Modified nucleosides and methods of making and using the nucleosides are
disclosed. The compounds can be prepared by reacting nucleoside starting materials
that contain a suitable leaving group at one or more of the carbon atoms in the
purine or pyrimidine ring, with a vinylstannane, carbon monoxide, and a palladium
catalyst to provide 1-ene-3-one intermediates. These intermediates are then reacted
with suitably functionalized primary or secondary amines via a Michael reaction.
When the intermediate is a 5-position modified pyrimidine ring, and the amine contains
a second hydrogen, it can do a second Michael reaction with the ene-one or the
ene-imine in the pyrimidine ring. Appropriate modification of the amine reactant
can yield products with various bioactivities. The nucleosides can be used therapeutically
as anti-cancer, anti-bacterial or anti-viral drugs. The nucleosides can also be
used for diagnostic applications, for example, by incorporating a radiolabel or
fluorescent label into the molecule. The nucleosides can be used to prepare oligonucleotides
for use in various applications, either alone or in combination with other modified
nucleosides and/or naturally occurring nucleosides.
