1999 Fiscal Year Final Research Report Summary
Asymmetric total synthesis of a novel tumor promoter
| Project/Area Number |
10672087
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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 |
医薬分子機能学
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| Research Institution | Kyoto University |
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Principal Investigator |
IIDA Akira Kyoto University, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (40202816)
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| Project Period (FY) |
1998 – 1999
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| Keywords | tumor promoter / trichothecene / trichothecinol / imperfect fungi / asymmmetric synthesis / olefin metathesis / Trichothecium roseum / bioactive natural product |
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| Research Abstract |
Novel trichothecenes, trichothecinol A, B and C isolated from Trichothecium roseum, acts as strong tumor promoters. Their mode of action in tumor promotion is different from those of other known tumor promoters, suggesting the presence of unknown mechanisms on carcinogenesis. In this project, an efficient synthetic route of trichithecenes has been developed in order to investigate biological properties of trichothecinols.
There are two important steps in the present synthetic strategy for trichothecenes. One is a stereoselective introduction of a methyl group into the chiral butenolide derived from D-mannitol in the early stage of the synthesis. The other is a construction of the cis A/B ring via the steric inversion at the γ-position of the lactone. According to the synthetic scheme, the first key intermediate was stereoselectively prepared from the chiral butenolide, followed by the steric inversion and ring closing olefin metathesis to afford the desired spirolactone in high chemical yield. Reductive opening of the lactone moiety, protection, oxidation and methylation gave the tertiary alcohol that is a intermediate before ring closing to the cis A/B ring. One flask reaction by acidic treatment of the alcohol yielded the ring closing product that has desired ring juncture for the cis A/B ring in good yield. Several steps led to an authentic compound reported by the Kraus group.
In conclusion, a formal total synthesis of trichothecene was enantioselectively done in high yield using D-mannitol as the starting material. Ring closing olefin metathesiswas a very useful method for the construction of the spirolactone, one of the most important key intermediate in the synthetic route.
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Research Products
(2 results)
