Palladium-phosphinous acid-catalyzed carbon-carbon and carbon-heteroatom bond formation and synthesis of new antimalarial drugs
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Thesis (Ph.D.)--Georgetown University, 2008.; Includes bibliographical references. Palladium-catalyzed carbon-carbon and carbon-heteroatom bond forming reactions have gained increased importance in organic transformations. Palladium-phosphinous acids and chlorophosphines have proved to be useful in cross-coupling reactions due to their high catalytic activity and to their stability to air and moisture. In this thesis, it is reported that palladium-phosphinous acids can catalyze the Suzuki coupling reactions of aryl and acyl chlorides to afford biaryls and ketones in high yields. Since palladium-phosphinous acids proved useful for oxidative esterification of aldehydes, a similar one-pot procedure generating amides was developed. Moreover, new alkylarylphosphinous acids exhibiting a naphthyl, a biphenyl or a 2,6-dimethylphenyl group were synthesized and applied to transition metal-catalyzed cross-coupling reactions. The spread of chloroquine (CQ) resistant malaria strains has led to the development of new heme-targeted antimalarials. It has been established that the pharmacophore of CQ consists of a terminal dialkylamino side chain as well as a 7-chloroquinolyl ring. The basic CQ side chain and the quinolyl N are known facilitate the accumulation of the drug in the digestive vacuole of the malaria parasite. In an attempt to find CQ analogues that are effective against both chloroquine resistant (CQR) and chloroquine sensitive (CQS) strains of the malaria parasite, a series of 4N and 4O chloroquine derivatives exhibiting different side chain structures and CQ amides were prepared and tested. Some of these compounds exhibit better antimalarial activity over CQ.
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http://hdl.handle.net/10822/552879Date Published
2008Subject
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Georgetown University
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TRANSITION METAL-CATALYZED CARBON-CARBON AND CARBON-NITROGEN BOND FORMATION AND ASYMMETRIC CATALYSIS WITH BISOXAZOLIDINE LIGANDS
(Georgetown University, 2012)Palladium-phosphinous acids and chlorophosphine analogues have attracted increasing interest due to their high catalytic activity in various organic transformations, long shelf-life and facile handling. In this thesis, it ...
