Synthesis and application of novel nucleoside phosphonates and phosphoramidites modified at the base moiety

Abstract

The H-phosphonates and phosphoramidites of 2'-deoxyisoguanosine, 2'-deoxyisoinosine, 5-aza-7-deaza-2'-deoxyguanosine, and N-1-methyl-2'-deoxyformycin A were prepared. The diphenylcarbamoyl group was chosen for the 2-O-protection of 2'-deoxyisoinosine and 2'-deoxyisoguanosine, and dimethylaminoalkylidene groups were used to block the amino function of the various monomers. The synthesis of isoguanine oligonucleotides was found to be much more efficient using the 2-O-protected building blocks compared to those without oxygen protection. Oligodeoxynucleotides containing 2'-deoxyisoguanosine and 2'-deoxycytidine form parallel duplex structures. The self-complementary duplex containing 5-aza-7-deaza-2'-deoxyguanosine and 2'-deoxycytidine forms a stable duplex in acidic solution (pH = 5.0) while it is destabilized under neutral conditions.