Synthesis, structural characterization and biological evaluation of 4'-C-methyl- and phenyl-dioxolane pyrimidine and purine nucleosides

摘要

Nucleoside analogues play an important role in antiviral, antibacterial and antineoplastic chemotherapy. Herein we report the synthesis, structural characterization and biological activity of some 4'-C-methyl- and -phenyl dioxolane-based nucleosides. In particular, alpha and beta anomers of all natural nucleosides were obtained and characterized by NMR, HR-MS and X-ray crystallography. The compounds were tested for antimicrobial activity against some representative human pathogenic fungi, bacteria and viruses. Antitumor activity was evaluated in a large variety of human cancer cell-lines. Although most of the compounds showed non-significant activity, 23 alpha weakly inhibited HIV-1 multiplication. Moreover, 22 alpha and 32 alpha demonstrated a residual antineoplastic activity, interestingly linked to the unnatural alpha configuration. These results may provide structural insights for the design of active antiviral and antitumor agents.