Conformationally locked nucleoside analogs. Synthesis of 2 '-deoxy-2 '-C, 4 '-C-bridged bicyclic nucleosides

1-alpha-Methylarabinose was converted, in three steps, to 2-deoxy-2-methyle neribose derivative 3, which was subjected to hydroboration to give 2-alpha -hydroxymethyl derivative 4 exclusively; 4 was converted to 2,4-bis(hydroxy methyl)ribose derivative 6 in four steps. Mesylation, detritylation, and ri ng closure, followed by hydrolysis of the mesyl group at O5, gave 3,6-dioxa bicyclo[3,2,1]octane derivative 8. After acetylation, 8 was coupled with si lylated 6-chloropurine to give desired alpha- and beta-bicyclic-sugar nucle osides.