2001 Fiscal Year Final Research Report Summary
Development and Application of the Asymmetric Synthesis Using Chiral Oxonium Ion Species from Acetals
| Project/Area Number |
12672054
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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 | Osaka University |
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Principal Investigator |
FUJIOKA Hiromichi Osaka University, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (10173410)
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| Project Period (FY) |
2000 – 2001
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| Keywords | (R, R)-hydrobenzoin / cvclohexa-2. 5-dienyl methyl aldehyde / ene acetal / intramolecular bromoetherification / stenine / 3-endo-phenylnorbornene aldehyde / meso-1. 4-diols / asymmetric desymmetrization |
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| Research Abstract |
Development and application of the asymmetric synthesis using chiral oxonium Ions formed by an intramolecular haloetherification of ene acetals have been studied in two directions, 1 and 2.
1) Stereoselective construction of multi-chiral centers Synthetic study of stemona alkaloids : An intramolecular bromoetherification of the ene acetal, prepared fromeyelohexa-2, 5-dienyl methyl aldehyde diethyl acetal and (R,R)-hydrobenzoin, by NBS in the presence of MeOH proceeded stereoselectively to give the cyclohexene acetal by discrimination of the two olefins. Further transformations proceeded stereoselectively for the sake of conformational fixation by the acetal to form the three new asymmetric centers leading to the compound having the same configuration as stenine carbon skeleton. Thus obtained compound was converted to 9a-epi-stenine.
2) Asymmetric desymmetrization of meso-diols : Optically pure 2-exo-methyl-3-endo-phenyl-5norbornene-2-carboxaldehyde was obtained by our kinetically controlled optical resolution method. Using this auxiliary, deasymmetrization of meso-1, 4-diols was achieved in a highly enantioselective manner in a four step sequence : 1) acetalization of an aldehyde with a diol, 2) an intramolecular bromoetherification in the presence of MeOH followed by acid hydrolysis, 3) protection of the resulting alcohol, and 4) debromoetherification. The method was applied to meso-1,2- and 1,3-diols, and similar high enantioselectivity was observed.
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