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Masanori Nagatomo

Faculty of Pharmaceutical Sciences　Molecular Pharmaceutical Sciences　Chemistry and Medicinal ChemistryProfessor
Institute for Academic InnovationProfessor

2007年 東京理科大学 理学部第一部 応用化学科卒業（中田 忠 教授）
2009年 東京理科大学 大学院理学研究科 化学専攻修士課程修了（中田 忠 教授）
2010年 日本学術振興会特別研究員 (DC2)
2012年 東京大学 大学院薬学系研究科 統合薬学専攻 博士後期課程修了 [博士(薬学)]（井上 将行 教授）
2012年 東京大学 大学院薬学系研究科 助教
2012年 The Scripps Research Institute(TSRI)客員研究員（Prof. P. S. Baran）
2018年 東京大学 大学院薬学系研究科 講師
2018年～ 天然物化学談話会 世話人（2024年～同世話人代表）
2021年 東京大学卓越研究員
2023年 現職

Researcher basic information

■ Nickname etc.
  • Masanori Nagatomo
■ Degree
  • Ph.D., The University of Tokyo, Mar. 2012
■ URL
researchmap URLホームページURL■ Various IDs
Researcher number
  • 70634161
ORCID IDResearcher ID
  • HGD-2896-2022
J-Global ID■ Research Keywords and Fields
Research Keyword
  • Organic Synthetic Chemistry
  • Natural Product Synthesis
  • Taotal Synthesis
  • Photochemistry
  • Computational Chemistry
Research Field
  • Life Science, Bioorganic chemistry
  • Nanotechnology/Materials, Structural organic chemistry and physical organic chemistry
  • Nanotechnology/Materials, Synthetic organic chemistry, Organic Chemistry
  • Life Science, Pharmaceutical chemistry and drug development sciences
■ Educational Organization

Career

■ Career
Career
  • Nov. 2023 - Present
    Hokkaido University, Faculty of Pharmaceutical Sciences, Professor
  • Oct. 2021 - Oct. 2023
    The University of Tokyo, Excellent Young Researcher, Japan
  • Nov. 2018 - Oct. 2023
    The University of Tokyo, Graduate School of Pharmaceutical Sciences, Lecturer, Japan
  • Apr. 2012 - Oct. 2018
    The University of Tokyo, Graduate School of Pharmaceutical Sciences, Assistant Professor, Japan
  • Jul. 2012 - Aug. 2012
    The Scripps Research Institute, San Diego, California, Research Fellow, United States
  • Apr. 2010 - Mar. 2012
    Japan Society for the Promotion of Science, JSPS research fellow DC2, Japan
Educational Background
  • Apr. 2009 - Mar. 2012, The University of Tokyo, Graduate School of Pharmaceutical Sciences, Department of Integrated Pharmaceutical Sciences, Doctoral Program, Japan
  • Apr. 2007 - Mar. 2009, Tokyo University of Science, Graduate School of Science, Department of Chemistry, Master's Program, Japan
  • Apr. 2003 - Mar. 2007, Tokyo University of Science, Faculty of Science, Division 1, Department of Applied Chemistry, Japan
  • Apr. 1999 - Mar. 2002, Miyazaki Prefectural Miyazaki Nishi High School, Science and Mathematics Course, Japan
Committee Memberships
  • Apr. 2018 - Present
    Colloquium of natural product chemistry, manager, Society
  • Apr. 2018 - Present
    天然物化学談話会, 世話人, Society

Research activity information

■ Awards
  • Apr. 2025, UBE Foundation for the Promotion of Science, UBE Foundation for the Promotion of Science Academic Encouragement Award 2025
    HIV/AIDSの根治を志向したインゲナンエステル類の網羅的全合成と活性評価
    Masanori Nagatomo
  • Apr. 2024, Nagase Science and Technology Foundation, Nagase Foundation Award 2024
  • Mar. 2023, The Chemical Society of Japan, 37th Young Scholar Lecture Award
    Unified Total Synthesis of Daphnane, Tigliane, and Rhamnopholane Diterpenoids
    Masanori Nagatomo, 37204986;36811303
  • Dec. 2021, The Society of Synthetic Organic Chemistry, Japan, Daiichi Sankyo Research Proposal Award
    「逆」生合成経路に基づく稀少海洋産ノルジテルペン類の網羅的全合成戦略の確立
    Masanori Nagatomo
  • Oct. 2021, The University of Tokyo, The University of Tokyo Excellent Young Researcher
    Simplification of the Synthesis of Densely Oxygenated Bioactive Natural Products Based on Radical Synthetic Strategies
    Masanori Nagatomo
  • Dec. 2019, MSD Life Science Foundation, Public Interest Incorporated Foundation, Chemist Award BCA 2019
    Development of novel C-C bond formation reactions utilizing α-alkoxy and α-amino carbon radical and application to the total synthesis of densely oxygenated natural products
    Nagatomo Masanori
  • Jan. 2019, Thieme Publishing Group, The Thieme Chemistry Journals Award 2019
    Nagatomo Masanori
  • Mar. 2018, The pharmaceutical society of Japan, The Pharmaceutical Society of Japan Award for Young Scientists '18
    Development of synthetic strategies for densely oxygenated natural product
    Nagatomo Masanori
  • Jul. 2017, Colloquium of natural product chemistry, Young Scientist’s Research Award in Natural Product Chemistry
    Development of synthetic strategies for densely functionalized natural product
    Nagatomo Masanori
  • Dec. 2010, Pacifichem 2010, Student Poster Competition Award
    Synthetic Study of Ryanodine
    Nagatomo Masanori
■ Papers
■ Other Activities and Achievements
■ Books and other publications
  • 〔Major achievements〕Exploration of the Unified Total Synthetic Strategies—Unraveling and Assembling Privileged Structures
    Masanori Nagatomo, Chemistry & Chemical Industry
    The Chemical Society of Japan, Aug. 2023, 2, 584-585, Japanese, Textbook, [Peer-reviewed], [Single work]
  • 〔Major achievements〕Total Syntheses of Densely Oxygenated Natural Products by Radical-Based Decarbonylative Convergent Assembly
    Masanori Nagatomo, New Tide of Natural Product Chemistry
    Springer, Jul. 2023, 9789819917136, 377, 259-273, English, Scholarly book, 36811303;37204986, [Peer-reviewed], [Single work]
  • 〔主要な業績〕抗がん剤タキソールの全合成――ラジカル反応を活用した新しい合成戦略とその展開
    長友優典; 今村祐亮; 井上将行, 月刊化学
    化学同人, Jul. 2023, 36811303;37204986, [Joint work]
  • α-Arylation of Cyclopentanones by Palladium/Enamine Cooperative Catalysis
    Submitted by; Yibin Xue; Arjuna Parsad; Guangbin Dong; Checked by; Jaejoong Han; Masanori Nagatomo; Masayuki Inoue
    Organic Syntheses, Inc., Mar. 2023, [Joint work]
  • Stereoselective [2+2] Cycloadditions: Synthesis ofa Tri-O-Bn-D-Glucal-derived β-Lactam
    Submitted by; Maria Varghese; Hannah E. Caputo; Ruiqing Xiao; Anant Balijepalli; Aladin Hamoud; Mark W. Grinstaff; Checked by; Kyohei Oga; Masanori Nagatomo; Masayuki Inoue
    Organic Syntheses, Inc., Dec. 2021, [Joint work]
  • Preparation of 1H-Indazole-3-carbonitrile
    Submitted by; Yonggang Chen; Qinghao Chen; Lushi Tan; Lu Chen; Xiaowei Wang; Checked by; Yuma Komori; Masanori Nagatomo; Masayuki Inoue
    Organic Syntheses, Inc., 16 Oct. 2020, [Joint work]
  • Preparation of (-)-Levoglucosenone from Cellulose Using Sulfuric Acid in Polyethylene Glycol
    Submitted by J. Klepp, W. Dillon, Y. Lin, P. Feng, B. W. Greatrex, Checked by Y. Imamura, M. Nagatomo, M. Inoue
    Organic Syntheses, Inc., 02 Mar. 2020, [Joint work]
  • Nickel-Catalyzed Cross-Coupling of 2-Methoxynaphthalene with Methyl 4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzoate
    Submitted by; Yuki Kawashima; Takayuki Furukawa; Naoto Chatani; Mamoru Tobisu Checked by; Takumi Fukuda; Masanori Nagatomo; Masayuki Inoue
    Organic Syntheses, Inc., 04 Feb. 2019, 36-52, English, [Joint work]
  • 〔主要な業績〕天然有機化合物の全合成 : 独創的なものづくりの反応と戦略
    日本化学会, リアノダンジテルペンの統一的全合成
    化学同人, Mar. 2018, 9784759813876, v, 193p, 図版 [4] p, Japanese, [Joint work]
  • 〔Major achievements〕Development of synthetic strategies for densely oxygenated natural product
    Nagatomo Masanori
    Yakujinippo, Mar. 2018, Japanese, Scholarly book, [Single work]
  • 〔Major achievements〕Convergent synthetic strategies of the highly oxygenated natural products based on radical reactions
    Inoue Masayuki; Nagatomo Masanori; Urabe Daisuke
    Farumashia, Sep. 2017, 5, Japanese, Scholarly book, [Joint work]
  • Unified total synthesis of ryanodine and its congeners
    Nagatomo Masanori; Inoue Masayuki
    KAGAKU, Apr. 2016, 2, Japanese, Scholarly book, http://www.f.u-tokyo.ac.jp/~inoue/assets/pdf/kagaku2016.pdf, [Joint work]
  • Pentafluorophenyl Isocyanate
    T. Hoshikawa; M. Nagatomo; M. Inoue
    e-EROS, Sep. 2013, 047084289X, English, Dictionary or encycropedia, [Joint work]
■ Syllabus
  • 卒業研究準備実習Ⅰ, 2024年, 学士課程, 薬学部
  • 創薬化学特論, 2024年, 修士課程, 生命科学院
  • 卒業研究準備実習Ⅱ, 2024年, 学士課程, 薬学部
  • 実践有機合成化学特論, 2024年, 修士課程, 生命科学院
  • 薬学論文講読演習Ⅰ, 2024年, 学士課程, 薬学部
  • 有機化学Ⅱ, 2024年, 学士課程, 薬学部
  • 薬学論文講読演習Ⅱ, 2024年, 学士課程, 薬学部
  • 有機合成化学演習Ⅱ, 2024年, 学士課程, 薬学部
  • 薬学論文講読演習Ⅲ, 2024年, 学士課程, 薬学部
  • 薬学総合演習, 2024年, 学士課程, 薬学部
  • 薬学卒業研究, 2024年, 学士課程, 薬学部
  • 薬科学演習, 2024年, 学士課程, 薬学部
  • 薬科学論文講読演習, 2024年, 学士課程, 薬学部
  • 薬科学卒業研究, 2024年, 学士課程, 薬学部
  • 生命科学研究, 2024年, 修士課程, 生命科学院
  • 生命科学実習, 2024年, 修士課程, 生命科学院
  • 生命科学論文講読Ⅰ, 2024年, 修士課程, 生命科学院
  • 生命科学論文講読Ⅱ, 2024年, 修士課程, 生命科学院
  • 生命科学特別研究, 2024年, 博士後期課程, 生命科学院
  • 生命科学文献講読, 2024年, 博士後期課程, 生命科学院
  • 臨床薬学論文講読Ⅰ, 2024年, 博士後期課程, 生命科学院
■ Affiliated academic society
  • THE SOCIETY OF SYNTHETIC ORGANIC CHEMISTRY, JAPAN
  • THE CHEMICAL SOCIETY OF JAPAN
  • THE PHARMACEUTICAL SOCIETY OF JAPAN
  • Japan Society for Bioscience, Biotechnology, and Agrochemistry
  • The Japanese Society of Pharmacognosy
■ Research Themes
  • 天然物主導型電位依存性ナトリウムチャネル制御因子の創製
    科学研究費助成事業
    Apr. 2025 - Mar. 2028
    長友 優典
    日本学術振興会, 基盤研究(B), 北海道大学, Principal investigator, 25K02380
  • Unified total synthesis of the unexplored densely oxygenated daphnane diterpenes for drug lead discovery
    Grants-in-Aid for Scientific Research
    01 Apr. 2022 - 31 Mar. 2025
    長友 優典
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), The University of Tokyo, 22K06521
  • Development of Innovative Photoreactions with MI Implementation: Presentation and Realization of an Unexplored Retrosynthetic Strategy for Highly Oxidized Natural Products
    Grants-in-Aid for Scientific Research Grant-in-Aid for Transformative Research Areas (A)
    Jun. 2022 - Mar. 2024
    Masanori Nagatomo
    Japan Society for the Promotion of Science, Grant-in-Aid for Transformative Research Areas (A), The University of Tokyo, Principal investigator, 22H05341
  • Toward the Total Synthesis of Trigocherrins
    2022 Research Grants
    Oct. 2022 - Sep. 2023
    Masanori Nagatomo
    Kowa Life Science Foundation, Research Topic C "Research on Countermeasures against Infectious Diseases that Threaten Humankind", Graduate School of Pharmaceutical Sciences, The University of Tokyo, Principal investigator
  • The University of Tokyo Excellent Young Researcher Program
    Apr. 2021 - Mar. 2023
    Masanori Nagatomo
    The University of Tokyo, Simplification of the Synthesis of Densely Oxygenated Bioactive Natural Products Based on Radical Synthetic Strategies, The University of Tokyo, Principal investigator
  • Application of hybrid catalysis-mediated multi-component coupling reactions for efficient construction of densely functionalized natural products
    Grants-in-Aid for Scientific Research
    Jun. 2017 - Mar. 2022
    Inoue Masayuki
    We utilized multicomponent coupling reactions to assemble densely functionalized natural products. We developed hybrid catalysis-mediated cross-coupling, two- and three-component radical reactions, radical dimerization, photoredox-catalyzed radical cyclization, and two-component TiO2-mediated radical reactions to streamline the convergent syntheses of highly complex structures. These new strategies and tactics enabled us to minimize the functional group transformations, thereby simplifying the synthetic routes to the target structures. Consequently, we achieved the concise and efficient total syntheses of a diverse collection of densely functionalized natural products, including anticancer agent taxol. Since synthetic organic chemistry is a key science and technology for the development of new pharmaceuticals, the achievements of this project will have a significant impact on chemistry, biology, and pharmaceutical sciences.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), The University of Tokyo, 17H06452
  • Expanding the medicinally relevant chemical space with architecturally complex natural products and their synthetic analogues
    Grants-in-Aid for Scientific Research
    May 2017 - Mar. 2022
    Inoue Masayuki
    Architecturally complex natural products with molecular weight of over 500 often exhibit potent bioactivities, and represent privileged structures for the development of pharmaceuticals. We achieved many total syntheses of the complex terpenes, nucleosides, and peptides. The developed strategies and tactics significantly simplified the synthetic routes to the natural products, thereby facilitating their practical preparations. Furthermore, a medicinally relevant chemical space was expanded by the preparation of numerous natural product analogues, leading to the discovery of new artificial analogues with higher or disparate bioactivities. Structure-activity relationship studies of these analogues enabled us to determine biologically significant structural features and to elucidate their mode of actions. The thus-obtained results together will serve as valuable information for the synthesis and design of novel molecules with more potent and selective biological activities.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (S), The University of Tokyo, 17H06110
  • Development of strategy toward the unified total synthesis of natural and artificial daphnan/tigrian diterpenoids and discovery of new functional molecules
    Grant-in-Aid for Young Scientists
    Apr. 2019 - Mar. 2021
    Nagatomo Masanori
    Rhamnofolane, tigliane, and daphnane diterpenoids are known to exhibit a wide range of important biological activities depending on their substituent patterns and have great potential for the discovery of new drugs. However, it is extremely difficult to utilize these highly oxidized middle-molecular diterpenes as lead compounds for new drugs due to the complexity of their chemical structures. In this study, we attempted to solve this problem, which is of high social importance. As a result, we established a method for the construction of the tricyclic synthetic intermediate with the common carbon skeleton. We achieved the total synthesis of three natural products, resiniferatoxin, prostratin, and crotophorbolone from the common intermediates, all in about 20 steps from the starting materials.
    Japan Society for the Promotion of Science, Grant-in-Aid for Early-Career Scientists, The University of Tokyo, Principal investigator, Competitive research funding, 19K15554
  • Total synthesis and advanced reaction integration of the densely functionalized medium molecular terpenoids by synthetic strategies based on radical reactions
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
    01 Apr. 2018 - 31 Mar. 2020
    長友 優典
    【背景】分子量400-4000の中分子天然物が低分子・バイオ医薬の優位点を併せ持つポストバイオ医薬として注目を集めているが、それらを医薬品開発のリード化合物として活用する事は、その化学構造の複雑さから極めて困難な課題である。この社会的要請の高い問題の解決に向け、本研究では、反応集積型高化学選択的ラジカル反応を鍵とした官能基密集型中分子テルペノイドの実用的全合成戦略の確立を計画した。具体的には、顕著な生物活性を有する官能基密集型中分子テルペンであるタキサン類およびクラジエリン類を、高化学選択的な分子間ラジカルフラグメントカップリングおよびラジカル環形成反応を用いて超効率的に全合成する。全合成を基盤とした本研究は、天然物化学・創薬化学・有機合成化学の複合領域において、大きな学術的波及効果を生むと共に、本新学術領域研究の特長である、高次機能中分子の創製を切り開く重要な基礎研究となる。
    【方法・結果】本年度は分子間ラジカル付加反応を鍵として、がん細胞毒性を有する1-ヒドロキシタキシニンの収束的全合成研究を遂行した。アシルテルリドおよびエノンを用いたラジカル付加反応により立体選択的にA, C環を連結した。続いて、低原子価チタン試薬を用いた分子内ピナコールカップリング反応によるB環構築を行うことで、タキサン骨格を構築した。最終的に市販化合物から26工程で効率的に1-ヒドロキシタキシニン全合成を達成した。
    本成果はドイツ化学会誌Angewandte Chemie International Editionに発表した。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), The University of Tokyo, 18H04384
  • Development of convergent synthetic strategies of nucleic acid-based natural products utilizing the key three types of radical intermolecular C-C bond formation
    Grant-in-Aid for Scientific Research (C)
    Apr. 2016 - Mar. 2019
    Nagatomo Masanori
    Polyoxins J (1a) and L (1b) are important nucleoside antibiotics. The complex and densely functionalized dipeptide structures of 1a and 1b contain thymine and uracil nucleobases, respectively. We report the unified total synthesis of 1a, 1b, and their artificial analogues 1c and 1d with trifluorothymine and fluorouracil structures. Decarbonylative radical coupling between alkoxyacyl tellurides and achiral glyoxylic oxime ether led to chemo- and stereoselective construction of the ribonucleoside amino acid structures of 1a-d without damaging the preinstalled nucleobases. The high applicability of the radical-based methodology was further demonstrated by preparation of the trihydroxynorvaline moiety of 1a-d. The two amino acid fragments were connected and elaborated into 1a-d (longest linear sequence:11 steps).
    Compounds 1a and 1b assembled in this way exhibited potent activity against true fungi, while only 1d was active against Gram-positive bacteria.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), The University of Tokyo, Principal investigator, Competitive research funding, 16K08156
  • イオンチャネルを制御する巨大複雑天然物の網羅的全合成および新機能分子の創出
    科学研究費助成事業 基盤研究(A)
    Apr. 2017 - Mar. 2018
    井上 将行; 長友 優典; 伊藤 寛晃; 萩原 浩一
    生命現象の根幹をなすイオンチャネルは、感覚・感情・思考などに深くかかわり、その機能不全は多くの疾患を引き起こす。そのため、チャネルに作用する医薬品の合理的な開発は、現代科学における緊急課題である。分子量が500を超え酸素官能基が密集した巨大複雑天然物は、一般的な医薬品や天然物では実現不可能な、チャネルの高選択的阻害・活性化を可能にする。そこで、申請者は複雑天然物の全合成およびチャネルの機能解析・制御法開発のための新機能分子創出を目的とした。
    すでに申請者は、モデル基質において三成分連結反応(method A, method B)およびラジカル二量化反応(method C)の開発に成功しており、これらが分子の複雑性を一挙に増すことが出来ることを報告した。本研究提案では、method A-Cを創造的に組み合わせることによって、全合成が極めて困難なイオンチャネルに作用する巨大複雑天然物群の超効率的構築を実現する。本年度は、特にレジニフェラトキシン、スクアモシンAおよびバトラコトキシンの全合成ルートの確立を目標とした。以下に成果を報告する。
    レジニフェラトキシンは、TRPV1チャネルを介した強力な鎮痛作用を有する。5/7/6員環上に酸素官能基が密集していることが構造的特徴であり、全合成が極めて困難な巨大複雑天然物の代表例といえる。method Aを利用して合成した中間体から、すでに全合成を達成した。
    スクアモシンAは、Ca2+依存性K+チャネル活性化作用と強力な細胞毒性を有し、抗がん剤として期待されている。そのビステトラヒドロフラン構造を、method Cによって一挙に構築した。
    バトラコトキシン(電位依存性Na+チャネル活性化)の全合成では、まず、ラジカル－極性交差反応(method B)によって二成分の連結し、多数の酸素官能基を有するステロイド骨格を効率的に構築した。
    日本学術振興会, 基盤研究(A), 東京大学, 17H00886
  • Unified total synthesis and biological evaluation of natural and artificial ryanoids
    Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
    01 Apr. 2015 - 31 Mar. 2017
    Inoue Masayuki; NAGATOMO Masanori
    Dysfunction of ion channels leads to various diseases. Rational development of pharmaceuticals that modulate functions of ion channels is an urgent task in modern science. Ryanodine receptors are calcium ion release channels, and are selectively activated by ryanodine. Our study aimed at unified total synthesis and biological evaluation of ryanodine, natural and artificial ryanoids.
    In this study, we developed a new strategy for assembly of the architecturally complex structure of ryanodine, and achieved unified total synthesis of ryanodine and five other natural ryanoids. Our practical syntheses enabled us to prepare the ryanoids for detailed investigation of their various biological functions. Moreover, the fluorescent labeled ryanodine was prepared for investigation of the molecular interaction between the synthetic molecules and ryanodine receptors.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, The University of Tokyo, 15K14928
  • Development and Application of Convergent Strategies for Unified Total Syntheses of Architecturally Complex Natural Products
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    01 Apr. 2014 - 31 Mar. 2017
    Inoue Masayuki; URABE Daisuke; NAGATOMO Masanori; TAKEFUMI Kuranaga
    Architecturally complex and densely oxygenated natural products often have potent and selective biological activities. In this study, we focused on efficient, practical and flexible syntheses of these natural products based on radical chemistry. We developed an a-alkoxy radical methodology for assembly of two- and three components, and efficient radical-radical homo- and heterocoupling reactions of a-alkoxy radicals. By taking advantage of these strategies, we realized the total syntheses of various complex natural products, including ryanodine, crotophorbolone, 4-hydroxyzinowol, oubagenin, and zaragozic acid C. Moreover, these synthetic routes were applied to unified preparation of the structurally related compounds for the future structure-activity relationship studies. Because of the broadness of the reaction scope and the mildness of the conditions, these powerful strategies introduce novel technologies for expedited total synthesis of densely oxygenated natural products.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), The University of Tokyo, 26253003
  • Establishment of novel synthetic strategy utilizing two types of photo-induced direct C(sp3)-H functionalization
    Grant-in-Aid for Young Scientists (B)
    Apr. 2014 - Mar. 2016
    Nagatomo Masanori
    Development of direct transformations of C-H bonds has attracted intense attention from chemical community. We particularly focus on C(sp3)-H bond oxidations and functionalizations of multiply substituted carboskeletons.
    This time we have achieved the following three research results. 1) Enantioselective alkynylation of C(sp3)-H bonds adjacent to a nitrogen atom has been achieved using only chiral p-tolyl tert-butyldimethylsilylethynyl sulfoximine and benzophenone under photo-irradiation conditions. 2) Total synthesis of (+)-lactacystin, a potent inhibitor of the 20S proteasome has been achieved using the chemo- and stereoselective photoinduced intermolecular C(sp3)-H alkynylation and intramolecular C(sp3)-H acylation. 3) Total synthesis of (+)-zaragozic acid C, having inhibitory activity of mammalian squalene synthase, has been achieved using the chemo- and stereoselective photoinduced intramolecular C(sp3)-H acylation.
    Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), The University of Tokyo, Principal investigator, Competitive research funding, 26860009
  • a study towards total synthesis of ryanodine
    Grant-in-Aid for JSPS Fellows
    Apr. 2010 - Mar. 2012
    Nagatomo Masanori
    Ca^<2+>イオンは、様々な生物応答を司る最も重要なセカンドメッセンジャーである。その濃度を制御する細胞内蛋白質(リアノジンレセプター,RyR)には3つのサブタイプが存在し、これらが骨格筋・心筋・平滑筋・脳小胞体に異なる割合で散在し、機能することで中枢神経系が統御されている。しかし、未だ個々の機能及び作用機序の詳細については明確になっていない。そこで、RyRのサブタイプ別の機能を生物有機化学的に解明するためには、RyRと選択的に結合するリアノジンが分子プローブとして有効であると考えた。しかし、リアノジンの天然物そのものは、極めて複雑な分子骨格であるため、直戴的化学修飾による分子プローブへの誘導が困難である。申請者は、C_2対称合成中間体への二官能基同時変換と非対称化反応を鍵反応とするリアノジンの全合成及び、分子プローブの短段階合成法の確立並びに、誘導体分子プローブの創製・活性評価を立案した。
    申請者は初年度において2,5-ジメチルヒドロキノンから14工程(9度のこ官能基同時変換反応を含む)で合成したC_2対称合成中間体を四酸化オスミウム酸化によって非対称化し、反応性の高いα-オキソ-橋頭位ラジカル用いた炭素-炭素結合形成を鍵反応として、リアノジンの15位のヒドロキシ基及び3位ピロールエステルを除く全ての10連続不斉中心を有する15-デオキシ-リアノドールの合成を達成した。今年度は昨年度と同一のC_2対称合成中間体から15位に酸素官能基を有する化合物を合成し、昨年度確立したリアノジン骨格構築法を基盤としてリアノジンの3位ピロールエステルを除く全ての炭素骨格及び酸素官能基を有する重要合成中間体を合成した。本合成中間体は、4工程でのリアノドールへの変換および6工程でのリアノドールへの変換が期待できる。また本合成中間体は類縁天然物並びに、直戴的化学修飾による分子プローブへの誘導が可能な構造である。
    Japan Society for the Promotion of Science, 特別研究員奨励費, 東京大学, Principal investigator, Competitive research funding, 10J00873