Chemoselective Acylation of Nucleosides

Abstract

Acylated nucleoside analogues play an important role in medicinal chemistry and are extremely useful precursors to various other nucleoside analogues. However, chemoselective acylation of nucleosides usually requires several protection and deprotection steps due to the competing nucleophilicity of hydroxy and amino groups. In contrast, direct protecting‐group‐free chemoselective acylation of nucleosides is a preferred strategy due to lower cost and fewer overall synthetic steps. Herein, a simple and efficient chemoselective acylation of nucleosides and nucleotides under mild reaction conditions, giving either O‐ or N‐acylated products respectively with excellent chemoselectivity is reported.

Diversification of Nucleoside Analogues as Potent Antiviral Drug Leads

“…Firstly, the methyl ester of the triazole nucleobase was transformed into the amide 20,[48][49][50]56 , and then the nucleoside analogues 10-12 were achieved by deprotection. In detail, from Diels-Alder adduct 7, the ribavirin analogue 10a and the isomer 10b were obtained by treatment with methanolic ammonia and subsequent acidic treatment for deprotection; while an additional esterification step 57,58 yielded the C5′-OH esters 10c,d. In the case of 8 and 9, the amidation conditions did not lead to cleavage of the iso-butyric acid esters (at pseudo-C6′), and analogues 93% [c] 72% [d] 10b 11b 12b…”

Design and Synthesis of Bicyclo[4.3.0]nonene Nucleoside Analogues

“…In detail, ribavirin analogue 10a and isomer 10b were obtained by treatment of 7 with methanolic ammonia and subsequent acidic treatment (TFA in H 2 O/MeOH). An additional esterification step 18 yielded C5′-OH esters 10c and 10d . In the case of 8 and 9 , amidation did not lead to cleavage of the iso -butyric acid esters (at pseudo-C6′), and analogues 11c , 11d , 12c , and 12d were isolated after acidic deprotection.…”