Biomimetic synthesis and mechanistic studies of natural product polysulfanes.
Item
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Title
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Biomimetic synthesis and mechanistic studies of natural product polysulfanes.
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Identifier
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AAI3204953
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identifier
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3204953
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Creator
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Brzostowska, Edyta Monika.
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Contributor
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Adviser: Alexander Greer
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Date
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2006
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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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This thesis outlines an experimental and theoretical organic chemistry approach to address the structure and synthesis of polysulfane antitumor compounds and the origin of their biological activity.;The mechanism of decomposition of 1,2,3,4,5-benzopentathiepin and related polysulfanes represented by pentathiepins was studied. Theoretical and experimental studies were undertaken and revealed a possible decomposition of pentathiepin yielding thiozone (triatomic sulfur, S3). Expulsion of S3 is the result of intramolecular attack of the amine on the first sulfur atom of the pentathiepin ring. The decomposition of pentathiepin by expulsion of S3 is energetically preferred over decomposition by expulsion of S2. Theoretical studies were supported by experiments. Trapping experiments revealed higher susceptibility of penathiepins toward of S 3 transfer rather to S2. The study may contribute to understanding the mechanism of biological activity of naturally occurring pentathiepins.;An odd-even effect in stability of polysulfanes was uncovered by theoretical methods, which helped to predict the product distribution of an o -benzyne---elemental sulfur reaction. DFT calculations revealed an enhanced stability of odd versus even cyclic polysulfanes likely the result of adjacent sulfur atoms lone pair electrons adopting a staggered orientation. The discovery may explain the preference for formation of odd vs even polysulfanes found in Nature. We conducted study on an elemental sulfur addition to benzyne, which revealed the formation of pentathiepin, thithiole, thianthrene and tetrathiocin, which has not been observed before.;A biomimetic synthesis of biologically active polysulfanes via o-benzoquinone intermediates was also accomplished. The study was inspired by the fact that the biologically active polysulfanes isolated from ascidians may be involved in defense mechanism of tunicates where polysulfane synthesis my take place from available ingredients, elemental sulfur and dopamine. The laboratory modeled biosynthesis of polysulfanes involving catechol and sulfur in its reduced form allowed us to observe several polysulfane products with the structures reminiscent to the natural products.;Finally, the synthesis of several new substituted 1,2-dithiolan-3-one 1-oxides was accomplished.
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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.
