2006 Fiscal Year Final Research Report Summary
Remarkably Efficient Synthesis of Bioactive Compounds Using New Synthons
| Project/Area Number |
17550049
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Organic chemistry
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| Research Institution | Waseda University |
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Principal Investigator |
HOSOKAWA Seijiro Faculty of Science and Engineering, Assistant, Professor, 理工学術院, 講師 (10307712)
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| Project Period (FY) |
2005 – 2006
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| Keywords | remote stereoinduction / vinyl ketene N, O-acetal / natural product synthesis / total synthesis / bioactive natural product / multiple aromatic rings compound / synthon |
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| Research Abstract |
Short and efficient syntheses of some bioactive natural products have been achieved by our original methodologies. Linear chain polyketides including 5-lipoxygenase inhibitor lagunamycin, anti Hericobacter Pyroli antibiotic actinonpyrone A, and antitumor khafrefungin have been synthesized stereoselectively by means of our original remote stereoinduction methodologies, the reaction between aldehyde and ketene sily1-N, O-acetal possessing a chiral auxiliary in the presence of Lewis acid to construct γ-hydroxy-a, β-unsaturated imide. In the cases of lagunamycin and actinopyrone A the first syntheses were achieved, and both syntheses took only nine steps in the longest linear sequence. These syntheses are remarkably short and highly stereoselective. Additionally, by these syntheses the absolute configurations of actinopyrone and lagunamycin were determined. Multiple aromatic rings compounds including semaphorin-3A inhibitor vinaxanthone and endotheline converting enzyme inhibitor TMC-66 ha
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ve also been synthesized. Both of them are the first total syntheses. In the total synthesis of vinaxanthone, biogenetical intermediary was assumed and synthesized to reduce the synthetic sequence. The efficient total synthesis of vinaxanthone was accomplished with the intermediary. TMC-66, the sequential seven rings having two chiral centers, was synthesized by coupling two parts, both having three rings, at the center and successive intramolecular oxidative coupling. This strategy lead to the efficient total synthesis, which included 9 steps in the longest linear sequence and was accomplished to determine the absolute configuration of TMC-66.
Thus, synthetic studies on bioactive natural products including linear chain polyketides and multiple aromatic rings compounds have been promoted successively by this financial aid. Methodologies applied to these total syntheses are very powerful to make bioactive compounds in short steps. The results of these studies made stereoselective synthesis of medium size compounds possessing molecular weight 300~550 easy to get in a short term with simple handling.
Studies on new chemistries developed through these total syntheses are in progress. Less
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