This PhD thesis reports the development of novel C-H activation strategies and aqueous-phase Suzuki-Miyaura cross-coupling reactions for the synthesis of modified deazapurine nucleobases. The methodologies of chemo- and regioselective synthesis of highly functionalized deazapurines have been developed by using modern C-H activation chemistry. Various functional groups such as amino-, imido-, silyl- and phosphonyl- were introduced by C-H activation reactions. Amino deazapurine derivatives were synthesized by developed Pd/Cu-catalyzed direct C-H amination and C-H chloroamination of 6-substituted 7-deazapurines with N-chloro-N- alkyl-arylsulfonamides. C-H imidation reactions of pyrrolopirimidines were performed under ferrocene catalysis with N-succinimido- or N-phtalimidoperesters. In order to obtain silylated derivatives, Ir-catalyzed C-H silylations of phenyldeazapurines with alkyl silanes were designed. Highly interesting deazapurine phosphonates were prepared by using Mn-promoted C-H phosphonation method and were further transformed into the corresponding phosphonic acids. All of the developed direct C-H functionalization reactions proceeded regioselectively at position 8 in deazapurine core, except for C-H silylation where reaction undergoes mainly as directed ortho C-H silylation on phenyl ring,...

A general and modular synthetic approach to 4-substituted phenyl, 2-substituted pyridin- 5-yl and 5-substituted pyridin-2-yl 2′-C-methyl-C-ribonucleosides as potential anti-HCV agents was developed. Addition of halo(het)aryllithium reagents to benzylated 2-C-methyl-D- ribonolactone gave the corresponding hemiketals, which were subsequently converted to the β-anomeric benzyl-protected bromo(het)aryl-C-nucleosides via either direct reduction (in the case of phenyl derivative) or acetylation followed by reduction of the resulting hemiketal acetates (in the case of pyridyl derivatives). The key halogenated (het)aryl-C-nucleoside intermediates were further transformed by Pd-catalyzed cross-coupling, hydroxylation and amination reactions affording series of protected C-nucleosides with small hydrophilic and hydrophobic substituents. The final protecting group removal was rather problematic, and different debenzylation methods, such as hydrogenation on Pd/C or treatment with BCl3, had to be optimized for each derivative to minimize the formation of side-products. The final C- nucleosides were also converted into their 5′-O-triphosphates, and biological activity screenings revealed that none of the free C-nucleosides possesses any antiviral activity in the HCV replicon assay, and none of their NTPs...