A chiral synthesis of the DEF-rings of nogalamycin.
Item
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Title
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A chiral synthesis of the DEF-rings of nogalamycin.
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Identifier
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AAI9108195
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identifier
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9108195
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Creator
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Yin, Htwe.
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Contributor
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Adviser: Richard W. Franck
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Date
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1990
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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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Nogalamycin is a member of the anthracycline antibiotic family and is notable in possessing reduced cardiotoxicity compared to daunomycin and related compounds. The left hand portion of nogalamycin (DEF-rings) is different from the usual anthracyclines. An approach to the synthesis of DEF-rings of nogalamycin has been studied. The synthesis involves two key cycloadditions: (1) The regioselective cycloaddition of (2S)-2,3-O-cyclohexylidene-D-glyceronitrile oxide with furan to yield the furoisoxazolin 110, and (2) the regio- and stereoselective Bradsher cycloaddition of furoisoxazoline with 2-(2,4-dinitrophenyl) isoquinolinium chloride, followed by acid hydrolysis and base aromatization to yield the naphthaldehyde 118. A new method of Bradsher cycloaddition reaction, cycloaddition under pressure using soluble base has been described.;Naphthaldehyde 118 is oxidized to naphthol 121 before transforming the functional groups at the side chain. The LAH reduction of isoxazoline 123 to amino alcohol is face selective. The F-ring is achieved by Swern oxidation of alcohol 188. The naphthol 214 is oxidized to quinone 224, but the final reduction of quinone 224 to hydroquinone followed by acid cyclization to construct E-ring was not successful.
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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.
