Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(β-D-Hexofuranosyl)adenine

Condensation of 1,2-di- O -acetyl-3,5,6-tri- O -benzoyl-D-glucofuranose with N 6 -benzoyladenine, catalyzed with tin tetrachloride, afforded nucleoside I . Partial deacetylation of I , followed by mesylation, gave 9-(3,5,6-tri- O -benzoyl-2- O -methanesulfonyl-β-D-glucofuranosyl)adenine ( III ). 9-(2,5,6-Tri- O -acetyl-3- O -methanesulfonyl-β-D-glucofuranosyl)- N 6 -benzoyladenine ( IV ) was prepared by condensation of 1,2,5,6-tetra- O -acetyl-3- O -methanesulfonyl-D-glucofuranose with N 6 -benzoyladenine. Reaction of mesyl derivative III with methanolic sodium methoxide and of mesyl derivative IV with methanolic ammonia led to 2',3'-anhydronucleosides V and VI which were acetylated to give the respective 9-(5,6-di- O -acetyl-2,3-anhydro-β-D-mannofuranosyl)adenine ( VII ) and 9-(5,6-di- O -acetyl-2,3-anhydro-β-D-allofuranosyl)adenine ( VIII ). Epoxy derivative VII was cleaved with bromotrimethylsilane, affording a mixture of 9-(5,6-di- O -acetyl-2-bromo-2-deoxy-β-D-glucofuranosyl)adenine ( Xa ) and 9-(5,6-di- O -acetyl-3-bromo-3-deoxy-β-D-altrofuranosyl)adenine ( XIa ), epoxy derivative VIII was cleaved analogously to give 9-(5,6-di- O -acetyl-3-bromo-3-deoxy-β-D-glucofuranosyl)adenine ( XIIa ). Their dehalogenation with tributylstannane and subsequent deacetylation led to 9-(2-deoxy-β-D- arabino -hexofuranosyl)adenine ( Xc ), 9-(3-deoxy-β-D- arabino -hexofuranosyl)adenine ( XIc ) and 9-(3-deoxy-β-D- ribo -hexofuranosyl)adenine ( XIIc ). 9-(2,5,6-Tri- O -acetyl-3-bromo-3-deoxy-β-D-glucofuranosyl)adenine ( XIId ), which was prepared by acetylation of XIIa , on reductive elimination with Cu/Zn couple and subsequent deacetylation gave 9-(2,3-dideoxy-β-D- erythro -hex-2-enofuranosyl)adenine ( XIV ). 9-(2,3-Dideoxy-β-D- erythro -hexofuranosyl)adenine ( XVI ) was obtained either by catalytic hydrogenation of bromo derivative XIId followed by deacetylation, or by catalytic hydrogenation of didehydro derivative XIV . The synthesized nucleosides were tested for antiviral activity.