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

Publication at Faculty of Science |
2015

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 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.