New Frontier in Bioorganic Chemistry Research

1989 Fiscal Year Final Research Report Summary

• Project/Area Number: 62303017
• Research Category: Grant-in-Aid for Co-operative Research (A)
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: Kyoto University
• Principal Investigator: YONEDA Fumio Faculty of Pharmaceutical Sciences, Kyoto Univ., 薬学部, 教授 (80040327)
• Co-Investigator(Kenkyū-buntansha): FUJII Nobutaka Faculty of Pharmaceutical Sciences, Kyoto Univ. Professor., 薬学部, 教授 (60109014) ; HIROBE Masaaki Faculty of Pharmaceutical Sciences, Tokyo Univ. Professor., 薬学部, 教授 (20012594) ; FUJITA Tetsuro Faculty of Pharmaceutical Sciences, Kyoto Univ. Professor., 薬学部, 教授 (40027024) ; OHTSUKA Eiko Faculty of Pharmaceutical Sciences, Hokkaido Univ. Professor., 薬学部, 教授 (80028836) ; UEDA Tooru Faculty of Pharmaceutical Sciences, Hokkaido Univ. Professor., 薬学部, 教授 (00001032)
• Project Period (FY): 1987 – 1989
• Keywords: Chiral 5-deazaflavin / Retinoid / P-450 model / Modified oligonucleotide / Chiral synthesis / Peptide synthesis / Opioid receptor / Esperamicin

Research Abstract

New frontiers in bioorganic chemistry focused on nucleic acid, enzyme and bioactive compounds including coenzyme have been developed as follows: 1) Redox coenzyme Factor 420, which was isolated from methane-producing bacteria, has first been synthesized. An axial and planar chiral 5-deazaflavin coenzyme model was designed and synthesized (F. Yoneda). 2) Several oligodeoxyribonucleotides containing 5-modified uracils were synthesized and their interactions with restriction endonuleases were investigated,(T. Ueda). 3) Several oligoribonuleotides have been synthesized using 5'-levulinyl and 2'-tetrahydrofuranyl protection and the phophoramidite approach(E. Ohtsuka). 4) Structure-activity relationships of retinoids were clarified and a new type of retinoidal compounds have been synthesized (K. Shudo). 5) Cytochrome P-450 model system has been constructed and its molecular mechanism has been elucidated (M. Hirobe). 6) Large ring lactone-epoxides possessing ionophore activity were prepared and furthermore naturally occurring ionophores from natural sources have been searched (I. Kitagawa). 7) New reaction mechanism of opioid receptor has been explained using synthetic ligands with active disulfide substituents (K. Kanematsu). 8) Trichosprin-B has been isolated from Trichoderma polysporum and its structure has been determined. The total synthesis also has been achieved (T. Fujita). 9) Several new deprotection methodologies and new disulfide formation reactions have been developed (N. Fum). 10) Synthesis of chiral lactones through addition-elimination process has been realized and its application to indole alkaloids has been achieved (K. Fuji). 11) Nucleotide-specific cleavage and minor-groove interaction of DNA with antitumor antibiotics, bleomycin and esperamicin (Y. Shigiura).

Research Products

• [Publications] Fumio Yoneda: "Synthesis of Bis(pyridodipyrimidines)an Autorecycling Redox Catalysts and Their Remarkable Turonover in the Oxidation of Alcohols" J.Am.Chem.Soc. 111. 9199-9202 (1989)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tetsuji Kawamoto: "Synthesis and Reaction of a New Type of 5ーDeazaflavin with Axial and Planar Chirality" Tetrahedron Letters. 30. 7431-7434 (1989)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Jun Takeda: "Synthesis and Characterization of Novel FlavinーLinked Porphyrins.Mechanism for FlavinーCatalysed Interand Intramolecular 2e/1e ElectronーTransfer Reactions" J.Am.Chem.Soc.109. 7677-7688 (1987)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kaour Fuji: "Direct Asymmetric Synthesis of Quaternary Carbon Centers via AdditionーElimination Process:Nitroolefination of αーSubstitueted δーLactones" J.Am.Chem.Soc.111. 7921-7925 (1989)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yukio Sugiura: "Nucleotideーspecific Cleavage and Minorーgroove Interaction of DNA with Esperamicin Antitumor Antibiotics" Proc.Natl.Acad.Sci.USA. 86. 7672-7676 (1989)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] June Kuwahara: "Sequenceーspecific Recognition and Cleavage of DNA by Metallobleomycin:Minor Groove Binding and Possible Interaction Mode" Proc.Natl.Acad.Sci.USA. 85. 2459-2463 (1988)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fumio Yoneda et al.: "Synthesis of Bis(pyridodipyrimidines) as Autorecycling Redox Catalysts and Their Remarkable Turnover in the Oxidation of Alcohols." J. Am. Chem. Soc.111. 9199-9202 ((1989))
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Jun Takeda et al.: "Synthesis and Characterization of Novel Flavin-Linked Porphyrins. Mechanism for Flavin-Catalysed Inter- and Intramolecular 2e/1e Electron-Transfer Reactions." J. Am. Chem. Soc., 109, 7677-7688 (1987).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kaoru Fuji et al.: "Direct Asymmetric Synthesis Quaternary Carbon Centers via Addition-Elimination Process: Nitroolefination of alpha-Substituted delta-Lactones." J. Am. Chem. Soc., 111, 7921-7925 (1989).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yukio Sugiura et al.: "Nucleotide-specific Cleavage and Minor-Groove Interaction of DNA with Esperamicin Antitumor Antibiotics." Proc. Natl. Acad. Sci. USA, 86, 7672-7676 (1989).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] "Sequence-Specific Recognition and Cleavage of DNA by Metallobleomycin: Minor Groove Binding and Possible Interaction Mode." Proc. Natl. Acad. Aci. USA, 85, 2459-2463 (1989).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] "Synthesis and Reaction of a New Type of 5-Deazaflavin with Axial and Planar Chirality" Tetrahedron Letters 30, 7431-7434 (1989).
  • Description: 「研究成果報告書概要(欧文)」より