Synthesis of Benzene and Pyridine 2-C-Methyl-C-ribonucleosides and -nucleotides

0454255 - ÚOCHB 2016 RIV DE eng J - Článek v odborném periodiku
Tokarenko, Anna - Poštová Slavětínská, Lenka - Klepetářová, Blanka - Hocek, Michal
Synthesis of Benzene and Pyridine 2-C-Methyl-C-ribonucleosides and -nucleotides.
European Journal of Organic Chemistry. Roč. 2015, č. 36 (2015), s. 7962-7983. ISSN 1434-193X. E-ISSN 1099-0690
Grant CEP: GA ČR GAP207/11/0344
Institucionální podpora: RVO:61388963
Klíčová slova: nucleosides * nucleotides * glycosides * antiviral agents * cross-coupling
Kód oboru RIV: CC - Organická chemie
Impakt faktor: 3.068, rok: 2015

A general and modular synthesis of substituted benzene and pyridine 2-C-methyl-C-ribonucleosides was developed. Benzyl-protected haloaryl-C-nucleoside intermediates were prepared by the addition of bromo(het)aryllithium reagents to a protected lactone, followed by acetylation and reduction. These halogenated intermediates were further transformed by Pd-catalysed cross-couplings, aminations, or hydroxylations. The final deprotection was rather troublesome, and different procedures involving catalytic hydrogenation on Pd/C, or treatment with BCl3, were optimized for each derivative. The final C-nucleosides were also all converted into the corresponding NTPs. None of the C-nucleosides showed any activity in the HCV replicon assay, and none of the NTPs showed any significant inhibition of the HCV polymerase.
Trvalý link: http://hdl.handle.net/11104/0254984