Palladium-catalyzed aryl aminations of halo nucleosides platinum-catalyzed synthesis of new benzo[c]phenanthrene derivatives and synthesis of a cis ring-opened amino triol from benzo[a]pyrene series 1 diol epoxide
Item
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Title
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Palladium-catalyzed aryl aminations of halo nucleosides platinum-catalyzed synthesis of new benzo[c]phenanthrene derivatives and synthesis of a cis ring-opened amino triol from benzo[a]pyrene series 1 diol epoxide
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Identifier
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d_2009_2013:f7064ded46be:11457
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identifier
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11902
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Creator
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Thomson, Paul F.,
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Contributor
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Mahesh K. Lakshman
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Date
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2012
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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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Organic chemistry | amination | benzo[a]pyrene | benzo[c]phenanthrene | halo nucleoside | palladium | platinum
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Abstract
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Palladium-catalyzed aryl amination has been utilized for synthesis of N6-aryl adenosines from silyl-protected 6-bromo and 6-chloropurine nucleosides and arylamines. Analysis of conditions revealed that for chloro analogues, 10 mol% palladium acetate/15 mol% Xantphos/Cs 2CO3 in toluene, at 100 ºC, was effective. For the bromo analogues 5 mol% Pd(OAc)2/7.5 mol% Xantphos was adequate. Generality of method was evaluated using a variety of arylamines. Synthesis of biologically relevant deoxyadenosine and adenosine dimers was then accomplished. This work compares the reactivities of 6-bromo and 6-chloropurine nucleosides in Pd-catalyzed aryl-amination reactions.;Synthesis of novel 5-methylbenzo[c]phenanthrene, 4,5-dihydrobenzo[ l]acephenanthrylene, and benzo[l]acephenanthrylene, as well as their putative dihydrodiol and diol epoxide metabolites, has been accomplished. These compounds are needed to understand the influence of substituents remote from the fjord region on molecular distortion, and to assess the metabolism and DNA damage as a function of molecular non-planarity. A new metal-catalyzed chemistry was utilized, and which complements known photochemical cyclization as a means to access such compounds. Briefly, Pd-catalyzed C-C bond formation of bromo benzaldehydes with naphthylboronic acids gave biaryl aldehydes. Corey-Fuchs olefination led to biaryl alkynes, which underwent platinum-catalyzed cyclizations to yield the requisite parent hydrocarbons and precursors to the putative metabolites. The metabolites display a diequatorial arrangement of the hydroxyls and X-ray crystallographic data showed decreases in the overall molecular distortion upon remote functionalization. Biological evaluation is anticipated to understand the effect of molecular distortion and subsequent cellular events.;Diastereoselective synthesis of (+/-)-10beta-amino-7beta,8alpha,9beta-trihydroxy-1,2,3-4-tetrahydrobenzo[ a]pyrene was accomplished from (+/-)-7beta,8alpha-dibenzoyloxy-1,2,3-4-tetrahydrobenzo[ a]pyrene. This is required to synthesize nucleoside adducts produced by a cis ring-opening of benzo[a]pyrene diol epoxide 1. The dihydrodibenzoate was converted to the diol epoxide and then reacted with lithium chloride and acetic anhydride to give a peracyl trans chloro triol with a benzylic chloride. Displacement of chloride by azide, deprotection of acyl groups, and reduction of the azide afforded the requisite amino triol. This compound will be used to synthesize deoxyadenosine and deoxyguanosine adducts (the latter have not been synthesized to date).
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Chemistry
