title: Development of new methods for the synthesis of RNA oligonucleotides having base-labile functional groups.
abstract: In the previous study, we developed a method for O-selective phosphorylation, i.e., "the activated phosphite method" for DNA synthesis without base protection. However, the O-selectivity was low in RNA synthesis when the activated phosphite method was used. In this paper, we developed two new methods for synthesis of RNA oligomers having base-labile functional groups on polymer supports. One is the N-unprotected phosphoramidite method involving P(III)-N bond cleavage. The selectivity of the phosphorylation in RNA synthesis increased to more than 99% by posttreatment of the undesired P(III)-N bonds with 6-nitoro-HOBt and was independent of the kind of protecting groups at the 2' position. Another method is the RNA synthesis involving deprotection of protecting groups of the nucleobases under acidic conditions. It was found that an N,N-dialkylaminomethlene (DAF) group could be easily removed by heat-induced deprotection using HOBt as an acidic promoter.
authors.affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Midoriku, Yokohama, 226-8501, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohkubo
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Noma
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Kuwayama
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Tsunoda
authors.forename: Kohji
authors.initials: K
authors.lastname: Seio
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Sekine
mesh_terms: D001671:Biochemistry / Q000379:methods; D009843:Oligoribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D010766:Phosphorylation
chemical_list: D009843:Oligoribonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite