Nitro-Activated Nucleobase Exchange in the Synthesis of 2′-Fluoro-2′-Deoxyribonucleosides

Abstract

Functionalized nucleosides bearing pyrimidine or purine bases can be prepared by activation of accessible pyrimidine nucleosides and subsequent transglycosylation. Nitration of lumicitabine, a 2′-fluoro-2′-deoxycytidine class antiviral agent, and its 2′-fluoro-2′-deoxyuridine precursor produce the same 5-nitro-2′-fluoro-2′-deoxyuridine. Under Vorbrüggen conditions, 5-nitrouracil serves as the leaving nucleobase and enables exchange with pyrimidine and purine nucleobases to anomeric 2′-fluoro-2′-deoxyribonucleosides in favor of β-anomers generally. The strategy is also applied in the isotopic labeling of 2′-fluoro-2′-deoxyuridines.