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.