1989 Fiscal Year Annual Research Report

海洋生物由来の新しい医薬素材の開発

Research Project

Project/Area Number	01307013
Research Institution	Osaka University
Principal Investigator	北川勲大阪大学, 薬学部, 教授 (20028830)
Co-Investigator(Kenkyū-buntansha)	伏谷伸宏東京大学, 農学部, 助教授 (70012010) 高野誠一東北大学, 薬学部, 教授 (20004559) 山崎幹夫千葉大学, 薬学部, 教授 (70089598) 安元健東北大学, 農学部, 教授 (20011885) 柿澤寛筑波大学, 化学系, 教授 (50015492)
Keywords	海洋生物 / 海洋天然物質 / 生物活性物質 / 海洋医薬素材 / 海洋リ-ド化合物 / 化学合成 / トキシコロジ- / ファ-マコロジ-
Research Abstract	海洋という特異な環境に生息し、適応するため、海洋生物はその進化の過程において、陸上生物とは異なる代謝系あるいは生態防御系を発展させてきたと考えられ、海洋生物が産生する二次代謝産物から、陸上生物由来の天然物質には見られない様な新しい骨格を有し、特異でかつ強力な生物活性を示すこれまでにない画期的な医薬あるいはそのリ-ド化合物が開発される可能性がきわめて大きい。豊富な未利用資源である海洋生物から、先導的医薬素材を探索し、新しい医薬開発への方途を探って、人類の健康と福祉に貢献するのが本研究の目的である。このような目的を遂行するため、現在、薬学、医学、理学、農学水産の各分野において独自に第一線で活躍している研究者20名を集約し、総合研究B「海洋生物由来の新しい医薬素材の開発」研究班を組織した。本研究班は、1)生物活性海洋天然物質の探索、2)海洋トキシコロジ-とファ-マコロジ-、3)海洋リ-ド化合物の化学合成、4)有用海洋細菌、微細藻類のバイオテクノロジ-、の4つの小グル-プに分類されている。そして、小グル-ブ内での会合、文書連絡および1989年9月と1990年1月に開催した全体会議において、活発な討論が行われ、班員間の有機的連携を深めた。その過程で、海洋医薬素材の化学的研究の発展を計ることの重要性がさらに強調された。また、1990年1月には公開シンポジウムを開催シ、班員による研究成果の公表と幅広い意見交換が行なわれた。その結果、先導的医薬素材の探索と開発を基盤とした海洋医薬素材の化学的研究を強く推進せねばならないとの結論に達し、本研究領域をさらに発展させて重点領域研究として申請するに至った。

Research Products

(49 results)

All Other

All Publications (49 results)

[Publications] I.Kitagawa: "Heterosigma-glycolipids I and II,two new galactolipids containing octadecatetraenoyl and eicosapentaenoyl residues,from a raphidophyte dinoflagellate Heterosigma sp." Chem.Pharm.Bull.,. 37. 849-851 (1989)
[Publications] M.Kobayashi: "Aragupetrosine A,a new vasodilative macrocyclic quinolizidine alkaloid from an Okinawan marine sponge Xestospongia sp." Tetrahedron Lett.,. 30. 4149-4152 (1989)
[Publications] I.Kitagawa: "The absolute stereostructure of swinholide A,a potent cytotoxic macrolide from the Okinawan marine sponge Theonella swinhoei." J.Am.Chem.Soc.,. 112. (1990)
[Publications] E.V.Wattenberg: "Structure-activity studies of the nonphorbol tumor promoter palytoxin in Swiss 3T3 cells." Cancer Res.,. 49. 5837-5842 (1989)
[Publications] T.Ooi: "Structure of cyanoviridin RR,a toxin from the bluegreen alga, Microcystis viridis." J.Appld.Phycol.,. 1. 31-38 (1989)
[Publications] I.Ohtani: "Absolute configuration of marine diterpenes possessing a xenicane skeleton." Tetrahedron Lett.,. 30. 3147-3150 (1989)
[Publications] Y.Kashman: "Ptilomycalin A:a novel polycyclic guanidine alkaloid of marine origin." J.Am.Chem.Soc.,. 111. 8925-8926 (1989)
[Publications] Y.Kawano: "Biologically active glycosides from asteroidea,XIX.Glycosphingolipids from the starfish Acanthaster planci,4.Isolation and structure of five new gangliosides." Liebigs Ann.Chem.,. 1990. 43-50 (1990)
[Publications] R.Higuchi: "Biologically active glycosides from asteroidea,XX.Glycosphingolipids from the starfish Asterina pectiniferal.Isolation and characterization of acanthacerebroside B and structure elucidation related cerebrosides." Liebigs Ann.Chem.,. 1990. 51-55 (1990)
[Publications] T.Miyamoto: "Constituents of holothuroidea,I.Isolation and structures of three triterpenoid aglycones,cucumechinol A,B,and C,from the seacucumber Cucumaria echinata." Liebigs Ann.Chem.,. 1990. 39-42 (1990)
[Publications] N.Fusetani: "Acalycixeniolides,novel norditerpenes with allene functionality from twogorgonian of the genus Acalycigorgia" Tetrahedron. 45. 1647-1652 (1989)
[Publications] S.Matsunaga: "Further kabiramides and halichondramides,cytotoxic macrolides embracing trioxazole,from the Hexabranchus egg masses." J.Org.Chem.,. 54. 1360-1363 (1989)
[Publications] N.Fusetani: "Haliclamines A and B,cytotoxic macrocyclic alkaloids from a sponge of the genus Haliclona." Tetrahedron Lett.,. 30. 6891-6894 (1989)
[Publications] J.Tanaka: "Sulfur-containing polybromoindoles from the red alga Laurencia brongniartii." Tetrahedron. 45. 7301-7310 (1989)
[Publications] T.Higa: "Bioactive polyacetylenes from stony corals" Chemistry Lett.,. 1990. 145-148 (1990)
[Publications] A.Umeyama: "Untenospongins A and B,novel furanoterpenes with coronary vasodilating activity from the Okinawan marine sponge Hippospongia sp." Aust.J.Chem.,. 42. 459-462 (1989)
[Publications] J.Kobayashi: "Theonelladins A-D,novel antineoplastic pyridine alakloids from the Okinawan marine sponge Theonella swinhoei." Tetrahedron Lett.,. 30. 4833-4836 (1989)
[Publications] T.Gonoi: "Geographutoxin-sensitive and insensitive sodium currents in mouse skeletal muscle developing in situ." J.Physiol.,. 414. 159-177 (1989)
[Publications] K.Ohuchi: "Okadaic acid and dinophysistoxin-1,non-TPA-type tumor promoters, stimulate prostaglandin E_2 production in rat peritoneal macrophages." Biochem.Biophys.Acta.,. 1013. 86-91 (1989)
[Publications] K.Ohuchi: "Stimulation of histamine release and arachidonic acid metabolism in rat peritoneal mast cells by thapsigargin,a non-TPA-type tumor promoter." Biochem.Biophys.Acta. 1003. 9-14 (1989)
[Publications] N.Hirasawa: "Occurence of histamine-production-increasing factor in the post-anaphylactic phase of allergic inflammation." Int.Arch.Allergy Appl.Immunol.,. 88. 386-393 (1989)
[Publications] E.V.Wattenberg: "Palytoxin down-modulates the epidermal growth factor receptor through a sodium-dependent pathway." J.Biol.Chem.,. 264. 213-219 (1989)
[Publications] H.Fujiki: "Sarcophytols A and B inhibit tumor promotion by teleocidin in two-stage carcinogenesis in mouse skin." J.Cancer Res.Clin.Oncol.,. 115. 25-28 (1989)
[Publications] H.Fujiki: "Codon 61 mutations in the c-Harvey-ras gene in mouse skin tumors induced by 7,12-dimethylbenz(a)anthracene plus okadaic acid class tumor promoters." Molecular Carcinogenesis. 2. 184-187 (1989)
[Publications] I.Muramatsu: "Supersensitivity to tetrodotoxin and lidocaine of anthopleurin-A treated Na channel in crayfish giant axon" European J.Pharmacol.,. (1990)
[Publications] H.Fujimoto: "Two new fungal azaphilones from Talaromyces luteus with monoamine oxidase inhibitory effect." Heterocycles. 30. 606-616 (1989)
[Publications] N.Kawahara: "Novel epitetrathiodioxopiperazines,emethallicins B and C,as potent inhibitors of compound 48/80-induced histamine release,from Emericella heterothallica." J.Chem.Soc.Chem.Commun.,. 1989. 951-952 (1989)
[Publications] Y.Satoh: "Studies on the monoamine oxidase(MAD)inhibitory potency of TL-1,isolated from a fungas Talaromyces luteus." Chem.Pharm.Bull.,. 37. 206-207 (1989)
[Publications] D.Uyakul: "Mycotoxin analysis by.means of tandem mass spectrometry" J.Assoc.Off.Anal.Chem.,. 72. 491-497 (1989)
[Publications] T.Ueda: "Synthesis and biological activity of branched chainsugar nucleosides" Nucleosides & Nucleotides. 8. 743-752 (1989)
[Publications] A.Matsuda: "Synthesis of 2′,3′ーdideoxy-3′-methylidenethymidine and 2′,3′-di-deoxy-2′,3′-didehydro-3′-methylthymidine:Deoxy-genation of the allyl alcohol system in 3′-deoxy-3′-methylidene-5-methyluridine." Heterocycles. 29. 25-28 (1989)
[Publications] Y.Yoshimura: "Synthesis of 6,6′-cyclo-5′,6′-dideoxy-1-(-D-allofuranosyl)cytosine and related nucleosides." Chem.Pharm.Bull.,. 37. 660-664 (1989)
[Publications] K.Kohda: "Mechanistic aspects of the cytocidal action of ulithiacyclamide on mouse leukemia L1210 cells in vitro." Biochem.Pharmacol.,. 38. 4497-4500 (1989)
[Publications] K.Kohda: "Ulithiamide is cytotoxic against L1210 in vitro and inhibits both DNA and RNA syntheses." Biochem.Pharmacol.,. 38. 4500-4502 (1989)
[Publications] S.Takano: "Concise synthesis of C_2-symmetric trans-2,5-dioxymethylpyrrolidine derivatives by novel cyclization." Tetrahedron Lett.,. 30. 3805-3806 (1989)
[Publications] S.Takano: "Enantiocontrolled synthesis of(+)-aphanorphine from(R)-O-benzylglycidol:assignment of absolute configuration." J.Chem.Soc.Chem.Commun.,. 1989. 1591-1592 (1989)
[Publications] S.Takano: "The enantioselective total synthesis of natural(-)-aphanorphine" J.chem.Soc.Chem.Commun.,. 1990. (1990)
[Publications] T.Lirdwitayaprasit: "Biochemical processes during the cyst formation of marine formation of marine phytoflagellates" The proceeding of 4th International Conference on Toxic Marine phytoplankton. 294-299 (1990)
[Publications] T.Okaichi: "Countermeasures aimed at the Chattonella red tide in Shido Bay,the Seto Inland Sea in 1987." The Proceeding of the Second Asian Fisheries Forum. inpress. (1990)
[Publications] D.F.Hwang: "Tetrodotoxin-producing bacteria from the blue-ringed octopus Octopus maculosus." Marine Biology. 100. 327-332 (1989)
[Publications] H.K.Do: "Identification of deep-sea-sediment bacteria which produce tetrodotoxin." Applied and Environmental Microbiology. (1990)
[Publications] M.Murakami: "Cytotoxic polyunsaturated fatty acid from Pediastrum." phytochemistry. 28. 625-626 (1989)
[Publications] K.Yamaguchi: "Screening of angiotensin converting enzyme inhibitory activities in microalgae" J.Appl.Phycol.,. 1. (1989)
[Publications] T.Yasumoto: "Interspecies distribution and biogenetic origin of tetrodotoxin and its deribatives." Pure&Appl.Chem.,. 61. 505-508 (1989)
[Publications] M.Murata: "Structures of ciguatoxin and its congener" J.Am.Chem.Soc.,. 111. 8929-8931 (1989)
[Publications] M.Murata: "A probable partial structure of ciguatoxin isolated from the Moray eel Bymnothorax javanicus." Tetrahedron Lett.,. 30. 3793-3796 (1989)
[Publications] D.Uemura: "Studies in natural products chemistry,Vol.5(B)“Antitumor polyethers from marine animals"" Elsvier(Atta-ur-Rahman ed.), 377-401 (1989)
[Publications] M.Kobayashi: "Bioorganic Marine Chemistry,Vol.3.pp 71ー84.“Con shell toxins and the mechanisms of their pharmacological action." SpringerーVerlag,Berlin(P.J.Scheuer ed.), 175 (1989)
[Publications] T.Shioiri: "Studies in Natural Products Chemistry,Vol.4C“Total synthesis of cytotoxic cyclic peptides of marine origin"" Elsevier(AttaーurーRahman ed.), 83-110 (1989)

1989 Fiscal Year Annual Research Report

海洋生物由来の新しい医薬素材の開発

Principal Investigator

北川 勲 大阪大学, 薬学部, 教授 (20028830)

Research Products

[Publications] I.Kitagawa: "Heterosigma-glycolipids I and II,two new galactolipids containing octadecatetraenoyl and eicosapentaenoyl residues,from a raphidophyte dinoflagellate Heterosigma sp." Chem.Pharm.Bull.,. 37. 849-851 (1989)

[Publications] M.Kobayashi: "Aragupetrosine A,a new vasodilative macrocyclic quinolizidine alkaloid from an Okinawan marine sponge Xestospongia sp." Tetrahedron Lett.,. 30. 4149-4152 (1989)

[Publications] I.Kitagawa: "The absolute stereostructure of swinholide A,a potent cytotoxic macrolide from the Okinawan marine sponge Theonella swinhoei." J.Am.Chem.Soc.,. 112. (1990)

[Publications] E.V.Wattenberg: "Structure-activity studies of the nonphorbol tumor promoter palytoxin in Swiss 3T3 cells." Cancer Res.,. 49. 5837-5842 (1989)

[Publications] T.Ooi: "Structure of cyanoviridin RR,a toxin from the bluegreen alga, Microcystis viridis." J.Appld.Phycol.,. 1. 31-38 (1989)

[Publications] I.Ohtani: "Absolute configuration of marine diterpenes possessing a xenicane skeleton." Tetrahedron Lett.,. 30. 3147-3150 (1989)

[Publications] Y.Kashman: "Ptilomycalin A:a novel polycyclic guanidine alkaloid of marine origin." J.Am.Chem.Soc.,. 111. 8925-8926 (1989)

[Publications] Y.Kawano: "Biologically active glycosides from asteroidea,XIX.Glycosphingolipids from the starfish Acanthaster planci,4.Isolation and structure of five new gangliosides." Liebigs Ann.Chem.,. 1990. 43-50 (1990)

[Publications] R.Higuchi: "Biologically active glycosides from asteroidea,XX.Glycosphingolipids from the starfish Asterina pectiniferal.Isolation and characterization of acanthacerebroside B and structure elucidation related cerebrosides." Liebigs Ann.Chem.,. 1990. 51-55 (1990)

[Publications] T.Miyamoto: "Constituents of holothuroidea,I.Isolation and structures of three triterpenoid aglycones,cucumechinol A,B,and C,from the seacucumber Cucumaria echinata." Liebigs Ann.Chem.,. 1990. 39-42 (1990)

[Publications] N.Fusetani: "Acalycixeniolides,novel norditerpenes with allene functionality from twogorgonian of the genus Acalycigorgia" Tetrahedron. 45. 1647-1652 (1989)

[Publications] S.Matsunaga: "Further kabiramides and halichondramides,cytotoxic macrolides embracing trioxazole,from the Hexabranchus egg masses." J.Org.Chem.,. 54. 1360-1363 (1989)

[Publications] N.Fusetani: "Haliclamines A and B,cytotoxic macrocyclic alkaloids from a sponge of the genus Haliclona." Tetrahedron Lett.,. 30. 6891-6894 (1989)

[Publications] J.Tanaka: "Sulfur-containing polybromoindoles from the red alga Laurencia brongniartii." Tetrahedron. 45. 7301-7310 (1989)

[Publications] T.Higa: "Bioactive polyacetylenes from stony corals" Chemistry Lett.,. 1990. 145-148 (1990)

[Publications] A.Umeyama: "Untenospongins A and B,novel furanoterpenes with coronary vasodilating activity from the Okinawan marine sponge Hippospongia sp." Aust.J.Chem.,. 42. 459-462 (1989)

[Publications] J.Kobayashi: "Theonelladins A-D,novel antineoplastic pyridine alakloids from the Okinawan marine sponge Theonella swinhoei." Tetrahedron Lett.,. 30. 4833-4836 (1989)

[Publications] T.Gonoi: "Geographutoxin-sensitive and insensitive sodium currents in mouse skeletal muscle developing in situ." J.Physiol.,. 414. 159-177 (1989)

[Publications] K.Ohuchi: "Okadaic acid and dinophysistoxin-1,non-TPA-type tumor promoters, stimulate prostaglandin E_2 production in rat peritoneal macrophages." Biochem.Biophys.Acta.,. 1013. 86-91 (1989)

[Publications] K.Ohuchi: "Stimulation of histamine release and arachidonic acid metabolism in rat peritoneal mast cells by thapsigargin,a non-TPA-type tumor promoter." Biochem.Biophys.Acta. 1003. 9-14 (1989)

[Publications] N.Hirasawa: "Occurence of histamine-production-increasing factor in the post-anaphylactic phase of allergic inflammation." Int.Arch.Allergy Appl.Immunol.,. 88. 386-393 (1989)

[Publications] E.V.Wattenberg: "Palytoxin down-modulates the epidermal growth factor receptor through a sodium-dependent pathway." J.Biol.Chem.,. 264. 213-219 (1989)

[Publications] H.Fujiki: "Sarcophytols A and B inhibit tumor promotion by teleocidin in two-stage carcinogenesis in mouse skin." J.Cancer Res.Clin.Oncol.,. 115. 25-28 (1989)

[Publications] H.Fujiki: "Codon 61 mutations in the c-Harvey-ras gene in mouse skin tumors induced by 7,12-dimethylbenz(a)anthracene plus okadaic acid class tumor promoters." Molecular Carcinogenesis. 2. 184-187 (1989)

[Publications] I.Muramatsu: "Supersensitivity to tetrodotoxin and lidocaine of anthopleurin-A treated Na channel in crayfish giant axon" European J.Pharmacol.,. (1990)

[Publications] H.Fujimoto: "Two new fungal azaphilones from Talaromyces luteus with monoamine oxidase inhibitory effect." Heterocycles. 30. 606-616 (1989)

[Publications] N.Kawahara: "Novel epitetrathiodioxopiperazines,emethallicins B and C,as potent inhibitors of compound 48/80-induced histamine release,from Emericella heterothallica." J.Chem.Soc.Chem.Commun.,. 1989. 951-952 (1989)

[Publications] Y.Satoh: "Studies on the monoamine oxidase(MAD)inhibitory potency of TL-1,isolated from a fungas Talaromyces luteus." Chem.Pharm.Bull.,. 37. 206-207 (1989)

[Publications] D.Uyakul: "Mycotoxin analysis by.means of tandem mass spectrometry" J.Assoc.Off.Anal.Chem.,. 72. 491-497 (1989)

[Publications] T.Ueda: "Synthesis and biological activity of branched chainsugar nucleosides" Nucleosides & Nucleotides. 8. 743-752 (1989)

[Publications] A.Matsuda: "Synthesis of 2′,3′ーdideoxy-3′-methylidenethymidine and 2′,3′-di-deoxy-2′,3′-didehydro-3′-methylthymidine:Deoxy-genation of the allyl alcohol system in 3′-deoxy-3′-methylidene-5-methyluridine." Heterocycles. 29. 25-28 (1989)

[Publications] Y.Yoshimura: "Synthesis of 6,6′-cyclo-5′,6′-dideoxy-1-(-D-allofuranosyl)cytosine and related nucleosides." Chem.Pharm.Bull.,. 37. 660-664 (1989)

[Publications] K.Kohda: "Mechanistic aspects of the cytocidal action of ulithiacyclamide on mouse leukemia L1210 cells in vitro." Biochem.Pharmacol.,. 38. 4497-4500 (1989)

[Publications] K.Kohda: "Ulithiamide is cytotoxic against L1210 in vitro and inhibits both DNA and RNA syntheses." Biochem.Pharmacol.,. 38. 4500-4502 (1989)

[Publications] S.Takano: "Concise synthesis of C_2-symmetric trans-2,5-dioxymethylpyrrolidine derivatives by novel cyclization." Tetrahedron Lett.,. 30. 3805-3806 (1989)

[Publications] S.Takano: "Enantiocontrolled synthesis of(+)-aphanorphine from(R)-O-benzylglycidol:assignment of absolute configuration." J.Chem.Soc.Chem.Commun.,. 1989. 1591-1592 (1989)

[Publications] S.Takano: "The enantioselective total synthesis of natural(-)-aphanorphine" J.chem.Soc.Chem.Commun.,. 1990. (1990)

[Publications] T.Lirdwitayaprasit: "Biochemical processes during the cyst formation of marine formation of marine phytoflagellates" The proceeding of 4th International Conference on Toxic Marine phytoplankton. 294-299 (1990)

[Publications] T.Okaichi: "Countermeasures aimed at the Chattonella red tide in Shido Bay,the Seto Inland Sea in 1987." The Proceeding of the Second Asian Fisheries Forum. inpress. (1990)

[Publications] D.F.Hwang: "Tetrodotoxin-producing bacteria from the blue-ringed octopus Octopus maculosus." Marine Biology. 100. 327-332 (1989)

[Publications] H.K.Do: "Identification of deep-sea-sediment bacteria which produce tetrodotoxin." Applied and Environmental Microbiology. (1990)

[Publications] M.Murakami: "Cytotoxic polyunsaturated fatty acid from Pediastrum." phytochemistry. 28. 625-626 (1989)

[Publications] K.Yamaguchi: "Screening of angiotensin converting enzyme inhibitory activities in microalgae" J.Appl.Phycol.,. 1. (1989)

[Publications] T.Yasumoto: "Interspecies distribution and biogenetic origin of tetrodotoxin and its deribatives." Pure&Appl.Chem.,. 61. 505-508 (1989)

[Publications] M.Murata: "Structures of ciguatoxin and its congener" J.Am.Chem.Soc.,. 111. 8929-8931 (1989)

[Publications] M.Murata: "A probable partial structure of ciguatoxin isolated from the Moray eel Bymnothorax javanicus." Tetrahedron Lett.,. 30. 3793-3796 (1989)

[Publications] D.Uemura: "Studies in natural products chemistry,Vol.5(B)“Antitumor polyethers from marine animals"" Elsvier(Atta-ur-Rahman ed.), 377-401 (1989)

[Publications] M.Kobayashi: "Bioorganic Marine Chemistry,Vol.3.pp 71ー84.“Con shell toxins and the mechanisms of their pharmacological action." SpringerーVerlag,Berlin(P.J.Scheuer ed.), 175 (1989)

[Publications] T.Shioiri: "Studies in Natural Products Chemistry,Vol.4C“Total synthesis of cytotoxic cyclic peptides of marine origin"" Elsevier(AttaーurーRahman ed.), 83-110 (1989)

北川勲大阪大学, 薬学部, 教授 (20028830)