1994 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	Nagasaki 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(新規メンバー)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が、その成果は本研究の最終年度に提出する成果報告書にまとめる予定である。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
(26 results)

All Other

All Publications (26 results)

[Publications] Maruyama,M.Kobayashi,M.Miyashita,I.Kouno,and H.lrie: "A Synthesis of(±)-Pinoresinol and its Related Compound using Potassium Persulfate (K_2S_2O_8)Oxidation of Banzoylacetates" Heyerocyles,. 37. 839-845 (1994)
[Publications] H.Kuroda,M.Miyashita,H.Irie,and T.Ueno: "Studies of the Structure-Toxicity Relatioship of AK-Toxin,a Host Specific Toxin to Japanese White Pear,Produced by Alternaris kikuchiana:Synthesis of Methyl(4S,5R)-4-(N-Acetylphenylalanyl)oxy-5,6-epoxy-5-methylhex-2(E)-enoate and its Stereoisomers" Chem.Pharm.Bull.,. 42. 1328-1330 (1994)
[Publications] S.Hatakeyama,M.Kawamura,S.Takano,and H.Irie: "Enantiospecific Synthesis of (+)-Paeonilactone C and(+)-Paeoniflorigenone from(R)-(-)-Carvone" Tetrahedron Letters. 35. 7993-7996 (1994)
[Publications] H.Irie,et al.: "An Efficient Rourte to a Key A-Ring Synthon for 1a,25-Dihydroxyvitamin D_3and its Analogs" Tetrahedron,. 50. 13369-13376 (1994)
[Publications] H.Irie,et al.: "Total Synthesis of(+)-Paeonisuffrone" Tetrahedron Letters,. 36. 267-268 (1995)
[Publications] N.Fujii,K.Makai,H.Habashita,Y.Hotta,H.Tamamura,A.Otaka,: "Synthesis of Optically Pure 2-Aziridinemethanols:Versatile Synthetic Building Blocks" Chem.Pharm.Bull.,. 42. 2241-2250 (1994)
[Publications] N.Fujii,et al.: "A novel Route to Diastereomerically Pure(E)-Alkene Dipeptide Isosteres from b-Aziridinyl-a,b-enoates by Treatment with Organocopper Reagents" Angew.Chem.Int.Ed.Engl.33. 652-654 (1994)
[Publications] D.Uemura,et al.: "Pinnatoxin A:A toxic Amephoteric Macrocycle from the Okinawa Bivalve Pinna muricata" J.Amer.Chem.Soc.117. 1155-1156 (1995)
[Publications] D.Uemura,et al.: "Stimulation of Nerve Growth Factor Production by Diterpenoids Isolated from Plants of Euphorbia Species." Biosic.Biotech.Biochem.58. 1749-1751 (1994)
[Publications] Y.Tsuda,et al.: "Chiral Synthesis of Erythrina Alkaloids.(2).Synthesis of enantio-Type Erythrinan Alkaloids Utilizing Asymmetric Acylation and Kinetic Resolution of Diastereomers" Chem.Pharm.Bull.42. 204-213 (1994)
[Publications] K.Hiroi,et al.: "The Palladium-Catalyzed Asymmetric a-Allylations of Carbonyl Compounds with Chiral Allyl Estsrs via Enamines and Imines" J.Org.Chem.59. 203-213 (1994)
[Publications] K.Hiroi,et al.: "Transition Metal-Catalyzed Asymmetric Vinylcyclopropane-Cyclopentene Rearrangements.Asymmetric Synthesis of Cyclopentene Derivatives Using Chiral Sulfoxides as Chiral Sources" Tetrahedron Lett.35. 153-156 (1994)
[Publications] Y.Ohfune,et al.: "Synthesis and Neurobiological Actions of Pyrrolidine-2,3-dicarboxylic Acids(PRDA).Conformationally Restricted Analogues of L-Aspartate" Bioorg.Med.Chem.Lett.4. 1851-1854 (1994)
[Publications] Y.Ohfune,et al.: "Efficient Syntheses of the Four Enantiomers and Diastereomers of a-Methylthreonine and Both Enantiomers of a-Methylserine" J.Amer.Chem.Soc.116. 7405-7406 (1994)
[Publications] K.Ogasawara,et al.: "Enantioconvergent Preparation of the A-Ring Precursors of Calcitriol from Either(R)-or(S)-Epichiorohydrin" J.Chem.Soc.,Chem.Commun.1994. 1903-1904 (1994)
[Publications] K.Ogasawara,et al.,: "Enantioconvergent Route to a Functionalzed Quinane System" Synthesis,. 1029-1094 (1994)
[Publications] K.Suzuki,: "Total Synthesis of Aryl-Glycoside Antibiotics" Pure Appl.Chem.66. 2175-2178 (1994)
[Publications] T.Hosoya,E.Takashiro,T.Matsumoto,and K.Suzuki,: "First Total Synthesis of BE-12406A" Tetrahedron Lett.35. 4591-4594 (1994)
[Publications] S.Nakamura and M.Shibasaki: "Synthetic Studies on Taotomycin.Stereoselective Construction of the C_1-C_<26> Region" Tetrahedron Lett.35. 4145-4148 (1994)
[Publications] M.Shibasaki,et al.: "Effects of Solvents and Additives in the Asymmetric Heck Reaction of Alkenyl Triflates:Catalytic Asymmetric Synthesis of Decalin Derivatives nad Determination of the Absolute Stereochemistry of(+)-Vernolepi" J.Am.Chem.Soc.116. 11737-11748 (1994)
[Publications] D.M.Garcia,HY.Yamada,S.Hatakeyama,and M.Nishizawa: "Total Synthesis of Arthrobaclilin A" Tetrahedron Lett.35. 3325-3328 (1994)
[Publications] M.Nishizawa,R.Minagawa,D.M.Garcis,S.Hatakeyama: "Syntheses and Characterzation of Four Diasteremers of Trehalose-6,6'-Dicorynomycolates(TD BH32)" Tetrahedron Lett.35. 5891-5894 (1994)
[Publications] T.Suzuki,and M.Hirama: "Synthesis and Binding of Simple Neucarzinostatin Chromophore Analogues to the Apoprotein" Tetrahedron,Symposia in Print,. 50. 1327-1340 (1994)
[Publications] K.Iida and M.Hirama: "Effcient Route to the 9-Membered Cyclic Diyne System:Tuning of the Extremely Facil Cope Rearrangement of 1,5-Diyne" J.Am.Chem.Soc.116. 10310-10311 (1994)
[Publications] A.Ojima,F.Tanoue,and K.Kanemastu: "Total Syntheses of Marine Furanosesquiterpenoids,Tubipofurans" J.Org.Chem.59. 5970-5976 (1994)
[Publications] S.Nagashima,T.Taishi,and K.Kanematsu: "Access to an Optically Pure Key Intermediate of Dihydromevinolin" Tetrahedron Lett.35. 3577-3580 (1994)

1994 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] Maruyama,M.Kobayashi,M.Miyashita,I.Kouno,and H.lrie: "A Synthesis of(±)-Pinoresinol and its Related Compound using Potassium Persulfate (K_2S_2O_8)Oxidation of Banzoylacetates" Heyerocyles,. 37. 839-845 (1994)

[Publications] S.Hatakeyama,M.Kawamura,S.Takano,and H.Irie: "Enantiospecific Synthesis of (+)-Paeonilactone C and(+)-Paeoniflorigenone from(R)-(-)-Carvone" Tetrahedron Letters. 35. 7993-7996 (1994)

[Publications] H.Irie,et al.: "An Efficient Rourte to a Key A-Ring Synthon for 1a,25-Dihydroxyvitamin D_3and its Analogs" Tetrahedron,. 50. 13369-13376 (1994)

[Publications] H.Irie,et al.: "Total Synthesis of(+)-Paeonisuffrone" Tetrahedron Letters,. 36. 267-268 (1995)

[Publications] N.Fujii,K.Makai,H.Habashita,Y.Hotta,H.Tamamura,A.Otaka,: "Synthesis of Optically Pure 2-Aziridinemethanols:Versatile Synthetic Building Blocks" Chem.Pharm.Bull.,. 42. 2241-2250 (1994)

[Publications] N.Fujii,et al.: "A novel Route to Diastereomerically Pure(E)-Alkene Dipeptide Isosteres from b-Aziridinyl-a,b-enoates by Treatment with Organocopper Reagents" Angew.Chem.Int.Ed.Engl.33. 652-654 (1994)

[Publications] D.Uemura,et al.: "Pinnatoxin A:A toxic Amephoteric Macrocycle from the Okinawa Bivalve Pinna muricata" J.Amer.Chem.Soc.117. 1155-1156 (1995)

[Publications] D.Uemura,et al.: "Stimulation of Nerve Growth Factor Production by Diterpenoids Isolated from Plants of Euphorbia Species." Biosic.Biotech.Biochem.58. 1749-1751 (1994)

[Publications] Y.Tsuda,et al.: "Chiral Synthesis of Erythrina Alkaloids.(2).Synthesis of enantio-Type Erythrinan Alkaloids Utilizing Asymmetric Acylation and Kinetic Resolution of Diastereomers" Chem.Pharm.Bull.42. 204-213 (1994)

[Publications] K.Hiroi,et al.: "The Palladium-Catalyzed Asymmetric a-Allylations of Carbonyl Compounds with Chiral Allyl Estsrs via Enamines and Imines" J.Org.Chem.59. 203-213 (1994)

[Publications] K.Hiroi,et al.: "Transition Metal-Catalyzed Asymmetric Vinylcyclopropane-Cyclopentene Rearrangements.Asymmetric Synthesis of Cyclopentene Derivatives Using Chiral Sulfoxides as Chiral Sources" Tetrahedron Lett.35. 153-156 (1994)

[Publications] Y.Ohfune,et al.: "Synthesis and Neurobiological Actions of Pyrrolidine-2,3-dicarboxylic Acids(PRDA).Conformationally Restricted Analogues of L-Aspartate" Bioorg.Med.Chem.Lett.4. 1851-1854 (1994)

[Publications] Y.Ohfune,et al.: "Efficient Syntheses of the Four Enantiomers and Diastereomers of a-Methylthreonine and Both Enantiomers of a-Methylserine" J.Amer.Chem.Soc.116. 7405-7406 (1994)

[Publications] K.Ogasawara,et al.: "Enantioconvergent Preparation of the A-Ring Precursors of Calcitriol from Either(R)-or(S)-Epichiorohydrin" J.Chem.Soc.,Chem.Commun.1994. 1903-1904 (1994)

[Publications] K.Ogasawara,et al.,: "Enantioconvergent Route to a Functionalzed Quinane System" Synthesis,. 1029-1094 (1994)

[Publications] K.Suzuki,: "Total Synthesis of Aryl-Glycoside Antibiotics" Pure Appl.Chem.66. 2175-2178 (1994)

[Publications] T.Hosoya,E.Takashiro,T.Matsumoto,and K.Suzuki,: "First Total Synthesis of BE-12406A" Tetrahedron Lett.35. 4591-4594 (1994)

[Publications] S.Nakamura and M.Shibasaki: "Synthetic Studies on Taotomycin.Stereoselective Construction of the C_1-C_<26> Region" Tetrahedron Lett.35. 4145-4148 (1994)

[Publications] M.Shibasaki,et al.: "Effects of Solvents and Additives in the Asymmetric Heck Reaction of Alkenyl Triflates:Catalytic Asymmetric Synthesis of Decalin Derivatives nad Determination of the Absolute Stereochemistry of(+)-Vernolepi" J.Am.Chem.Soc.116. 11737-11748 (1994)

[Publications] D.M.Garcia,HY.Yamada,S.Hatakeyama,and M.Nishizawa: "Total Synthesis of Arthrobaclilin A" Tetrahedron Lett.35. 3325-3328 (1994)

[Publications] M.Nishizawa,R.Minagawa,D.M.Garcis,S.Hatakeyama: "Syntheses and Characterzation of Four Diasteremers of Trehalose-6,6'-Dicorynomycolates(TD BH32)" Tetrahedron Lett.35. 5891-5894 (1994)

[Publications] T.Suzuki,and M.Hirama: "Synthesis and Binding of Simple Neucarzinostatin Chromophore Analogues to the Apoprotein" Tetrahedron,Symposia in Print,. 50. 1327-1340 (1994)

[Publications] K.Iida and M.Hirama: "Effcient Route to the 9-Membered Cyclic Diyne System:Tuning of the Extremely Facil Cope Rearrangement of 1,5-Diyne" J.Am.Chem.Soc.116. 10310-10311 (1994)

[Publications] A.Ojima,F.Tanoue,and K.Kanemastu: "Total Syntheses of Marine Furanosesquiterpenoids,Tubipofurans" J.Org.Chem.59. 5970-5976 (1994)

[Publications] S.Nagashima,T.Taishi,and K.Kanematsu: "Access to an Optically Pure Key Intermediate of Dihydromevinolin" Tetrahedron Lett.35. 3577-3580 (1994)

入江寛長崎大学, 薬学部, 教授 (00025686)