Preparation of 2'-O-(β-Cyanoethyl phosphoramidites) of 3'-Deoxycytidine and 3'-Deoxyguanosine and Their Use for Solid-Phase Synthesis of Oligodeoxynucleotides Containing 2',5'-Phosphodiester Linkages

Article abstract of DOI:10.1021/jo00103a014

Convenient, preparative scale synthetic routes to 2'-O-(β-cyanoethyl N,N-diisopropylphosphoramidites) of 3'-deoxycytidine (1) and 3'-deoxyguanosine (2) are described.The 3'-deoxycytidine nucleoside 5 was constructed by a modified Hilbert-Johnson reaction in which N-(4-isobutyryl)cytosine (4) was ribosylated with anomeric acetate 3.Nucleoside 5 was converted to 5'-O-(dimethoxytrityl)-4-N-isobutyryl-3'-deoxycytidine (7) and phosphitylated to provide phosphoramidite 1.Access to derivatives of 3'-deoxyguanosine was provided by selective removal of the 3'-hydroxyl of guanosine (10).Thus, the 3'-O-thiocarbamate of 5'-O-(dimethoxytrityl)-2-N-(dimethylformamidyl)-2'-O-(triisopropylsilyl)guanosine (12) was reduced with tributyltin hydride and converted to phosphoramidite 2.In results to be reported elsewhere, phosphoramidites 1 and 2 were used to prepare oligodeoxynucleotides containing novel 2',5'-phosphodiester linkages using automated solid-phase DNA synthesis methods with average stepwise coupling yields of >97percent.