Nucleic Acids Research, 1992, Vol. 20, No. 8 1879-1882
© 1992
CHEMISTRY |
Selective O-phosphitilation with nucleoside phosphoramidite reagents
Department of Chemistry, Northwestern University Evanston, IL 60208, USA
*To whom correspondence should be addressed
On leave from the M.M.Shemyakin Institute of Bioorganic Chemistry, Moscow, Russia
Received February 5, 1992. Revised March 24, 1992. Accepted March 24, 1992.
In contrast to tetrazole, pyridlne hydrochloride/ imidazole converts nucleoside phosphoramidites to intermediates that show a high preference for phosphltllating hydroxyl groups relative to nucleoside amino groups. Use of this activating agent and incorporation of a pyrldine 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 methylphosphono-amldites and ribonucleoside phosphoramidites, as well as deoxyribonucleoside phosphoramidites, when high O/N selectively is not needed.