Direct synthesis of 8-fluoro purine nucleosides via metalation-fluorination
Arun K Ghosh1, Pallavi Lagisetty, Barbara Zajc
1Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, New York 10031, USA.
Abstract:
A straightforward access to protected 8-fluoro nucleosides via metalation-electrophilic fluorination under heterogeneous reaction conditions is reported. This is the first synthesis of 8-fluoro-2'-deoxyribonucleoside derivatives. Phenylsulfonyl substituted nucleosides are accompanying byproducts, possibly indicating a competing radical process. Higher yields of 8-fluoro derivatives were obtained with 2'-deoxyribonucleosides, as compared to ribonucleosides. Deprotection of the hydroxyl groups leading to 8-fluoro-2'-deoxyadenosine using TASF in methylene chloride demonstrates the compatibility of desilylation with 8-fluoro substituted nucleosides. NMR data indicate a syn conformation of the 8-fluoro derivatives.
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