An efficient synthetic route to antiviral 2,3-dideoxy-2,3-didehydro-nucleosides,
such as 2,3-dideoxy and 2- or 3-deoxyribo-nucleoside
analogs, from available precursors is disclosed, with the option of introducing
functionality as needed. In one embodiment, a method for the preparation of -D
and -L-2,3-dideoxy-2,3-didehydro-nucleosides
is described that includes: activating a compound of structure (1)
##STR1##
wherein B is a pyrimidine or purine base and Y is O, S or CH2
with an acyl halide of the formula X-C(O)R1, X-C(O)C(R1)2OC(O)R1
or X-C(O)OR1 (wherein X is a halogen, and each R1
is independently hydrogen, lower alkyl, alkyl, aryl or phenyl); reducing
the resulting compound with a reducing agent to form a 2,3-dideoxy-2,3-didehydro-nucleoside;
and optionally deprotecting the nucleoside. The haloacylation of the first step
can form the 2-acyl-3-halonucleoside, the 3-acyl-2-halonucleoside,
or a mixture thereof.
