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.
