1998 Fiscal Year Final Research Report Summary
Synthetic Studies on Protein Phosphatase Inhibitor Dysidiolide
| Project/Area Number |
09672165
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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 | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
YAMADA Yasuji Tokyo University of Pharmacy and Life Science, School of Pharmacy, Professor, 薬学部, 教授 (10057317)
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| Project Period (FY) |
1997 – 1998
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| Keywords | dysidiolide / synthesis / Diels-Alder reaction / protein phosphatase cdc25A / protein phosphatase inhibitor / sponge / lipase |
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| Research Abstract |
Dysidiolide, a novel sesterterpenoid isolated from the Caribbean sponge Dysidia eiheria de Laubenfels, exhibits inhibition of the protein phosphatase cdc25A.Dysidiolide possesses a unique carbon skeleton with structural features that find no precedent in nature. Thus, its unique structure and biological activity prompted me to undertake the synthetic studies of dysidiolide. I have achieved following three heading in this study.
1. Exploitation of Synthetic Method for Decalin Part of Dysidiolide using Intramolecura Diels-Alder Reaction
I developed synthetic method for decalin part of dysidiolide using model compound. This synthesis involves preparation of alpha, beta-unsaturated lactone by intramolecura Diels-Alder reaction, stereoselective methylation by Me_2CuLi at C-6 position and stereoselective alkylation at C-7 position.
2. Formal Synthesis of (*)-Dysidiolide
Decalin part of dysidiolide was synthesized according to above method. Deoxyganation of the C-12 and C-24 positions and extension of side chain completed the formal synthesis of (*)-dysidiolide.
3. Synthesis of Optically Active Cyclohexene Derivative Using Lipase
Optically active cyclohexene derivative was synthesized by optical resolution using Lipase AK.This compound is useful for the synthesis of optically active dysidiolide as a starting material.
The synthesis of optically active dysidiolide is now in progress.
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