2004 Fiscal Year Final Research Report Summary
| Project/Area Number |
14370717
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Chiba University |
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Principal Investigator |
ISHIKAWA Tsutomu Chiba University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究院, 教授 (20114233)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Toshiko Chiba University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究院, 助教授 (40120323)
SEKI Hiroko Chiba University, Chemical Analytical Center, Associate Professor, 分析センター, 助教授 (60114245)
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| Project Period (FY) |
2002 – 2004
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| Keywords | guanidine / chiral catalyst / guanidinium ylide / aziridine / aldehyde / asymmetric synthesis / building block |
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| Research Abstract |
Guanidinium ylide-paiticipated asymmetric aziridination was precisely examined. Thus, the formation of the ylides was confirmed by NMR spectroscopy. Acid anhydrides, like silica gel, could contribute to the fragmentation of adduct intermediates from guanidinium ylides and aryl aldehydes to aziridine and urea products. Examination of reaction using a variety of p-substituted benzaldehydes allowed us to categorize the aziridination to two groups dependent upon the substituents, causing different reaction rate and stereochemistry of aziridine products. The enatio-and diastereoselectivities could be reasonably explained by Hammett analysis.
This aziridine synthesis is sensitive to the steric bulikiness of the stalling guanidinium salts and, thus, low reactivity was observed on substituted guanidinium salts. α,β-Unsaturated aldehydes, like aryl aldehydes, could serve as aldehyde substrates to afford aziridines with high enantioselectivity. Straight-forward aziridine formation was observed when tertiary guanidine are subjected to not only the reaction in the presence of alkylating agents but also the reaction with styrene oxides.
On the other hand in the course of exploiting the potential functionality of chiral guanidines guanidine-catalyzed asymmetric chromanone construction was examined by application of intramolecular Michael reaction expected asymmetric induction was observed. General preparation method for the polymer-supported guanidines as potential environment-directed catalysts was basically established. Atom-economical synthesis of biologically active N-containing compounds using chiral aziridines as building blocks was developed. Thus, ring-opening reactions of aziridine skeletons were examined either under reductive conditions or in the presence of nucleophiles. As a example enantioselective total synthesis of D-erythro-sphingosine was achieved. Furthermore, chemical modification of aziridines was attempted for their ring-expansion to β-lactam skeletons
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