Synthesis of novel C-2 substituted pyrimidine nucleoside analogs

Article abstract of DOI:10.1002/jhet.5570300540

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.