Research and development of bioactive marine natural products

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390001
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: KOBAYASHI Jun'ichi 北海道大学, 大学院・薬学研究院, 教授 (90221241)
• Co-Investigator(Kenkyū-buntansha): KUBOTA Takaaki 北海道大学, 大学院・薬学研究院, 准教授 (60399954) ; ISHIYAMA Haruaki 北海道大学, 大学院・薬学研究院, 助教 (70333622)
• Project Period (FY): 2008 – 2010
• Keywords: 機能性天然分子 / 海洋天然物 / 分子標的 / 天然物ライブラリー / 海洋生物

Research Abstract

Investigation of extracts of an Okinawan marine organisms (sponge, tunicate, and dinoflagellate etc.) resulted in the isolation of new manzamine alkaloids exhibiting antimalarial and antitrypanosomal activities, new pyridinium alkaloids exhibiting acetylcholine esterase inhibitory activity, and new terpenoid quinones exhibiting tyrosine kinase inhibitory activity. In addition, many new compounds that show cytotoxic activity (pyridine alkaloids, beta-carboline alkaloids, bromotyrosine alkaloids, a macrolide, and sesquiterpenoids) and anti-microbial activity (bromopyrrole alkaloids, bromotyrosine alkaloids, triterpenoids) were isolated from the marine organisms. The absolute stereochemistries of known cytotoxic macrolides, previously isolated from dinoflagellete by our group, were also elucidated.

Research Products

• [Journal Article] Pyrinodemins E and F, new 3-alkylpyridine alkaloids from sponge Amphimedon sp. (2011)
  • Author(s): Kura, K.; Kubota, T.; Fromont, J. Kobayashi, J.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 21 Pages: 267-270
  • DOI: DOI:10.1016/j.bmcl.2010.11.020.
  • Peer Reviewed
• [Journal Article] Hyrtioseragamines A and B, new alkaloids from the sponge Hyrtios species (2011)
  • Author(s): Takahashi, Y.; Iinuma, Y.; Kubota, T.; Tsuda, M.; ekiguchi, M.; Mikami, Y.; Fromont, J.; Kobayashi, J.
  • Journal Title: Org. Lett. Volume: 13 Pages: 628-631
  • DOI: DOI:10.1021/ol102867x.
  • Peer Reviewed
• [Journal Article] Halichonadins G-J, new sesquiterpenoids from a sponge Halichondria sp. (2011)
  • Author(s): Suto, S.; Tanaka, N.; Fromont, J.; Kobayashi, J.
  • Journal Title: Tetrahedron Lett. Volume: 52 Pages: 3470-3473
  • DOI: DOI:10.1016/j.tetlet.2011.04.105
  • Peer Reviewed
• [Journal Article] Nakijinamines C-E, new heteroaromatic alkaloids from the sponge Suberites species (2011)
  • Author(s): Takahashi, Y.; Kubota, T.; Shibazaki, A.; Gonoi, T.; Fromont, J.; Kobayashi, J.
  • Journal Title: Org. Lett. Volume: 13 Pages: 3016-3019
  • DOI: DOI:10.1021/ol2008473.
  • Peer Reviewed
• [Journal Article] Stelliferins J-N, isomalabaricane-type triterpenoids from Okinawan marine sponge Rhabdastrella cf. globostellata (2011)
  • Author(s): Tanaka, N.; Momose, R.; Shibazaki, A.; Gonoi, T.; Fromont, J.; Kobayashi, J.
  • Journal Title: Tetrahedron Volume: 67 Pages: 6689-6696
  • DOI: DOI:10.1016/j.tet.2011.04.095.
  • Peer Reviewed
• [Journal Article] Eudistomidins H-K, new b-carboline alkaloids from the Okinawan marine tunicate Eudistoma glaucus (2011)
  • Author(s): Suzuki, T.; Kubota, T.; Kobayashi, J.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 21 Pages: 4220-4223
  • DOI: DOI:10.1016/j.bmcl.2011.05.072.
  • Peer Reviewed
• [Journal Article] Platisidines A-C, N-methyl pyridinium alkaloids from an Okinawan marine sponge of Plakortis species (2010)
  • Author(s): Kubota, T.; Ishiguro, Y.; Yamamoto, S.; Fromont, J.; Kobayashi, J.
  • Journal Title: Heterocycles Volume: 80 Pages: 1407-1412
  • DOI: DOI:10.3987/COM-09-S(S)131.
  • Peer Reviewed
• [Journal Article] Nakijiquinones J-R, sesquiterpenoid quinones from Okinawan marine sponges (2010)
  • Author(s): Takahashi, Y.; Ushio, M.; Kubota, T.; Yamamoto, S.; Fromont, J.; Kobayashi, J.
  • Journal Title: J. Nat. Prod. Volume: 73 Pages: 467-471
  • DOI: DOI:10.1021/np900470e.
  • Peer Reviewed
• [Journal Article] Amphidinolide C3, a new cytotoxic 25-membered macrolide from marine dinoflagellate Amphidinium sp. (2010)
  • Author(s): Kubota, T.; Suzuki, A.; Yamada, M.; Baba, S.; Kobayashi, J.
  • Journal Title: Heterocycles Volume: 82 Pages: 333-338
  • DOI: DOI:10.3987/COM-10-S(E)3.
  • Peer Reviewed
• [Journal Article] Untenolide A, a new polyketide from an Okinawan marine sponge Plakortis sp. (2010)
  • Author(s): Ishiguro, Y.; Kubota, T.; Fromont, J.; Shiro, M.; Kobayashi, J.
  • Journal Title: Tetrahedron Lett. Volume: 51 Pages: 4023-4026
  • DOI: DOI:10.1016/j.tetlet.2010.05.085.
  • Peer Reviewed
• [Journal Article] Eudistomidin G, a new b-carboline alkaloid from the Okinawan marine tunicate Eudistoma glaucus and structure revision of eudistomidin B (2010)
  • Author(s): Takahashi, Y.; Ishiyama, H.; Kubota, T.; Kobayashi, J.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 20 Pages: 4100-4103
  • DOI: DOI:10.1016/j.bmcl.2010.05.071.
  • Peer Reviewed
• [Journal Article] Ceratinadins A-C, new bromotyrosine alkaloids from an Okinawan marine sponge Pseudoceratina sp. (2010)
  • Author(s): Kon, Y.; Kubota, T.; Shibazaki A.; Gonoi, T.; Kobayashi, J.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 20 Pages: 4569-4572
  • DOI: DOI:10.1016/j.bmcl.2010.06.015.
  • Peer Reviewed
• [Journal Article] Nakijiquinones E and F, new dimeric sesquiterpenoid quinones from marine sponge (2009)
  • Author(s): Takahashi, Y.; Kubota, T.; Kobayashi, J.
  • Journal Title: Bioorg. Med. Chem. Volume: 17 Pages: 2185-2188
  • DOI: DOI:10.1016/j.bmc.2008.10.080.
  • Peer Reviewed
• [Journal Article] Zamamidines A & B, new manzamine alkaloids from sponge Amphimedon species (2009)
  • Author(s): Takahashi, Y.; Kubota, T.; Fromont, J.; Kobayashi, J.
  • Journal Title: Org. Lett. Volume: 11 Pages: 21-24
  • DOI: DOI:10.1021/ol802251q.
  • Peer Reviewed
• [Journal Article] Total synthesis of amphidinolactone A and its absolute configuration (2009)
  • Author(s): Hangyou, M.; Ishiyama, H.; Takahashi, Y.; Kubota, T.; Kobayashi, J.
  • Journal Title: Tetrahedron Lett. Volume: 50 Pages: 1475-1477
  • DOI: DOI:10.1016/j.tetlet.2009.01.065.
  • Peer Reviewed
• [Journal Article] Zamamidine C, 3,4-dihydro-6-hydroxy-10,11-epoxymanzamine A, and 3,4-dihydromanzamine J N-oxide, new manzamine alkaloids from sponge Amphimedon sp. (2009)
  • Author(s): Yamada, M.; Takahashi, Y.; Kubota, T.; Fromont, J.; Ishiyama, A.; Otoguro, K.; Yamada, H.; Omura, S; Kobayashi, J.
  • Journal Title: Tetrahedron Volume: 65 Pages: 2313-2317
  • DOI: DOI:10.1016/j.tet.2009.01.032.
  • Peer Reviewed
• [Journal Article] Tyrokeradines A and B, new bromotyrosine alkaloids with an imidazolyl-quinolinone moiety from a Verongid sponge (2009)
  • Author(s): Mukai, H.; Kubota, T.; Aoyama, K.; Mikami, Y.; Fromont, J.; Kobayashi, J.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 19 Pages: 1337-1339
  • DOI: DOI:10.1016/j.bmcl.2009.01.056.
  • Peer Reviewed
• [Journal Article] Bromopyrrole alkaloids from marine sponges of the genus Agelas (2009)
  • Author(s): Yasuda, T.; Araki, A.; Kubota, T.; Ito, J.; Mikami, Y.; Fromont, J.; Kobayashi, J.
  • Journal Title: J. Nat. Prod. Volume: 72 Pages: 488-491
  • DOI: DOI:10.1021/np800645q.
  • Peer Reviewed
• [Journal Article] Total synthesis and biological evaluation of amphidinolide V and analogues (2009)
  • Author(s): Furstner, A.; Flugge, S.; Larionov, O.; Takahashi, Y.; Kubota, T.; Kobayashi, J.
  • Journal Title: Chem. Eur. J. Volume: 15 Pages: 4011-4029
  • DOI: DOI:10.1002/chem.200802068
  • Peer Reviewed
• [Journal Article] Nagelamides Q and R, novel dimeric bromopyrrole alkaloids from sponges Agelas sp. (2009)
  • Author(s): Araki, A.; Kubota, T.; Aoyama, K.; Mikami, Y.; Fromont, J.; Kobayashi, J.
  • Journal Title: Org. Lett. Volume: 11 Pages: 1785-1788
  • DOI: DOI:10.1021/ol900328c.
  • Peer Reviewed
• [Journal Article] Plakoridine C, a novel piperidine alkaloid from an Okinawan marine sponge Plakortis sp. (2009)
  • Author(s): Ishiguro, Y.; Kubota, T.; Ishiuchi, K.; Fromont, J.; Kobayashi, J.
  • Journal Title: Tetrahedron Lett. Volume: 50 Pages: 3202-3204
  • DOI: DOI:10.1016/j.tetlet.2009.01.135.
  • Peer Reviewed
• [Journal Article] Synthesis of hybrid analogues of caffeine and eudistomin D and its affinity for adenosine receptors (2009)
  • Author(s): Ishiyama, H.; Nakajima, H.; Nakata, H.; Kobayashi, J.
  • Journal Title: Bioorg. Med. Chem. Volume: 17 Pages: 4280-4284
  • DOI: DOI:10.1016/j.bmc.2009.05.036.
  • Peer Reviewed
• [Journal Article] Total synthesis of amphidinolide Q (2009)
  • Author(s): Hangyou, M.; Ishiyama, H.; Takahashi, Y.; Kobayashi, J.
  • Journal Title: Org. Lett. Volume: 11 Pages: 5046-5049
  • DOI: DOI:10.1021/ol902026f.
  • Peer Reviewed
• [Journal Article] Benzosceptrin C, a new dimeric bromopyrrole alkaloid from sponge Agelas sp. (2009)
  • Author(s): Kubota, T.; Araki, A.; Yasuda, T.; Tsuda, M.; Fromont, J.; Aoyama, K.; Mikami, Y.; Walchli, M. R.; Kobayashi, J.
  • Journal Title: Tetrahedron Lett. Volume: 50 Pages: 7268-7270
  • DOI: DOI:10.1016/j.tetlet.2009.10.017.
  • Peer Reviewed
• [Journal Article] Xestosaprol C, a new pentacyclic hydroquinone sulfate from a arine sponge Xestospongia sapra (2008)
  • Author(s): Kubota, T.; Kon, Y.; Kobayashi, J.
  • Journal Title: Heterocycles Volume: 76 Pages: 1571-1575
  • DOI: DOI:10.3987/COM-08-S(N)122.
  • Peer Reviewed
• [Journal Article] Absolute stereochemistry of amphidinolide Q (2008)
  • Author(s): Takahashi, Y.; Kubota, T.; Fukushi, E.; Kawabata, J.; Kobayashi, J.
  • Journal Title: Org. Lett. Volume: 10 Pages: 3709-3711
  • DOI: DOI:10.1021/ol8013123.
  • Peer Reviewed
• [Journal Article] Nakijiquinones G-I, new sesquiterpenoid quinones from marine sponge (2008)
  • Author(s): Takahashi, Y.; Kubota, T.; Ito, J.; Mikami, Y.; Kobayashi, J.
  • Journal Title: Bioorg. Med. Chem. Volume: 16 Pages: 7561-7564
  • DOI: DOI:10.1016/j.bmc.2008.07.028.
  • Peer Reviewed
• [Journal Article] Nagelamides M and N, new bromopyrrole alkaloids from sponge Agelas speices (2008)
  • Author(s): Kubota, T.; Araki, A.; Ito, J.; Mikami, Y.; Fromont, J.; Kobayashi, J.
  • Journal Title: Tetrahedron Volume: 64 Pages: 10810-10813
  • DOI: DOI:10.1016/j.tet.2008.09.039.
  • Peer Reviewed
• [Presentation] 沖縄産ホヤEudistoma glaucus由来の新規β-カルボリンアルカロイドEudistomidinH-Kの構造 (2012)
  • Author(s): 久保田高明(小林淳一)
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学(札幌市)
  • Year and Date: 2012-03-30
• [Presentation] 沖縄産Halichondria属海綿より単離した新規セスキテルペノイドの構造 (2011)
  • Author(s): 須藤翔平(小林淳一)
  • Organizer: 日本薬学会北海道支部第137回例会
  • Place of Presentation: 北海道大学学術交流会館(札幌市)
  • Year and Date: 2011-12-03
• [Presentation] 特異な構造を有する天然物の探索ならびに生合成研究 (2011)
  • Author(s): 久保田高明(小林淳一)
  • Organizer: 若手研究者のための有機化学札幌セミナー2011(招待講演)
  • Place of Presentation: 北海道大学大学院農学研究院(札幌市)
  • Year and Date: 2011-11-28
• [Presentation] 沖縄産Jaspis属海綿由来の新規トリテルペノイドstelliferinH-Lの構造 (2011)
  • Author(s): 百瀬嶺(小林淳一)
  • Organizer: 日本生薬学会北海道支部第35回例会
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2011-05-21
• [Presentation] 沖縄産Plakortis属海綿由来の新規ポリケタイドUntenolide Aの構造 (2011)
  • Author(s): 久保田高明(小林淳一)
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: ツインメッセ静岡(静岡県)
  • Year and Date: 2011-03-31
• [Presentation] 沖縄産海綿Jaspisstelliferaより単離した新規テルペノイドの構造 (2011)
  • Author(s): 田中直伸(小林淳一)
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: ツインメッセ静岡(静岡県)
  • Year and Date: 2011-03-28
• [Presentation] Total Synthesis of Amphidinolide Q (2010)
  • Author(s): 石山玄明(小林淳一)
  • Organizer: 2010 International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Hilton Hawaiian Village (USA)
  • Year and Date: 2010-12-18
• [Presentation] 渦鞭毛藻由来の12員環マクロリド・Amphidinolide Qの全合成 (2010)
  • Author(s): 石山玄明(小林淳一)
  • Organizer: 第52回天然有機化合物討論会
  • Place of Presentation: グランシップ静岡県コンベンションアーツセンター(静岡県)
  • Year and Date: 2010-09-29
• [Presentation] 沖縄産海綿由来の新規ブロモチロシンアルカロイドCeratinadin A-Cの構造 (2010)
  • Author(s): 久保田高明(小林淳一)
  • Organizer: 日本生薬学会第57回年会
  • Place of Presentation: パークウエストンホテル & ウエディング(徳島県)
  • Year and Date: 2010-09-26
• [Presentation] 渦鞭毛藻由来マクロリド・Amphidinolactone Aの全合成と立体化学の解明 (2009)
  • Author(s): 萩行正博(小林淳一)
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 20090326-28
• [Presentation] 沖縄産海綿由来の新規ブロモチロシンアルカロイドTyrokeradine AおよびBの構造 (2009)
  • Author(s): 久保田高明(小林淳一)
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 20090326-28
• [Presentation] 沖縄産Agelas属海綿より単離した新規ブロモピロールアルカロイドの構造 (2008)
  • Author(s): 荒木敦(小林淳一)
  • Organizer: 第17回天然薬物の開発と応用シンポジウ厶
  • Place of Presentation: 九州大学医学部百年講堂(福岡市)
  • Year and Date: 20081113-14
• [Presentation] Structures and activities of new terpenoid quinones from Okinawan sponges (2008)
  • Author(s): 久保田高明(小林淳一)
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場、(愛知県)
  • Year and Date: 20081028-30
• [Presentation] Chemistry and biology of bioactive natural products from marine and other sources (2008)
  • Author(s): 小林淳一
  • Organizer: 7th Joint Meeting of AFERP, ASP, GA, PSE & SIF
  • Place of Presentation: Athens convention bureau (Greece)
  • Year and Date: 20080803-08
• [Presentation] 沖縄産海綿より単離した新規テルペノイドキノン類の構造と活性 (2008)
  • Author(s): 久保田高明(小林淳一)
  • Organizer: 第12回日本がん分子標的治療研究会総会
  • Place of Presentation: 学術総合センター(東京都)
  • Year and Date: 20080626-27
• [Presentation] Bioactive metabolites from dinoflagellate Amphidinium sp., Natural Products Discovery and Production II : Celebrating the Successes of Traditional and Novel Culture Sources (2008)
  • Author(s): 小林淳一
  • Organizer: Engineering Conference International
  • Place of Presentation: Whistler (Canada)
  • Year and Date: 20080622-26
• [Presentation] Chemistry and biology of Okinawan marine natural products (2008)
  • Author(s): 小林淳一
  • Organizer: IUPAC International Conference on Biodiversity and Natural Products
  • Place of Presentation: Delta Prince Edward Hotel (Canada)
  • Year and Date: 20080613-18
• [Presentation] アデノシン受容体に特異的に作用する機能性分子の探索 (2008)
  • Author(s): 小林淳一
  • Organizer: 日本ケミカルバイオロジー研究会第3回年会
  • Place of Presentation: 学術総合センター(東京都)
  • Year and Date: 20080519-20
• [Presentation] 沖縄産海綿由来の新規ブロモピロールアルカロイドの構造 (2008)
  • Author(s): 荒木敦(小林淳一)
  • Organizer: 第50回天然有機化合物討論会
  • Place of Presentation: 福岡国際会議場(福岡県)
  • Year and Date: 2008-09-30
• [Presentation] 沖縄産海綿より単離したnakijiquinone/metachromin類の構造と生物活性 (2008)
  • Author(s): 高橋洋平(小林淳一)
  • Organizer: 第50回天然有機化合物討論会
  • Place of Presentation: 福岡国際会議場(福岡県)
  • Year and Date: 2008-09-30
• [Presentation] AmphidinolactoneAの立体化学解明を目指した合成研究 (2008)
  • Author(s): 萩行正博(小林淳一)
  • Organizer: 日本生薬学会北海道支部第32回例会
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2008-05-10
• [Presentation] 海綿Xestospongia sp.由来のXestoquinone関連化合物の構造 (2008)
  • Author(s): 今祐司(小林淳一)
  • Organizer: 日本生薬学会北海道支部第32回例会
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2008-05-10
• [Presentation] 海綿Plakortis sp.のManzamenone関連化合物の構造 (2008)
  • Author(s): 石黒悠一朗(小林淳一)
  • Organizer: 日本生薬学会北海道支部第32回例会
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2008-05-10
• [Book] Bioactive metabolites from marine dinoflagellates (2010)
  • Author(s): Kobayashi, J.; Kubota, T.
  • Total Pages: 263-325
  • Publisher: In Comprehensive Natural Products II : Chemistry and Biology; Mander, L., Lui, H.-W., Eds.; Elsevier Science : Oxford
• [Remarks]
  • URL: http://www.pharm.hokudai.ac.jp/tennen/index.html