Studies on the Synthesis of Furo[3,2-d]pyrimidine C-Nucleosides: New Inosine Analogues with Antiprotozoan Activity

Methods are described for the synthesis of the α and β anomers of 7-D−ribofuranosylfuro[3,2-d]pyrimidines substituted at C-4 with either amino, oxo, thiono, or methylthio groups. The analogous 2,4-dithiono compounds are also described. The key steps involve the LDA-promoted cyclizations of the cyano ethers 3 and 14 to give, respectively, the substituted furan C-nucleosides A and 16. After separation of anomers, these compounds were subjected to a number of pyrimidine-ring-forming reactions to give the desired bicyclic C-nucleosides. The adenosine analogue 13 is markedly cytotoxic to mouse L1210 cells in vitro, and the inosine analogue 20 shows activity against the pathogenic protozoans Leishmania donovani and Trypanosoma gambiense.