Synthesis, Antiviral and Cytostatic Evaluation of Unsaturated Exomethylene and Keto D ‐Lyxopyranonucleoside Analogues

This report describes the synthesis of unsaturated exomethylene lyxopyranonucleoside analogues as potential biologically active agents. Commercially available 1,2,3,4‐tetra‐ O ‐acetyl‐α‐ D ‐lyxopyranose 1 was condensed with silylated thymine and uracil, respectively, deacetylated and acetalated to afford 1‐(2,3‐ O ‐isopropylidene‐α‐ D ‐lyxopyranosyl)thymine 4a and 1‐(2,3‐ O ‐isopropylidene‐α‐ D ‐lyxopyranosyl)uracil 4b . The new derivatives 1‐(2,3,4‐trideoxy‐4‐methylene‐α‐pent‐2‐enopyranosyl)thymine 8a and 1‐(2,3,4‐trideoxy‐4‐methylene‐α‐pent‐2‐enopyranosyl)uracil 8b were prepared via two different key intermediates, 7a , b and 13a , b in order to elucidate the influence of 2′,3′‐unsaturation and to clarify the difference between the keto and exomethylene group on the biological activity of the target molecules. Compounds 7a , b , 8a , b , and 13a , b were evaluated for their antiviral and cytostatic activity using several virus strains and cell lines. Whereas no marked antiviral activity was noticed, 13a and 13b showed a cytostatic activity that ranged between 7 and 23 μM for 13a and 26 and 38 μM for 13b against murine leukemia L1210, human lymphocyte Molt4/C8 and CEM cells, and human breast carcinoma MCF7 cells.