2002 Fiscal Year Final Research Report Summary
Total synthesis of phosphatidylinositol 3,5-bisphosphate
| Project/Area Number |
13672215
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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) |
2001 – 2002
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| Keywords | PI 3,5-P2 / phosphatidylinositol / second messenger / intracellular signal transduction / asymmetric synthesis / total synthesis / stereoselective synthesis / glucose |
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| Research Abstract |
Phosphorylated phoshoinositides play pivotal roles as second messengers in intracellular signal transduction. Phosphatidylinositol 3,5-bisphosphate (PI 3,5-P2) was recently identified as novel second messenger. In this research project, phosphatidylinositol 3,5-bisphospate was synthesized by two different synthetic tactics. The first was diastereoselective synthesis from D-glucose, and the second was asymmetric desymmetrization of meso-myo-inositol derivative
1. Asymmetric total synthesis of phosphatidylinositol 3,5-bisphosphate from D-glucose
The 1,2-addition of vinyl copper reagent to the chiral aldehyde derivative fron D-glucose gave the desired diastereomer of allyl alcohol. Protection of hydroxyl group, acid hydrolysis, Wittig methylenation and ring-closing metathesis (RCM) gave the conduritol B derivatives. By catalytic OsO_4 oxidation of non-C_2 symmetric conduritol B derivatives, we could synthesize the desired diol as key intermediate of phosphatidylinositol 3,5-bisphosphate. Finally, this diol was successfully converted to phosphatidylinositol 3,5-bisphosphate by established amidite procedure
2. Enantioselective desymmetrization of meso-1,2,3-Triol
We could developed the highly enatioselective one-pot desymmetrization of meso-1,2,3-triol derivatives of myo-inositol by asymmetric acylation followed by successive kinetic resolution by CuCl_2-chirat diamine complex catalyzed asymmetric benzoylation. Enantioselective desymmetrization of meso-myo-inositol derivative was successfully applied to the asymmetric total synthesis of the key intermediate of phosphatidylinositol 3,5-bisphosphate
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Research Products
(2 results)
