Synthesis of Nucleosides and Deoxynucleosides via Gold(I)-Catalyzed N-Glycosylation of Glycosyl (Z)-Ynenoates.

Abstract

Nucleoside analogues are widely used as anticancer and antiviral drugs. Here, we develop a highly efficient gold(I)-catalyzed N-glycosylation approach for versatile synthesis of various types of nucleosides and deoxynucleosides with glycosyl (Z)-ynenoates as donors. The wide scope of the N-glycosylation approach was demonstrated by the synthesis of 31 pyrimidine nucleosides and 8 purine nucleosides. Remarkably, the gold(I)-catalyzed N-glycosylation of pyranosyl (Z)-ynenoates with purines was found to be very effective for regioselective synthesis of pyranosyl N9 purine nucleosides. Based on the catalytic N-glycosylation approach, convenient synthesis of two 5'-deoxynucleosides drugs (capecitabine and galocitabine), four 2'-deoxynucleoside drugs (floxuridine, trifluridine, decitabine and cladribine), four 3',5'-dideoxynucleoside analogues, and four 2',5'-dideoxynucleoside analogues was achieved in a collective manner.