2002 Fiscal Year Final Research Report Summary
Synthetic Studies on Substituted Citrate Natural Products based on the Cinchona Alkaloid-Catalyzed Asymmetric Baylis-Hillman reaction
| Project/Area Number |
13672221
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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 | Tohoku University (2002)
Nagasaki University (2001) |
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Principal Investigator |
IWABUCHI Yoshiharu Tohoku University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (20211766)
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| Co-Investigator(Kenkyū-buntansha) |
HATAKEYAMA Susumi Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (20143000)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Baylis-Hillman reaction / asymmetric synthesis / asymmetric catalvsis / substituted citrate / tertiary amines / nucleophilic catalysis / cinchona alkaloids |
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| Research Abstract |
We have previously developed a highly enantioselective asymmetric BaylisHillman reaction which allows us to construct a wide variety of (α-methylene-β-hydroxy)esters with highly optical purity (>90% ee). The reaction relies upon the combinatorial use of two important reagents, 1,1,1,3,3,3-hexafluoroisopropyl acrylate as an activated alkene and (3R, 8K,,9S)-10,11-dihydro-3,9-epoxy-6'-hydroxy-cinchonane as a chiral, nucleophilic amine catalyst. In this research program, we have established the synthetic utility of the reaction system in a practical sense, by demonstrating its applicability to the crucial step in total syntheses of biologically active natural products, including a potent immunosuppressant amino acid, (-)-mycestericin E, and a novel proteasome inhibitor epopromycin B. The reaction was found to be applicable to α-keto ester-type substrates to furnish the corresponding α-methylene-β-alkoxycatbonyl-β-hydroxy)esters in good chemical yield with modest enantioselectivity. These reaction products should serve as useful synthons for the preparation of a series of substituted citratetype compounds.
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Research Products
(6 results)
