Chemical synthesis of oligonucleotides by use of phenylthio group

This review deals with recent studies of oligonucleotide synthesis using th e phenylthio group as the phosphate protecting group. Several fundamental p roperties of the P-S bond in phosphorothioate compounds are described in de tail. The chemical synthesis and properties of nucleoside phosphorothioate derivatives, which can be prepared via silyl phosphite intermediates, are d escribed. Several interesting and unique properties of a new useful phospho rylating reagent, S,S-diphenyl phosphorodithioate (PSS) are described with some examples involving an application to oligodeoxyribonucleotide synthesi s using the phenylthio group as the 5'-terminal or internucleotidic phospha te protecting group. The potential utility of pyridinium phosphonate (PPN) has been demonstrated as an efficient catalyst for dephenylthiolation of bi s(phenylthio)phosphorylated nucleoside derivatives, which is required for s tepwise condensation in these oligonucleotide syntheses via the phosphotrie ster approach. Further application of this thiophosphotriester method to th e solid-phase synthesis of oligodeoxyribonucleotides is described. The back ground of developments of bifunctional condensing reagents such as MDS and DDS and their application to the liquid phase synthesis of oligonucleotides are also reviewed. Several methods using oximate reagents and (Bu3Sn)(2)O are exemplified for removal of the phenylthio group from fully protected ol igonucleotides. The application of the phenylthio group as an activatable p rotecting group to the chemical synthesis of 7-methylguanosine (MMG)- and t rimethylguanosine (TMG)-capped oligonucleotides. Other applications of this activation strategy to the synthesis of naturally occurring nucleic acids are also described. Finally, a plausible mechanism of the present thiophosp hotriester method is discussed.