Approaches to the synthesis of idarubicin-C-glycoside.
Item
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Title
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Approaches to the synthesis of idarubicin-C-glycoside.
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Identifier
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AAI9924796
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identifier
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9924796
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Creator
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Belica, Peter Stefan.
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Contributor
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Adviser: Richard W. Franck
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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 | Chemistry, Pharmaceutical
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Abstract
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Idarubicin is an orally active anthracycline antitumor antibiotic that has entered clinical practice as a chemotherapeutic agent. Toxic side effects have been associated with the enzymatic cleavage of the idarubicin O-glycoside linkage and strategies for making an idarubicin-C-glycoside analog were explored. A new method for making C-glycosides was discovered employing a variant of the Ramberg-Backlund reaction. Easily prepared thioglycosides are oxidized to their sulfones, which were then subjected to standard Ramberg-Backlund conditions, i.e. a base plus halogenating agent. The products are exo glycals, which upon hydrogenation afford predominately the equatorial C-glycosides. The novel application was demonstrated with several sugars. The model approach to idarubicin-C-glycoside utilized daunosamine functionalized as the axial 1-hydroxymethyl compound 154 applying chemistry reported by Bednarski. The alcohol was converted, via the 1-iodomethyl C-glycoside 156, to benzylic thioether 159 and then by oxidation to sulfone 160. The sulfone was subjected to the Ramberg-Backlund conditions and hydrogenated to give an anomeric mixture of C-glycosides 162. The anomeric integrity of the axial C-glycoside was lost during the Ramberg-Backlund reaction.
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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.
