| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
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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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