Direct synthesis of 8-fluoro purine nucleosides via metalation-fluorination.
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.
Ghosh
Arun K
AK
Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, New York 10031, USA.
Lagisetty
Pallavi
P
Zajc
Barbara
B
D003853:Deoxyribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D054879:Halogenation; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D009690:Nucleic Acid Conformation; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry; D017655:Silicon Compounds / Q000737:chemistry*; D013237:Stereoisomerism
D003853:Deoxyribonucleosides; D006845:Hydrocarbons, Fluorinated; D011687:Purines; D017655:Silicon Compounds