IMPROVED STRATEGIES FOR POSTOLIGOMERIZATION SYNTHESIS OF OLIGODEOXYNUCLEOTIDES BEARING STRUCTURALLY DEFINED ADDUCTS AT THE N-2 POSITION OF DEOXYGUANOSINE
Bl. Decorte et al., IMPROVED STRATEGIES FOR POSTOLIGOMERIZATION SYNTHESIS OF OLIGODEOXYNUCLEOTIDES BEARING STRUCTURALLY DEFINED ADDUCTS AT THE N-2 POSITION OF DEOXYGUANOSINE, Chemical research in toxicology, 9(3), 1996, pp. 630-637
Improved methodology has been developed for preparation of oligodeoxyn
ucleotides bearing adducts on the N-2 position of guanine in which the
adduction reaction is carried out in homogeneous solution rather than
while the oligonucleotide is immobilized on a solid matrix. The metho
dology utilizes a new synthon, 2-fluoro-O-6-(trimethylsilylethyl)-2'-d
eoxyinosine (3) Nucleoside 3 is stable to the conditions of oligonucle
otide synthesis, but the O-6 protection is eliminated under very mild
conditions following displacement of the 2-fluoro group by amine nucle
ophiles. Oligonucleotides containing 3 could be removed from the solid
support by treatment with 0.1 M NaOH (8 h, rt) without disruption of
3. Reaction of the crude, partially deprotected oligonucleotide with (
R)-2-amino-2-phenylethanol in homogeneous solution, followed by remova
l of the remaining protective groups with NH4OH (60 degrees C, 8 h) an
d then 0.1% acetic acid, gave the adducted oligonucleotide in good pur
ity and yield. Alternatively, fully deprotected oligonucleotide contai
ning 3 could be prepared by use of labile phenoxyacetyl-type protectin
g groups on the exocyclic amino groups.