| Project/Area Number |
06453172
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Bioproduction chemistry/Bioorganic chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
ICHIKAWA Yoshiyasu Nagoya University, School of Agricultural Sciences, Associate Professor, 農学部, 助教授 (60193439)
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| Co-Investigator(Kenkyū-buntansha) |
OHTANI Ikuko Nagoya University, School of Agricultural Sciences, Research Associate, 農学部, 助手 (40247680)
NISHIKAWA Toshio Nagoya University, School of Agricultural Sciences, Research Associate, 農学部, 助手 (90208158)
ISOBE Minoru Nagoya University, School of Agricultural Sciences, Professor, 農学部, 教授 (00023466)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1994: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | Protein Phosphatase / Inhibitor / Tautomycin / Organinc Synthesis / 阻害剤 / 蛋白脱リン酸化酵素阻害剤 / 立体制御合成 / 分子力場計算 / 立体配座解析 / 活性発現機構 |
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| Research Abstract |
1) Degradation product including the moiety for C-19 through to C-25 of tautomycin were synthesized. This synthesis confirmed the relative stereochemistry at C-23 and C-24 of tautomycin.
2) We have accomplished the stereoselective synthesis of three segments A,B,C which were derived by retrosynthetic analysis of tautomycin.
3) Segment B/C corresponding to the C26 through to the C1 positions of tautomycin was synthesized by the reaction of epoxide with sulfone carbanion in the presence of boron trifluoride etherate. Conpling reaction of Segment A and Segment B/C was achieved by modified Yamaguchi esterification method. Transformation of the furan ring into the maleic anhydride and removal of the protecting groups completed the total synthesis of tautomycin.
4) The stereochemistry of tautomycin in solution has been confirmed by employing molecular mechanistic calculation and high-field NMR technique.
5) The crucial functionality of tautomycin for the inhibitory activity has been determined by measuring the activity of the of tautomycin derivatives prepared by chemical synthesis.
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