New synthetic approach to nucleoside phosphorofluoridates and fluoridites. Novel type of phosphitylating reagents containing 4-nitrophenoxy group.

New DNA analogues which have -OP(O)F-O internucleotide linkage are prepared by two methods. One route is based on transformation of a deoxynucleoside phosphoroimidazolidate by benzoylfluoride into the corresponding phosphorofluoridate. Alternative route begins with condensing of a new type of phosphoroamidites containing 4-nitrophenoxy group: N,N,N',-tetraisopropyl-O-4-nitrophenylphosphorodiamidite 9 to yield the dideoxynucleoside-4-nitrophenylphosphites which are readily converted into the corresponding dideoxynucleoside phosphorofluoridates and their sulfur analogues. Second part of this paper illustrates application of the N,N-diisopropyl-O-methyl-O-4-nitrophenylphosphoroamidite 12 and N,N-diisopropyl-O-4-nitrophenyl-P-methylphosphonoamidite 16 in efficient synthesis of dideoxynucleotides and their thio- and selenoanalogues.