Selective O-phosphitilation with nucleoside phosphoramidite reagents.
In contrast to tetrazole, pyridine hydrochloride/imidazole converts nucleoside phosphoramidites to intermediates that show a high preference for phosphitilating hydroxyl groups relative to nucleoside amino groups. Use of this activating agent and incorporation of a pyridine hydrochloride/aniline wash step in the synthetic cycles permit synthesis of mixed base twenty-mer oligonucleotides from nucleoside reagents containing unprotected amino groups. This approach should be useful for the synthesis of oligonucleotide analogues containing substituents sensitive to reagents used in conventional deblocking steps. Pyridine hydrochloride itself is an effective reagent for activating nucleoside methylphosphonoamidites and ribonucleoside phosphoramidites, as well as deoxyribonucleoside phosphoramidites, when high O/N selectivety is not needed.
Gryaznov
S M
SM
Department of Chemistry, Northwestern University, Evanston, IL 60208.
Letsinger
R L
RL
D001483:Base Sequence; D015226:Dinucleoside Phosphates / Q000138:chemical synthesis*; D008969:Molecular Sequence Data; D009705:Nucleosides / Q000138:chemical synthesis*; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis*
D015226:Dinucleoside Phosphates; D009705:Nucleosides; D009838:Oligodeoxyribonucleotides; D009943:Organophosphorus Compounds