1995 Fiscal Year Annual Research Report

特異な生理活性を示す微量天然物の量的供給を志向した合成研究

Research Project

Project/Area Number	05303011
Research Institution	Ngasaki University
Principal Investigator	入江寛長崎大学, 薬学部, 教授 (00025686)
Co-Investigator(Kenkyū-buntansha)	芳本忠長崎大学, 薬学部, 教授 (60088870) 富岡清大阪大学, 産業科学研究所, 教授 (50114575) 藤井信孝京都大学, 薬学部, 教授 (60109014) 柴崎正勝東京大学, 薬学部, 教授 (30112767) 橋本俊一北海道大学, 薬学部, 教授 (80107391)
Keywords	生理活性微量天然物合成 / 不斉合成 / 有機金属化合物の利用 / アミノ酸修飾 / 不斉合成素子の開発 / 有用酵素の量的供給
Research Abstract	本研究は天然から極微量にしか得られないが、特異な生理活性を示す化合物を、独自の方法を基盤として合成し、その生理活性発現の機構を詳細に研究しようとしている研究者にその化合物を提供することを目的として行われる研究である。よって、各研究者の研究対象は多岐に渡る。一方、天然物のほとんどが光学活性体として得られるので、合成品もまた光学活性体でなければならない。ここに不斉合成に関する基礎的研究が必要となる。本研究組織を形成する研究者の内、橋本、広井、鈴木、富岡、冨士は不斉合成のための基礎的研究を、小笠原、柴崎、津田、大船、兼松、西沢、入江、宮下、畑山は基礎的反応の開発を志向しつつ、生理活性天然物の合成を、藤井、芳本はアミノ酸関連の研究を、特に芳本はバイオテクノロジーの手法を駆使して有用酵素の量産と、酵素の活性部位の解明を志向した研究を行っている。この他、高橋はコンピュタ-を巧みに利用してより有効な物質の分子設計を行い、藤田は酵素モデルを用いて酵素の特異性に迫る研究を行っている。また、上村は海洋生物を対象にして、特異な生理活性を示す化合物の検索を鋭意行っている。以上の研究者はそれぞれ卓越した研究成果を挙げつつある。その成果は最終年度に提出する成果報告書にまとめられている。一、二の研究成果を取り上げれば、柴崎による不斉ヘック反応に関する研究は世界的にも高い評価を受けている。また、入江、宮下、畑山によって行われたクモ毒素の全合成も一つの成果として挙げられよう。本成果はクモ毒素の量的供給を可能にした点で評価され、長崎新聞にも取り上げられたことを付記しておく。

Research Products

(30 results)

All Other

All Publications (30 results)

[Publications] M.Miyashita: "Total Synthesis of Nephilatoxin-8(NPTX-^*),a New Neurotoxin of Joro Spider (Nephila clavata)" Chemistry Letters. 929-932 (1993)
[Publications] M.Miyashita: "Enantioselective Synthesis of (-)-Serricornin,a Sex Pheromone of a Female Cigarette Beetle (LasiodermaserricomeF.)" Tetrahedron Asymmetry. 4. 1573-1578 (1993)
[Publications] S.Hatakeyama: "Enantiospecific Synthesis of (+)-Paeonilactone C nad (+)-Paeoniflorigenone from R-(-)-Carvone" Tetrahedron Lett.35. 7993-7996 (1994)
[Publications] S.Hatakeyama: "An Efficient Route to a Key A-Ring Synthon for 1,25-Dihydroxyvitamin D3 and its Analogs" Tetrahedron. 50. 13369-13376 (1994)
[Publications] S.Hatakeyama: "Total Synthesis of (+)-Paeonilactone B and (-)-Paeonisuffrone" Tetrahedron Lett,. 36. 267-268 (1995)
[Publications] M.Miyashita: "Total Synthesis of Nephilatoxin-7 (NPTX-7),a New Neurotoxin of Joro Spider (Nephila clavata)" Tetrahedron Lett. 36. 5231-5234 (1995)
[Publications] M.Miyashita: "An Efficient Synthesis of JSTX-3,a Potent Neurotoxin of Joro Spider (Nephila clavata)" Tetrahedron. 51. 10687-10698 (1995)
[Publications] S.Hashimoto: "Double Asymmetric Inductiom in Intramolecular C-H Insertion Reaction of α-Diazo β-Keto Esters" Synthetic Communications. 24. 3277-3287 (1994)
[Publications] N.Watanabe: "Asymmetric Creation of Quatemary Carbon Centers by Enantiotopically Selective Aromatic C-H Insertion Catalyzed by Chiral Dirhodium (II) Carboxylates" Tetrahedron Lett,. 36. 1491-1494 (1994)
[Publications] S.Hashimoto: "A New Access to Mori′s Intermediate for the Practical Synthesis of (-)-Periplanone-B" Chemistry Lett,. 1091-1092 (1995)
[Publications] M.Tokuda: "Synthesis of Hybrid Molecule Containing Neocarzinostatin Chromophore Analogue and Minor Groove Binder" Tetrahedron Letters. 34. 669-672 (1993)
[Publications] K.Takahasi: "Synthesis and Binding of Simple Neocarzinostatin Chromophore Analogues to the Apoprotain" Tetrahedron,Symposia in Print,. 50. 1327-1340 (1994)
[Publications] M.Yamaguchi: "Chemistry and Antimicrobial Activity of Caryoynencins Analogus" J.Med.Chem. 38. 5015-5022 (1995)
[Publications] S.Takano: "Concise Enantiodivergent Synthesis of Eutypoxide" J.Chem.Soc.,Chem.Commun.614-615 (1993)
[Publications] K.Samizu: "An Expedient Route to Indole-3-acetic Acid Derivatives" Synlett. 499-500 (1994)
[Publications] K.Shin: "A New Synthesis of the Naturally Occurring Free Radical Scavenger Carazostatin" Chem.Lett.289-290 (1995)
[Publications] K.Hiroi: "Palladium-catalyzed Intermolecular Asymmetric Metallo-Ene Reactions via Allylic Sulfinate-Sulfone Rearrangement" Chem.Pharm.Bull.42. 1036 (1995)
[Publications] H.Sasai: "The First Heterobimetallic Multifunctional Asymmetric Catalyst" J.Am.Chem.Soc.117. 6194-6198 (1995)
[Publications] T.Saito: "Total Synthesis of (±)-Furaquinocin D" J.Am.Chem.Soc.117. 10757-10758 (1995)
[Publications] T.Takahashi: "Synthesis of Dynemicin A Analogue and Its Bergman-Type Cycloaromatization" Angew.Chem.Int.Ed.Engl.34. 1345-1348 (1995)
[Publications] D.Uemura: "Pinnatoxin A : A Toxic Amphoteric macrocycle from Okinawa Bivalva Pinna Muricata" J.Am.Chem.Soc.117. 1155-1156 (1995)
[Publications] N.Sugimoto: "Mobility Inhibition and Nematocidal Activity of Asarone and Related Phenylpropanoids on Second-Stage Larvae of Toxocare canis" Biol.Pharm.Bull.18. 605-609 (1995)
[Publications] K.Fuji: "An Enantioselective Synthesis of (-)-Psudophrynaminol though Asymmetric Nitroolefination" Synlett,. 367 (1995)
[Publications] H.Tamamura: "Synthesis of Protegrin-Related Peptides and Their Antibacterial and Anti-Human Immunodeficiency Virus Activity" Chem.Pharm.Bull.43. 853-858 (1995)
[Publications] M.Kanai: "Asymmetric Conjugate Addition of Organomagnesium Cuprates Controlled by Stoichiometric Amount of Chiral Phosphine" Tetrahedron Lett,. 36. 4273-4274 (1995)
[Publications] T.Kan: "Internal Activation of Acrylate-type Dienophiles in Diels-Alder Reactions" Tetrahedron Lett,. 36. 943-946 (1995)
[Publications] S.Hatakeyama: "A Facile Stereoselective Route to a C/D-Ring Synthon for 20-Epi-2-oxavitamine D3 Analogues" J.Chem.Soc.,Chem.Commun.1959-1960 (1995)
[Publications] T.Sagara: "Specific Affinity Labeling of m Opioid Recepters in Rat Brain by S-Activated Sulfidyldihydromorphine Analogues" Bioorg.Med.Chem.Lett,. 5. 1609-1614 (1995)
[Publications] K.Fujita: "6-O-Sulfonates of Cycloinulohexaose (Cyclofructan-6)" Tetrahedron Lett.35. 2197-2200 (1994)
[Publications] K.Suga: "Prolidase from Xanthomonas maltophilia : Purification and Characterization of the Enzyme" Biosci.Biotech.Biochem.59. 2087-2090 (1995)

1995 Fiscal Year Annual Research Report

特異な生理活性を示す微量天然物の量的供給を志向した合成研究

Principal Investigator

入江 寛 長崎大学, 薬学部, 教授 (00025686)

Research Products

[Publications] M.Miyashita: "Total Synthesis of Nephilatoxin-8(NPTX-^*),a New Neurotoxin of Joro Spider (Nephila clavata)" Chemistry Letters. 929-932 (1993)

[Publications] M.Miyashita: "Enantioselective Synthesis of (-)-Serricornin,a Sex Pheromone of a Female Cigarette Beetle (LasiodermaserricomeF.)" Tetrahedron Asymmetry. 4. 1573-1578 (1993)

[Publications] S.Hatakeyama: "Enantiospecific Synthesis of (+)-Paeonilactone C nad (+)-Paeoniflorigenone from R-(-)-Carvone" Tetrahedron Lett.35. 7993-7996 (1994)

[Publications] S.Hatakeyama: "An Efficient Route to a Key A-Ring Synthon for 1,25-Dihydroxyvitamin D3 and its Analogs" Tetrahedron. 50. 13369-13376 (1994)

[Publications] S.Hatakeyama: "Total Synthesis of (+)-Paeonilactone B and (-)-Paeonisuffrone" Tetrahedron Lett,. 36. 267-268 (1995)

[Publications] M.Miyashita: "Total Synthesis of Nephilatoxin-7 (NPTX-7),a New Neurotoxin of Joro Spider (Nephila clavata)" Tetrahedron Lett. 36. 5231-5234 (1995)

[Publications] M.Miyashita: "An Efficient Synthesis of JSTX-3,a Potent Neurotoxin of Joro Spider (Nephila clavata)" Tetrahedron. 51. 10687-10698 (1995)

[Publications] S.Hashimoto: "Double Asymmetric Inductiom in Intramolecular C-H Insertion Reaction of α-Diazo β-Keto Esters" Synthetic Communications. 24. 3277-3287 (1994)

[Publications] N.Watanabe: "Asymmetric Creation of Quatemary Carbon Centers by Enantiotopically Selective Aromatic C-H Insertion Catalyzed by Chiral Dirhodium (II) Carboxylates" Tetrahedron Lett,. 36. 1491-1494 (1994)

[Publications] S.Hashimoto: "A New Access to Mori′s Intermediate for the Practical Synthesis of (-)-Periplanone-B" Chemistry Lett,. 1091-1092 (1995)

[Publications] M.Tokuda: "Synthesis of Hybrid Molecule Containing Neocarzinostatin Chromophore Analogue and Minor Groove Binder" Tetrahedron Letters. 34. 669-672 (1993)

[Publications] K.Takahasi: "Synthesis and Binding of Simple Neocarzinostatin Chromophore Analogues to the Apoprotain" Tetrahedron,Symposia in Print,. 50. 1327-1340 (1994)

[Publications] M.Yamaguchi: "Chemistry and Antimicrobial Activity of Caryoynencins Analogus" J.Med.Chem. 38. 5015-5022 (1995)

[Publications] S.Takano: "Concise Enantiodivergent Synthesis of Eutypoxide" J.Chem.Soc.,Chem.Commun.614-615 (1993)

[Publications] K.Samizu: "An Expedient Route to Indole-3-acetic Acid Derivatives" Synlett. 499-500 (1994)

[Publications] K.Shin: "A New Synthesis of the Naturally Occurring Free Radical Scavenger Carazostatin" Chem.Lett.289-290 (1995)

[Publications] K.Hiroi: "Palladium-catalyzed Intermolecular Asymmetric Metallo-Ene Reactions via Allylic Sulfinate-Sulfone Rearrangement" Chem.Pharm.Bull.42. 1036 (1995)

[Publications] H.Sasai: "The First Heterobimetallic Multifunctional Asymmetric Catalyst" J.Am.Chem.Soc.117. 6194-6198 (1995)

[Publications] T.Saito: "Total Synthesis of (±)-Furaquinocin D" J.Am.Chem.Soc.117. 10757-10758 (1995)

[Publications] T.Takahashi: "Synthesis of Dynemicin A Analogue and Its Bergman-Type Cycloaromatization" Angew.Chem.Int.Ed.Engl.34. 1345-1348 (1995)

[Publications] D.Uemura: "Pinnatoxin A : A Toxic Amphoteric macrocycle from Okinawa Bivalva Pinna Muricata" J.Am.Chem.Soc.117. 1155-1156 (1995)

[Publications] N.Sugimoto: "Mobility Inhibition and Nematocidal Activity of Asarone and Related Phenylpropanoids on Second-Stage Larvae of Toxocare canis" Biol.Pharm.Bull.18. 605-609 (1995)

[Publications] K.Fuji: "An Enantioselective Synthesis of (-)-Psudophrynaminol though Asymmetric Nitroolefination" Synlett,. 367 (1995)

[Publications] H.Tamamura: "Synthesis of Protegrin-Related Peptides and Their Antibacterial and Anti-Human Immunodeficiency Virus Activity" Chem.Pharm.Bull.43. 853-858 (1995)

[Publications] M.Kanai: "Asymmetric Conjugate Addition of Organomagnesium Cuprates Controlled by Stoichiometric Amount of Chiral Phosphine" Tetrahedron Lett,. 36. 4273-4274 (1995)

[Publications] T.Kan: "Internal Activation of Acrylate-type Dienophiles in Diels-Alder Reactions" Tetrahedron Lett,. 36. 943-946 (1995)

[Publications] S.Hatakeyama: "A Facile Stereoselective Route to a C/D-Ring Synthon for 20-Epi-2-oxavitamine D3 Analogues" J.Chem.Soc.,Chem.Commun.1959-1960 (1995)

[Publications] T.Sagara: "Specific Affinity Labeling of m Opioid Recepters in Rat Brain by S-Activated Sulfidyldihydromorphine Analogues" Bioorg.Med.Chem.Lett,. 5. 1609-1614 (1995)

[Publications] K.Fujita: "6-O-Sulfonates of Cycloinulohexaose (Cyclofructan-6)" Tetrahedron Lett.35. 2197-2200 (1994)

[Publications] K.Suga: "Prolidase from Xanthomonas maltophilia : Purification and Characterization of the Enzyme" Biosci.Biotech.Biochem.59. 2087-2090 (1995)

入江寛長崎大学, 薬学部, 教授 (00025686)