2007 Fiscal Year Final Research Report Summary
Development of a Novel Asymmetric Heck Reaction based on Dynamic Kinetic Resolution and Its Application
| Project/Area Number |
18590022
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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 | Kyoto Pharmaceutical University |
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Principal Investigator |
NODE Manabu Kyoto Pharmaceutical University, 薬学部, Professor (60027076)
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| Project Period (FY) |
2006 – 2007
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| Keywords | asymmetric Heck reaction / atropisomer / dynamic kinetic resolution / standishinal analogs / dichroanal B / dichroanone / taiwaniaauinone H / inhibitory activity against aromatase |
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| Research Abstract |
We have investigated a novel intramolecular asymmetric Heck reaction by use of the substrate having atropisomers. As the results, we could established a new type of asymmetric Heck reaction based on dynamic kinetic resolution through equilibration of atropisomers, which proceeded smoothly in high temperature to give the coupling product in high yields and in high enantiomeric excess.
As application of the Heck reaction, we designed asymmetric total syntheses of standishinal and its analogs having 4a-methyltetrahydrofluorene skeleton, which showed potent inhibitory activity against aromatase. Namely, standishinal analogs possessing the same skeleton such as dichroanone, dichroanals, and taiwaniaquinones, are expected to have promising activities as medicines for female hormone-dependent cancers. In conclusion, we succeeded in the asymmetric total syntheses of naturally occurring diterpenes having 4a-methyltetrahydrofluorene, i.e., (-)-dichroanal B, (-)-dichroanone, and (-)-taiwaniaquinone H.
On the other hand, asymmetric synthesis of (-)-standishinal having trans fused 5,6-membered ring system was very difficult. Therefore, dl-standishinal was synthesized by the use of aldol type bond formation of dialdehyde intermediate instead of above Heck reaction. We found more active compound than standishinal by the structure-activity relationship of inhibitory activity against aromatase using synthesized standishinal and its related compounds.
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