Synthesis of polyhydroxyindolizidines and analogues: A triple reductive amination approach.
Item
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Title
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Synthesis of polyhydroxyindolizidines and analogues: A triple reductive amination approach.
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Identifier
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AAI9946236
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identifier
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9946236
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Creator
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Zhao, Hang.
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Contributor
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Adviser: David R. Mootoo
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Date
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1999
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Organic
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Abstract
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The polyhydroxyindolizidines, castanospermine, and swainsonine exhibit potential activity against various glycosidases. They have shown promise in the treatment of cancer and AIDS and other health disorders. As result there has been considerable interest in the synthesis of analogues of those compounds.;Our approach to the polyhydroxyindolizidines relates the target to a tricarbonyl precursor via a triple reductive amination (TRA) reaction. A key step in the preparation of the tricarbonyl precursor was the haloetherification reaction of allylated C5 furanosides or C6 pyranosides. The haloetherification reaction was previously developed in this laboratory. The required allylated saccharide was obtained from the appropriate monosaccharide, through different allylation procedure.;The plan was first tested on castanospermine, and then extended to related polyhydroxyindolizidines, and to pyrrolizidine and quinolizidine analogues. The methodology successfully established the complex bicyclic framework with complete stereocontrol in a single step from the tricarbonyl precursor. The yield of the TRA reaction was somewhat modest for the indolizidines (40--50%), and very low for the quinolizidine (30%) and pyrrolizidine (20%).;The mechanism of the TRA was also investigated. The conclusions were based on comparison of the yields and stereochemical results for selected TRA and double reductive amination cyclizations. For the indolizidine systems the reaction could proceed through the initial formation of either a five or six membered ring iminium ion. However, it appears that formation of six membered iminium ion is the favored process. It is also possible that a bicyclic [4.3.0] iminium ion species could be involved. The lower yields obtained for the quinolizidine and pyrrolizidine systems might be an indication of a slower rate of formation of the associated iminium ions, which lead to increased formation of side products resulting from polyamination.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
