Stereospecific synthesis nucleoside phosphorothioates

Stereospecific Synthesis and Assignment of Absolute Configuration at Phosphorus in Nucleoside 3 - and 5 -0-Arylphosphorothioates and Nucleoside Cyclic 3, 5 -Phosphorothioates... 

The early attempts to use relatively easily available diastereomerically pure nucleoside 3 -0-(2-cyanoethyl-AT,AT-diisopropylphosphoramidite) monomers for the stereospecific synthesis of PS-Oligos failed because of inevitable racemiza-tion of Pm intermediate caused by an excess of lff-tetrazole necessary for efficient elongation of oligonucleotide chain [13]. An idea to use for that purpose appropriately protected nucleosides functionalized at 3 -0 position with 2-thio-1,3,2-oxathiaphospholane moiety arose from the studies on the reactions of di-substituted phosphorothioates with oxiranes [14,15], and in particular from the observation that PS-PO exchange in 0,0-diphenyl phosphorothioate (8) upon treatment with ethylene oxide in methanol solution resulted in formation of... 

The discovery of antiviral activity of oligo(nucleoside methane-phosphonate)s (44) and oligo(nucleotide phosphorothioate)s (45-47), so far chemically prepared by the nonstereocontrolled methods, attracted the attention of several research establishments to the search for stereospecific synthesis of those classes of oligonucleotide analogs. Since their routine synthesis via phosphoramidite or any other approach leads to the mixture of m diastereoisomers, the question may be asked whether desired antiviral activity is owing to all m components of diastereo-isomeric mixture or to the fraction possessing the proper sense of chirality at each modified phosphate. Moreover, since the seminal works of... 

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