Synthesis of novel C‐2 substituted pyrimidine nucleoside analogs

A series of 2‐(2‐oxoalkylidene)‐4(1H)‐pyrimidinone nucleoside analogs were synthesized by the addition of the lithium enolates of methylketones to 2,5′‐ and 2,2′‐anhydrouridines and to 2,5′‐anhydrothymidines. Alternatively, 2‐thiouridine was alkylated with bromomethyl ketones to yield 2‐(2‐oxoalkyl)thio‐4(1H)‐pyrimidinone ribofuranosides in good yields. These intermediates were subsequently transformed into the title compounds via an Eschenmoser sulfur extrusion reaction. The 2‐(2‐oxoalkylidene)‐4‐(1H)‐pyrimidinone nucleoside analogs exhibit enol proton signals in their 1H nmr spectra indicative of hydrogen bonding between N‐3 and keto oxygen. These structures offer functional groups with potential for Watson‐Crick hydrogen bonding.