Synthetic study of novel inositol phosphoceramide CJP2
| Project/Area Number |
15590006
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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 | NARA INSTITUTE OF SCIENCE AND TECHNOLOGY |
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Principal Investigator |
SHIRAI Ryuichi Nara Institute of Science and Technology, Research and Education Center for Materials Science, Associate Professor, 物質科学教育研究センター, 助教授 (80183838)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | ganglioside / CJP2 / sialic acid / inositol / ceramide / stereoselective synthesis / asymmetric synthesis / total synthesis |
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| Research Abstract |
The novel type ganglioside CJP2 has been obtained by Higuchi and co-workers from the feather star Comanthus japonica. This ganglioside is unique in that it is an inositolphosphoceramide derivative possessing sialic acid ; such ganglioside has not previously been identified. The presence of 9-O-methyl-N-glycolylneuraminosyl residue is also unique in naturally occurring gangliosides. Inositol phosphoceramide (IPC) is present in quite considerable quantities in higher plants, yeast, fungi, some bacterial cultures and mutant yeasts. Though their endogeinc functions are not well understood, but they are believed to protect plant tissues from necrotic lesions and are supposed to be applicable as test for the diagnosis of histoplasmosis. Because of limited availability of CJP2, their biological activity remains unknown. Development of the sufficient synthetic method to supply this class of compounds was investigated by stereoselective total synthesis from D-glucose. The synthesis of myo-inositol fragment of IPC is characterized by diastereoselective 1,2-addition of vinyl copper reagent to the chiral aldehyde derived from D-glucose, Wittig metbylenation, Ring-closing metathesis (RCM) of 1,7-diene and catalytic diastereoselective OsO4 dihydroXylation. The ceramide fragment was synthesized according to the modified procedure of Ogawa's method. The glycal fragment of sialc acid derivative as the useful precursor of glycosyl donor of sialic acid was also synthesized from D-glucose. The key step of this synthesis is the direct formation of unsaturated glycal moiety by RCM of 1,7-diene to produce sialic acid glycal derivative. The present synthesis provided myo-inositol fragment, ceramide fragment and sialic acid glycal fragment of CJP2. Further functional group transformation and coupling of these fragments will provide CJP2 and its related analogs valuable for biological evaluations.
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Report
(3 results)
Research Products
(4 results)
