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Chemical Synthesis And Modification Of Acyclic Nucleosides

Posted on:2014-09-26Degree:MasterType:Thesis
Country:ChinaCandidate:S WuFull Text:PDF
GTID:2251330401967364Subject:Organic Chemistry
Abstract/Summary:PDF Full Text Request
Human infectious diseases caused by viruses, increase with time because viruses reside in living bodycells during reproduction and propagation. Viruses are difficult to wipe out and tend to mutate, attacking thebody repeatedly and spreading diseases. Just like natural nucleosides, nucleoside compounds are made upof bases and ribose moieties. They have varying degrees of structural resemblance to natural nucleosides.Therefore, they can interfere with or directly attack the biosynthesis of proteins and nucleic acids.However,researchers involved in the development of nucleoside drugs have found that these drugs havethe disadvantages of strong toxic side effects with prolonged use and drug tolerance. Acyclic nucleosides,an important group of nucleoside drugs with low in mammalian toxicity and low in drug tolerance, excitechemists’ interest. Although modifications can be obtained in different ways, the present culturaldocumentary falls short of a systematic and practical summary. Therefore, our goal is to describe the mainsynthetical methods and detailed experimental procedures for most representative clinical drugs and theiranalogues.Tricyclic purine nucleoside derivatives, which are ring formation directly on the purine, usually havegood fluorescence and biological activities. They play a huge role in the diagnosis of pathogenesis of thegenetic diseases. However, the synthesis processes have some fault, such as, multi steps and low yields.Firstly, we studied the reactions of6-chloropurine with a variety of amino-acid esters. Then the C6positionof purine amino acid esters covented into the amino alcohols via a quick reduction in the presence ofsodium borohydride. Finally, the tricyclic or polycyclic purine nucleoside derivatives were obtained by theclosure of the amino alcohols purine nucleosides with purine N1atom in the presence of dichloro sulfoxide.We developed a novel method for the synthesis of tricyclic purine nucleoside analogues.The chemical transformations of pyridines are of great significance in organic synthesis since aromaticheterocycles have extremely potent chemical, biological, and pharmaceutical utilities. Additionally,2-(2,2-diarylvinyl)pyridine derivatives have been found higher relative binding affinity for the estrogen receptorfor the treatment of diseases. Although these compounds have good application prospects, they are stillrestricted by some problems, such as multi steps and high production cost. Herein, we developed a novelPd-catalyzed tandom reaction of2-methyl azaarenes, aromatic aldehydes and aryl iodides to form2-(2, 2-diarylvinyl) pyridine derivatives via C(sp3)-H bond activation and Heck reaction.The desired compounds’ structures were confirmed by HRMS,1H-NMR,13C-NMR.
Keywords/Search Tags:acyclic nucleoside, tricyclic purine nucleoside, tandom reaction, pyridine derivatives
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