Development and Application of Convergent Strategies for Unified Total Syntheses of Architecturally Complex Natural Products
Project/Area Number |
26253003
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Chemical pharmacy
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Research Institution | The University of Tokyo |
Principal Investigator |
Inoue Masayuki 東京大学, 大学院薬学系研究科(薬学部), 教授 (70322998)
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Co-Investigator(Renkei-kenkyūsha) |
URABE Daisuke 東京大学, 大学院薬学系研究科, 講師 (80503515)
NAGATOMO Masanori 東京大学, 大学院薬学系研究科, 助教 (70634161)
TAKEFUMI Kuranaga 東京大学, 大学院薬学系研究科, 助教 (70625201)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥40,560,000 (Direct Cost: ¥31,200,000、Indirect Cost: ¥9,360,000)
Fiscal Year 2016: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2015: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2014: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
|
Keywords | 合成化学 / 全合成 / 生物活性分子の設計 / 生理活性 / 収束的合成 / ラジカル反応 |
Outline of Final Research Achievements |
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.
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Report
(4 results)
Research Products
(96 results)
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[Journal Article] Design and Synthesis of Potent Substrate-based Inhibitors of the Trypanosoma cruzi Dihydroorotate Dehydrogenase2017
Author(s)
D. K. Inaoka, M. Iida, S. Hashimoto, T. Tabuchi,T. Kuranaga, E. O. Balogun, T. Honma, A. Tanaka, S. Harada, T. Nara, K. Kita, M. Inoue
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Journal Title
Bioorg. Med. Chem.
Volume: 25
Issue: 4
Pages: 1465-1470
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The Open Form Inducer Approach for Structure-Based Drug Design2016
Author(s)
D. K. Inaoka, M. Iida, T. Tabuchi, T. Honma, N. Lee, S. Hashimoto, S. Matsuoka, T. Kuranaga, K. Sato, T. Shiba, K. Sakamoto, E. O. Balogun, S. Suzuki, T. Nara, J. R. Rocha, C. A. Montanari, A. Tanaka, M. Inoue, K. Kita, S. Harada
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Journal Title
PLoS ONE
Volume: 11
Issue: 11
Pages: e0167078-e0167078
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] 2.Pharmacophore Modeling for Anti-Chagas Drug Design Using the Fragment Molecular Orbital Method2015
Author(s)
Yoshino R, Yasuo N, Inaoka DK, Hagiwara Y, Ohno K, Orita M, Inoue M, Shiba T, Harada S, Honma T, Balogun EO, da Rocha JR, Montanari CA, Kita K, Sekijima M
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Journal Title
PLoS One
Volume: 10
Issue: 5
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] 1.Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria2015
Author(s)
Inaoka DK, Shiba T, Sato D, Balogun EO, Sasaki T, Nagahama M, Oda M, Matsuoka S, Ohmori J, Honma T, Inoue M, Kita K, Harada S
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Journal Title
Int. J. Mol. Sci.
Volume: 16
Issue: 12
Pages: 15287-15308
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Total synthesis of four stereoisomers of (4Z,7Z,10Z,12E,16Z,18E)-14,20-dihydroxy-4,7,10,12,16,18-docosahexaenoic acid and their anti-inflammatory activities.2015
Author(s)
Goto T, Urabe D, Masuda K, Isobe Y, Arita M, Inoue M.
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Journal Title
J Org Chem
Volume: 80
Issue: 15
Pages: 7713-7726
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Total synthesis of four stereoisomers of (5Z,8Z,10E,14Z)-12-hydroxy-17,18-epoxy-5,8,10,14-eicosatetraenoic acid and their anti-Inflammatory activities2015
Author(s)
Goto, T.; Urabe, D.; Isobe, Y.; Arita, M.; Inoue, M.
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Journal Title
Tetrahedron
Volume: 71
Issue: 43
Pages: 8320-8332
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Identification of a Conformational Equilibrium That Determines the Efficacy and Functional Selectivity of the μ-Opioid Receptor.2015
Author(s)
Junya Okude, Takumi Ueda, Yutaka Kofuku, Motohiko Sato, Naoyuki Nobuyama, Keita Kondo, Yutaro Shiraishi, Takuya Mizumura, Kento Onishi, Mei Natsume, Masahiro Maeda, Hideki Tsujishita, Takefumi Kuranaga, Masayuki Inoue, Ichio Shimada
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Journal Title
Angewandte Chemie International Edition
Volume: 21
Issue: 52
Pages: 15771-15776
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Lysocin E is a new antibiotic that targets menaquinone in the bacterial membrane.2015
Author(s)
Hamamoto H, Urai M, Ishii K, Yasukawa J, Paudel A, Murai M, Kaji T, Kuranaga T, Hamase K, Katsu T, Su J, Adachi T, Uchida R, Tomoda H, Yamada M, Souma M, Kurihara H, Inoue M, Sekimizu K.
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Journal Title
Nature Chemical Biology
Volume: 11(2)
Issue: 2
Pages: 127-133
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Total Synthesis of Ryanodol2014
Author(s)
Masanori Nagatomo, Masaki Koshimizu, Kengo Masuda, Toshiki Tabuchi, Daisuke Urabe, Masayuki Inoue
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Journal Title
Journal of the American Chemical Society
Volume: 136
Issue: 16
Pages: 5916-5919
DOI
Related Report
Peer Reviewed
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[Journal Article] Molecular basis for the reverse reaction of African human trypanosomes glycerol kinase2014
Author(s)
Emmanuel Oluwadare Balogun, Daniel Ken Inaoka, Tomoo Shiba, Yasutoshi Kido, Chiaki Tsuge, Takeshi Nara, Takashi Aoki, Teruki Honma, Akiko Tanaka, Masayuki Inoue, Shigeru Matsuoka, Paul A.M. Michels, Kiyoshi Kita, Shigeharu Harada
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Journal Title
Molecular Microbiology
Volume: 94
Issue: 6
Pages: 1315-1329
DOI
Related Report
Peer Reviewed
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[Presentation] 薬を創る化学2017
Author(s)
井上将行
Organizer
EMPプログラム, 東京大学
Place of Presentation
東京大学(東京都, 文京区)
Year and Date
2017-01-20
Related Report
Invited
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[Presentation] 薬を創る化学2014
Author(s)
井上将行
Organizer
EMPプログラム, 東京大学
Place of Presentation
東京
Year and Date
2014-05-30
Related Report
Invited
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