Donald A. Upson

Achiral internucleoside linkages: CH2-CH2-NH and nH-CH2-CH2 linkages

The synthesis of CH2-CH2-NH and NH-CH2-CH2 internucleoside linkages are described. Antisense oligonucleosides containing these dimer modifications hybridized to the sense sequence. Furthermore incorporation of these backbone modifications enhanced the nuclease resistance of the antisense strand.

3′-Substituted pyrimidines via alkylation-opening of 2,3′-cyclothymidine

Abstract Substituted thymidine derivatives are of interest because of their potential antiviral properties. We demonstrate a general strategy for synthesis of 3′-substituted thymidine derivatives, consisting of activation via N-3 alkylation of 2,3′-cyclothymidine followed by nucleophilic opening at the 3′-position. Examples include demonstration of carbon-carbon bond formation at the 3′-position.

Achiral internucleoside linkages 3: CH2NHCH2 linkage

Abstract A stereoselective method for the synthesis of 3′-α-or 3′-β-carbon substituted pyrimidine nucleosides was developed. The synthesis of the CH 2 NHCH 2 linkage is described. The linkage offers enhanced resistance to 3′-exonuclease.