SYNTHESIS OF DEOXY, DIDEOXY AND DIDEHYDRODIDEOXY ANALOGS OF -(4-C-HYDROXYMETHYL-ALPHA-L-PENTOFURANOSYL)ADENINE

Condensation of i-O-benzoyl-4-C-benzoyloxymethyl-L-arabinofuranose wit h N6-benzoyladenine, catalyzed with tin tetrachloride, afforded nucleo side I, which upon partial deacetylation and subsequent mesylation was converted into O-methanesulfonyl-alpha-L-arabinofuranosyl)adenine (II I). 9-(2,5,6-Tri-O-acetyl-4-C-acetoxy methyl-3-0-methane lfonyl-alpha- L-arabinofuranosyl)-N6-benzoyladenine (V) was obtained by condensation of 1,2,5-tri-0 -4-C-acetoxymethyl-3-0-methanesulfonyI-L-arabinose wit h N6-benzoyladenine. Reaction of mesyl derivatives III and V with meth anolic sodium methoxide afforded 2',3'-anhydro nucleosides VIa and VII a, which were acetylated to give xymethyl-2,3-anhydro-alpha-L-ribofura nosyl)adenine (VIb) and xymethyl-2,3-anhydro-alpha-L-lyxofuranosyl)ade nine (VIIb). Epoxy derivative VIb was cleaved with bromotrimethylsilan e to l-2-bromo-2-deoxy-alpha-L-arabinofuranosyl)adenine (VIIIa); the s ame reaction with epoxy derivative VIIb afforded a mixture of 9-(5-0-a cetyl-4-C-acetoxy hyl-2-bromo-2-deoxy-alpha-L-xylo-furanosyl)adenine ( IXa) and l-3-bromo-3-deoxy-alpha-L-arabinofuranosyl)adenine (Xa). Thei r dehalogenation with tributylstannane and subsequent deacetylation le d to droXyMethyl-alpha-L-erythro-pentofuranosyl)adenine (VIIIc), ydrox y-methyl-alpha-L-threo-pentofuranosyl)adenine (IXc) and hydroxymethyl- alpha-L-threo-pentofuranosyl)adenine (Xc). l-2-bromo-2-deoxy-alpha-L-a rabinofuranosyl)adenine (VIIId), prepared by acetylation of VIIIa, on reductive elimination with Cu/Zn couple and subsequent deacetylation a fforded methyl-alpha-L-glycero-pent-2-enofuranosyl)adenine (XIb). roxy methyl-alpha-L-glycero-pentofuranosyl)-adenine (XIIb) was obtained eit her by catalytic hydrogenation of bromo derivative VIIId, followed by deacetylation, or by catalytic hydrogenation of didehydro derivative X Ib. The nucleosides synthesized were tested for antiviral activity.