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Unique Participation of Unprotected Internucleotidic Phosphodiester Residues on Unexpected Cleavage Reaction of the SiO Bond of the Diisopropylsilandiyl Group Used as a Linker for the Solid‐Phase Synthesis of 5′‐Terminal Guanylated Oligodeoxynucleotides
Author(s) -
Ushioda Masatoshi,
Kadokura Michinori,
Moriguchi Tomohisa,
Kobori Akio,
Aoyagi Morihiro,
Seio Kohji,
Sekine Mitsuo
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200209)85:9<2930::aid-hlca2930>3.0.co;2-2
Subject(s) - chemistry , guanosine , nucleophile , pyridine , nitro , linker , oligonucleotide , branching (polymer chemistry) , medicinal chemistry , bond cleavage , stereochemistry , phosphate , organic chemistry , catalysis , dna , biochemistry , alkyl , computer science , operating system
In connection with the synthesis of guanosine‐capped oligodeoxynucleotides on polymer supports, we found an unprecedented SiO 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)‐1 H ‐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 DMTrTpTOSi(iPr 2 )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.