu SHIINA
  • Journal Title: Journal of the Mexican Chemical Society 50 Pages: 262-262
• [Journal Article] 置換安息香酸無水物を用いる実用的縮合反応 (2006)
  • Author(s): 椎名 勇
  • Journal Title: ケミカルエンジニアリング 51 Pages: 702-706
• [Journal Article] The First Total Synthesis of (-) and (+)-2-Hydroxy-24-oxooctacosanolide Using an Effective Lactonization (2006)
  • Author(s): Isamu SHIINA
  • Journal Title: Organic Letters 8 Pages: 4955-4958
• [Journal Article] Stereoselective Total Synthesis of the Proposed Structure of 2-Epibotcinolide (2006)
  • Author(s): Isamu SHIINA
  • Journal Title: Organic Letters 8 Pages: 5279-5282
• [Journal Article] Short-step Synthesis of Droloxifene via the Three-component Coupling Reaction among Aromatic Aldehyde, Cinnamyltrimethylsilane, and β-Chlorophenetole (2006)
  • Author(s): Yoshiyuki SANO
  • Journal Title: Tetrahedron Letters 47(印刷中)
• [Journal Article] Computational Study on the Reaction Mechanism of the Key Thermal [4+4] Cycloaddition Reaction in the Biosynthesis of Epoxytwinol A (2006)
  • Author(s): Isamu SHIINA
  • Journal Title: Organic Letters 8(印刷中)
• [Journal Article] 置換安息香酸無水物を用いる大員環および中員環ラクトン類の高速合成反応の開発 (2005)
  • Author(s): 椎名 勇
  • Journal Title: 有機合成化学協会誌 63 Pages: 2-17
  • NAID: 10014102095
• [Journal Article] Total Synthesis of Buergerinin F via Effective Construction of the Asymmetric Quaternary Carbons Using Enantioselective Aldol Reaction (2005)
  • Author(s): Isamu SHIINA
  • Journal Title: Chemical Communications 2005 Pages: 4062-4064
• [Journal Article] Enantioselective Synthesis of the Optically Active α-Methylene-β-hydroxy Esters, Equivalent Compounds to Morita-Baylis-Hillman Adducts, Using Successive Asymmetric Aldol Reaction and Oxidative Deselenization (2005)
  • Author(s): Isamu SHIINA
  • Journal Title: Journal of Organic Chemistry 70 Pages: 8103-8106
• [Journal Article] Enantioselective Total Synthesis of Octalactin A Using Asymmetric Aldol Reactions and a Rapid Lactonization to form a Medium-sized Ring (2005)
  • Author(s): Isamu SHIINA
  • Journal Title: Chemistry-a European Journal 11 Pages: 6601-6608
• [Journal Article] The Direct, Enantioselective, One-pot, Three-component, Cross-Mannich Reaction of Aldehydes : The Reason for the Higher Reactivity of Aldimine Versus Aldehyde in Proline-Mediated Mannich and Aldol Reactions (2005)
  • Author(s): Yujiro HAYASHI
  • Journal Title: Advanced Synthesis & Catalysis 347 Pages: 1595-1604
• [Journal Article] Enantio- and Diastereo-selective Total Synthesis of EI-1941-1,-2 and -3, Inhibitors of Interleukin-1β Converting Enzyme and Biological Properties of Their Derivatives (2005)
  • Author(s): Mitsuru SHOJI
  • Journal Title: Journal of Organic Chemistry 70 Pages: 9905-9915
• [Journal Article] Chemistry and Structural Determination of Botcinolides, Botcinins, and Botcinic Acids
  • Author(s): Isamu SHIINA
  • Journal Title: Chemical Communications 2009 Pages: 385-400
  • Peer Reviewed
• [Presentation] ボトシニンAおよびBの不斉全合成 (2009)
  • Author(s): 椎名勇(他3名)
  • Organizer: 日本化学会第89春季年会
  • Year and Date: 2009-03-30
• [Presentation] ボトシニンD類縁体の合成ならびに抗菌活性 (2009)
  • Author(s): 椎名勇(他2名)
  • Organizer: 日本化学会第89春季年会
  • Year and Date: 2009-03-30
• [Presentation] ペルオキシボトシニンDの不斉全合成 (2009)
  • Author(s): 椎名勇(他2名)
  • Organizer: 日本化学会第89春季年会
  • Year and Date: 2009-03-30
• [Presentation] アスタコラクチンの全合成研究 (2009)
  • Author(s): 椎名勇(他2名)
  • Organizer: 日本化学会第89春季年会
  • Year and Date: 2009-03-28
• [Presentation] 天然8員環状化合物アスタコラクチンの合成研究 (2008)
  • Author(s): 椎名勇(他1名)
  • Organizer: 日本化学会第88春季年会
  • Year and Date: 2008-03-29
• [Presentation] 2-エピボトシノリドおよびボトシニンC, D, Fの不斉全合成 (2008)
  • Author(s): 椎名勇(他7名)
  • Organizer: 日本化学会第88春季年会
  • Year and Date: 2008-03-27
• [Presentation] ボトシニン酸およびボトシニンEの全合成研究 (2008)
  • Author(s): 椎名勇(他2名)
  • Organizer: 日本化学会第88春季年会
  • Year and Date: 2008-03-27
• [Presentation] ペルオキシボトシニン類の不斉合成研究 (2008)
  • Author(s): 椎名勇(他2名)
  • Organizer: 日本化学会第88春季年会
  • Year and Date: 2008-03-27
• [Presentation] 2-エピボトチノリド提案構造の不斉合成 (2007)
  • Author(s): 椎名勇(他4名)
  • Organizer: 日本化学会第87春季年会
  • Year and Date: 2007-03-25
• [Presentation] ボトチノリド類修正構造の不斉合成研究 (2007)
  • Author(s): 椎名勇(他4名)
  • Organizer: 日本化学会第87春季年会
  • Year and Date: 2007-03-25
• [Presentation] MNBAを用いた高速ラクトン形成法によるボトチノリド類の合成研究 (2006)
  • Author(s): 椎名勇(他4名)
  • Organizer: 日本化学会第86春季年会
  • Year and Date: 2006-03-30
• [Presentation] ボトチノリド類の側鎖の不斉合成ならびに9員環ラクトン部とのカップリング反応 (2006)
  • Author(s): 椎名勇(他3名)
  • Organizer: 日本化学会第86春季年会
  • Year and Date: 2006-03-30
• [Book] New Acid Catalysis for Modern Organic Chemistry(2) (2008)
  • Author(s): Isamu SHIINA and Hiroki HUKUI
  • Publisher: Wiley-VCH
• [Book] Electronic Encyclopedia of Reagents for Organic Synthesis(10) (2008)
  • Author(s): Isamu SHIINA
  • Publisher: 2-Methyl-6-nitrobenzoic Anhydride (MNBA)
• [Book] New Acid Catalysis for Modern Organic Chemistry (2008)
  • Author(s): Isamu SHIINA
  • Publisher: Wiley-VCH
• [Remarks] Banyu Young Chemist Award 2006((財)万有生命科学振興国際交流財団)
• [Remarks]
  • URL: http://www.sut.ac.jp/fac/teacher/index.php?A06637
• [Remarks]
  • URL: http://www.sut.ac.jp/fac/teacher/index.php?A06637
• [Patent(Industrial Property Rights)] 特許 (2006)
  • Inventor(s): 椎名勇, 佐野義之
  • Industrial Property Rights Holder: 東京理科大学
  • Industrial Property Number: 2006-018079
  • Filing Date: 2006-01-26
• [Patent(Industrial Property Rights)] 特許 (2005)
  • Inventor(s): 椎名 勇
  • Industrial Property Rights Holder: 東京理科大学
  • Industrial Property Number: 2005-061558
  • Filing Date: 2005-03-04