Cyclohexenyl Nucleosides and Related Compounds

Cis and trans-1-(4-hydroxy-2-cyclohexenyl)- and 1-(2-hydroxy-5-cyclohexenyl) thymines were obtained by stereospecific routes. Oxidation of the 1, 4-products afforded 1-(4-oxo-2-cyclohexenyl)thymine, the carbocyclic analog of a reportedly antiviral ketopyranosyl nucleoside. Exclusive 1, 6-conjugate addition occurred with heterocyclic bases and methyl 1, 3-cyclohexadiene-1-carboxylate. Reduction of the thymine adduct gave 1-(4-hydroxymethyl1-3-cyclohexenyl)thymine. Michael-type addition provided a direct route to 3-oxocycloalkyl nucleosides, and lactone nucleosides resulted from addition of bases to α-methylene-γ-butyrolactone. Anti-HIV screening revealed no activity for the new compounds.