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Synthesis of Benzene and Pyridine 2′‐ C ‐Methyl‐ C ‐ribonucleosides and ‐nucleotides
Author(s) -
Tokarenko Anna,
Poštová Slavětínská Lenka,
Klepetářová Blanka,
Hocek Michal
Publication year - 2015
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201501219
Subject(s) - chemistry , pyridine , nucleoside , benzene , catalysis , acetylation , reagent , nucleotide , stereochemistry , medicinal chemistry , combinatorial chemistry , organic chemistry , biochemistry , gene
Abstract 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 BCl 3 , 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.