1997 Fiscal Year Final Research Report Summary
Chemical Studies of alpha-Pyrone Meroterpenoids
| Project/Area Number |
08672444
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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 |
Chemical pharmacy
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| Research Institution | Kitasato University |
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Principal Investigator |
SUNAZUKA Toshiaki Kitasato University, 薬学部, 講師 (30226592)
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| Co-Investigator(Kenkyū-buntansha) |
OMURA Satoshi The Kitasato Institute, 所長 (90050426)
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| Project Period (FY) |
1996 – 1997
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| Keywords | alpha-Pyrone / Meroterpenoid / ACAT / Total Synthesis / Coupling reaction / sesquiterpene / biomimetic / Structure-Activity Relationships |
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| Research Abstract |
The first total synthesis of the microbial a-pyrone meroterpenoid, (+)-pyripyropene A (1), acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor, which is effective and concise convergent approach (14 steps, 9.3% yield), designed to afford easy access to both the natural products and a variety of analogs, has been achieved. The key step is the coupling reaction between a-pyrone-pyridine moiety (4) and the acid chloride of sesquiterpene moiety (3) in the presence of Lewis acid to construct ketone (2). The sesquiterpene moiety has been synthesized via stereoselective reductive formylation, palladium associated carbonylation, and allylic oxidation started from (+)-Wieland-Wiescher ketone.
(+)-Pyripyropene E (15) also has been synthesized from farnesyl acetate
(9 steps, 9.6 % overall yield). The convergent and stereoselective route exploited a biomimetic polyene cyclization as the key transformation.
We also made over 300 derivatives usuing theses synthetis scheme, and clarified the structure-activity relationships.
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