Synthesis of biologically active molecules: Novel antifungals and retinal analogs.
Item
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Title
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Synthesis of biologically active molecules: Novel antifungals and retinal analogs.
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Identifier
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AAI9909403
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identifier
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9909403
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Creator
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Peng, Langu.
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Contributor
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Adviser: Valeria Balogh-Nair
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Date
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1998
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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, Biochemistry | Chemistry, Pharmaceutical
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Abstract
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Part I. Syntheses of spacer-armed retinal analogs were undertaken to serve as tools to investigate the tertiary structures of retinal proteins, and to serve as models in the design of biopolymer based devices. A common key intermediate was prepared in a multi-step synthesis. Derivatizations of this intermediate afforded three analogs with functionalized spacer-arms attached to a seco-ring. The first analog contains an 11-carbon spacer-arm. In the second analog, the spacer is of twelve carbon length and contains a polar carboxyl terminus. In the third analog, designed to generate orderly arrays of bacteriorhodopsin on gold, a disulfide bond joins two spacer-armed retinyl moieties.;Part II. Syntheses of oxaziridines, metallomacrocycles and nitronyl nitroxides were undertaken to demonstrate the antifungal potential of these novel pharmacophores. Three bisoxaziridines, the first example of a trisoxaziridine, a macrobicyclic hexaoxaziridine, a Ni(II)-macrocyclic amide complex, and a dendrimer-based tris(nitronyl nitroxide) were synthesized efficiently. The antifungal activity of the compounds synthesized was evaluated in collaborative studies. These studies established that at least three oxaziridine units per molecule are necessary to achieve high levels of antifungal activity, and they demonstrated the usefulness of metallomacrocycles as antifungals. The tris(nitronylnitroxide) had antifungal activity against P. carinii equivalent to that of the current drug, thereby strongly supporting the oxidoredox pharmacophore hypothesis.
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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.
