Nucleoside phosphorothioates stereospecific

It is a well established property that many enzymes interact in a stereospecific manner with the different diastereoisomers of nucleoside phosphorothioates. For example, when AMP is substituted by adenosine S -t7-monopho phorothioate (AMPS), adenylate kinase-catalysed phosphorylation occurs specifically at the pro-R oxygen atom to give (5ip)-ADPaS. The stereospecificity results from the restricted orientation of the P-O and P-S bonds in the enzyme active site. While it is known that changing the metal ion can perturb the stereoselectivity, Tsai and... 

Fuji, M, Ozaki, K., Sekine, M., and Hata, T. (1987) Acylphosphonates 7 A new method for stereospecific and stereoselective generation of dideoxyribo-nucleoside phosphorothioates via the acylphosphonate Intermediate. Tetrahedron 43, 3395-3407... 

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... 

Much more promising seems to be another, so far hypothetical, assumption that an access to stereo-defined oligo (nucleoside phosphoro-thioates) will allow stereospecific conversion of phosphorothioate function to 0-alkyl functions, for example, by selective 5-alkylation and conversion of 5-alkyl phosphates into 0-alkyl phosphates (24). However, one has to take into account potential problems with selective 5-alkylation in the presence of other nucleophilic centers, mostly on the nucleic bases. 

Stereospecificities of the Formation of Dinucleoside (3 -5 ) Phosphorothioates (10) in Reaction Between Corresponding 8 and 5 -OH Nucleosides Bound to Solid Support, with DBU as the Catalyst... 

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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