Synthetic Studies on Protein Phosphatase Inhibitor Dysidiolide
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Tokyo University of Pharmacy and Life Science|
YAMADA Yasuji Tokyo University of Pharmacy and Life Science, School of Pharmacy, Professor, 薬学部, 教授 (10057317)
|Project Period (FY)
1997 – 1998
Completed(Fiscal Year 1998)
|Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 1998 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1997 : ¥1,800,000 (Direct Cost : ¥1,800,000)
|Keywords||dysidiolide / synthesis / Diels-Alder reaction / protein phosphatase cdc25A / protein phosphatase inhibitor / sponge / lipase / プロテインホスファターゼ阻害 / cdc25A|
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.
Research Output (2results)