497070-23-2Relevant academic research and scientific papers
Unique participation of unprotected internucleotidic phosphodiester residues on unexpected cleavage reaction of the Si-O bond of the diisopropylsilandiyl group used as a linker for the solid-phase synthesis of 5′-terminal guanylated oligodeoxynucleotides
Ushioda, Masatoshi,Kadokura, Michinori,Moriguchi, Tomohisa,Kobori, Akio,Aoyagi, Morihiro,Seio, Kohji,Sekine, Mitsuo
, p. 2930 - 2945 (2007/10/03)
In connection with the synthesis of guanosine-capped oligodeoxynucleotides on polymer supports, we found an unprecedented Si-O bond cleavage reaction, which occurred when polymer-linked oligodeoxynucleotides having unprotected internucleotidic phosphate groups were allowed to react with the guanosine 5′-phosphorimidazolide derivative 18 in the presence of 4-nitro-6-(trifluoromethyl)-1H-benzotriazol-1-ol (Ntbt-OH) as an effective activator in pyridine. This side reaction was confirmed by the fact that the liquid-phase reaction of DMTrTpT-O-Si(iPr2)OEt 42 with a simpler model compound, methyl phosphorimidazolide 34, in the presence of Ntbt-OH gave DMTrTpT 43. It turned out that the side reaction hardly occurs without unprotected internucleotidic phosphate groups on oligodeoxynucleotides. The detailed study of this side reaction disclosed that Ntbt-OH directly attacks the Si-atom to release oligonucleotides from the resin. It is likely that Ntbt-OH serves as a very strong nucleophile in pyridine, especially to the Si-atom of the linker.
