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Development of a general and modular approach to C-nucleosides
Kubelka, Tomáš ; Štefko, Martin ; Bárta, Jan ; Joubert, Nicolas ; Urban, Milan ; Chapuis, Hubert Jean ; Hocek, Michal
Highly efficient and modular approach was developed for the synthesis of various types of new (het)aryl C-nucleosides. This protocol consists of the synthesis of haloaryl-C-nucleoside intermediates, followed by a functional group transformation to introduce various substituents. Using this approach protected 2′-deoxy-C-nucleosides bearing halogenated benzene, pyridine, thiophene, furane and pyrimidine were prepared. These intermediates were then submitted to a wide range of palladium-catalyzed reactions. The same approach was also used for preparation of C-nucleosides bearing ribofuranose moiety. Functional ribofuranosides bearing diverse substituted pyridine and benzene nucleobases were prepared in this way.
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Cyclic and acyclic phosphonate tyrosine ester prodrugs of acyclic nucleoside phosphonates
Williams, M. ; Krylov, I. S. ; Zakharova, V. M. ; Serpi, M. ; Peterson, L. W. ; Krečmerová, Marcela ; Kashemirov, B. A. ; McKenna, Ch. E.
A series of P-O ester derivatives of HPMPA, HPMPC, PMEA a (R)-PMPDAP was synthesized as potential anti-malarial prodrugs.
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Synthesis and structual assignment of novel 5´-epimeric 3´deoxy-3´,4´-didehydronucleoside-5´-C-phosphonates
Petrová, Magdalena ; Buděšínský, Miloš ; Klepetářová, Blanka ; Rosenberg, Ivan
Epimeric 5´-(RS) dialkyl 3-deoxy-3´,4´-didehydro-5´-C-phophonates were prepared by nucleophilic addition of various dialkyl phosphites to 3´-deoxy-3´,4´-didehydronucleoside-5´-aldehydes. Successful separation,crytstallisation and X-ray analysis of a pair of epimeric 5´-C-phosphonates, followed by correlation with a series of NMR parameters, led to efficacious configuration assignment of individual epimers in the mixtures.
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Acyclic Nucleoside Phosphonates as Inhibitors of Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase: New Anti-Malarial Chemotherapy Leads
Hocková, Dana ; Holý, Antonín ; Česnek, Michal ; Baszczyňski, Ondřej ; Tichý, Tomáš ; Krečmerová, Marcela ; Janeba, Zlatko ; Skinner-Adams, T. S. ; Naesens, L. ; Keough, D. T. ; de Jersey, J. ; Guddat, L. W.
Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRTase) is a widely recognized target for the discovery of new anti-malarial drugs. Specific acyclic nucleoside phosphonates (ANPs) inhibit HGXPRTase and possess anti-plasmodial activity. Within the framework of a SAR-study, the classical ANPs (e.g. PME-, PMP- and HPMP-derivatives) as well as novel series of compounds were tested to investigate their efficiency and selectivity on the inhibition of P. falciparum, P. vivax and human enzyme.
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