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 H-1 nmr spectra indicative of hydrogen bonding between N-3 and keto oxygen. These structures offer functional groups with potential for Watson-Crick hydrogen bonding.