2001 Fiscal Year Final Research Report Summary
Search for and synthesis of anti-senile compound from marine organism.
| Project/Area Number |
11470473
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
YASUJI Yamada Tokyo University of Pharmacy and Life Science, School of Pharmacy, Professor., 薬学部, 教授 (10057317)
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| Co-Investigator(Kenkyū-buntansha) |
ASAKO SHIMOMURA Tokyo University of Pharmacy and Life Science, School of Pharmacy, Research Associate, 薬学部, 助手 (90277260)
HIDEMICHI Mitome Tokyo University of Pharmacy and Life Science, School of Pharmacy, Research Associate, 薬学部, 助手 (00266892)
SIROAKI MIYAOKA Tokyo University of Pharmacy and Life Science, School of Pharmacy, Associate Professor, 薬学部, 助教授 (10231622)
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| Project Period (FY) |
1999 – 2001
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| Keywords | stolomdiol / synthesis / choline acetvltransferase / cholinersic neuron / activater / soft coral / sponge / sequential Michael reaction |
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| Research Abstract |
Cholinergic neurons in the basal forebrain innervate the cortex and hippocampus, and their function may be closely related to cognitive function and memory. The degeneration of neuronal cells in this area is considered to be responsible for several types of dementia including Alzheimer's disease. Therefore, induction of choline acetyltransferase (ChAT) activity in cholinergic neurons may improve the cognitive function in diseases exhibiting cholinergic deficits such as Alzheimer's disease. We have achieved following two heading in this study.
1.Induction of ChAT Activity in Cholinergic Neurons by Marine Diterpenoid Stolonidiol
The effect of Stolonidiol, a bioactive marine diterpenoid. from Okinawan soft coral Clavularia sp., on ChAT activity was examined using cultured cholinergic neurons. Stolonidiol showed potent ChAT inducible activity in primary cultured basal forebrain cells and clonal septal SN49 cells, suggesting that it may act as a potent neurotrophic factor-like agent on the ch
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olinergic nervous system. Further expansion of the structure-activity relationship to include Stolonidiol and its derivatives demonstrated that the exo-methylene group and epoxide group are essential for ChAT-inducing activity. Stolonidiol showed the highest activity among the test samples.
Structurally unique new sesquiterpenoid quinones dactyloquinones A-F and their relative compounds dactylolactones A-D were isolated from an Okinawan sponge Dactylospongia elegans. Their structures were determined by spectroscopic analysis.
2.Total Synthesis of Marine Diterpenoid Stolonidiol
The total synthesis of marine dolabellane diterpenoid Stolonidiol was achieved from L-ascorbic acid. The method of total synthesis involves formation of the bicyclo[2.2.1]heptane derivative using diastereoselective sequential Michael reaction of cyclopentanone derivative and optically active a, p-unsaturated ester, formation of cyclopentane derivative by the retro-aldol reaction and construction of an 11-membered carbocyclic ring through the intramolecure Horner Wadsworth-Emmons reaction. " Less
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