DIISOPROPYLSILYL BIS(TRIFLUOROMETHANESULFONATE)

Diisopropylsilyl bis(trifluoromethanesulfonate) has more recently been used to prepare diisopropylsilyl-linked oligonucleotide analogs. Silylation of 5'-O-(dimethoxytrityl)-2'-deoxynucleosides using diisopropylsilyl bis(trifluoromethanesulfonate) and the hindered base 2,6-di-t-butyl-4-methylpyridine (Dtbp) provided quantitative yield of 3'-O-diisopropylsilanols (eq 2). Hence, silylation of 5'-O-(dimethoxytrityl)thymidine, N6-benzoyl-2'-deoxy-5'-O- (dimethoxytrityl)adenosine, N4-benzoyl-2'-deoxy-5'-O-(dimethoxytrityl) cytidine, and N2-isobutyryl-2'-deoxy-5'-O-(dimethoxytrityl) guanosine gave the desired products 5a–d in excellent yields.
Coupling of products 5a–d with unprotected thymidine resulted in formation of 3',5'-linked dinucleosides 6a–d selectively, and the dimer 7 from reaction with secondary hydroxyl group of thymidine was not observed (eq 3). Subsequent silylation and coupling with another molecule of thymidine gave 3,5- linked trinucleoside 8 in 76% yield (eq 4). A tetrathymidylate oligomer was prepared by 3'-O-silylation of 8 followed by coupling with thymidine. Although no self-condensation was observed, only 30% of the product 9 was obtained after purification by preparative HPLC.