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Synthesis of novel types of C-nucleosides
Kubelka, Tomáš ; Hocek, Michal (advisor) ; Trnka, Tomáš (referee) ; Moravcová, Jitka (referee)
of PhD Thesis: Synthesis of novel types of C-nucleosides General and modular approach for the preparation of disubstituted pyrimidine and pyridine C-2'-deoxyribonucleosides and benzyl homo C-ribonucleosides was developed. The key intermediate 2,4-dichloropyrimidine C-2'-deoxyribonucleoside was efficiently prepared from easily available TBS-protected deoxyribose glycal in three steps. Its mild nucleophilic substitutions or cross-coupling reactions proceeded regioselectively at position 4, while at elevated temperatures or with excess of reagent, a double substitution occurred. The 2-chloro-4-substituted intermediates underwent another substitution or coupling to afford a two-dimensional library of diverse 2,4-disubstituted pyrimidin-5-yl C-2'-deoxyribonucleotides. Modular methodology for the synthesis of 2,6-disubstituted pyridine C-2'-deoxyribonucleosides was based on the Heck coupling of bromo-chloro-iodopyridines with TBS-protected deoxyribose glycal. Obtained 2-bromo-6-chloro- and 6-bromo-2-chloropyridin-3-yl deoxyribonucleosides were used for further transformations. Some of their Pd-catalyzed cross-coupling reactions proceeded chemoselectively at the position of the bromine, whereas nucleophilic substitutions were unselective and gave mixtures of products. The mono- substituted intermediates...
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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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