Phosphorothioates, stereospecific synthesis

With regard to the phosphorus stereochemistry, a new stereospecific synthesis of chiral 0,0-dialkyl thiophosphoric acids (6,7) has been developed which is based on the Horner-Wittig reaction of the optically active phosphonothionate carbanions containing the sulfoxide or dithioacetal moieties. The transformation of (R)-(+) 0-methyl 0-isopropyl methanephosphonothionate (10)(8) into (R)-(-) 0-isopropyl phosphorothioic acid (H) best Illustrates this method. 

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... 

Picoline 77-oxide was used as an intramolecular catalytic group to secure stereochemical integrity of the phosphorus center in a stereospecific synthesis of dinucleoside phosphorothioate diesters <04CC290>. 

Oligonucleotides containing phosphorothioate intemucleoside linkages (122) have been of interest for several years now. Full details describing the stereospecific synthesis of phosphorothioates using the oxathiaphospholane monomers... 

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... 

The chiral y-[l80]phosphorothioate of ATP, (Pp)-ATPyS, yl80(/3, y)lsO, was synthesized by the procedure outlined in Fig. 8 [25]. (Sp)-ADPaS, alsO(a,/3)l80 was prepared by stereospecific phosphorylation of AMPaS, al802 using the adenylate and pyruvate kinase system followed by dephosphorylation with glucose and hexokinase. This was the starting material for the synthesis, with the chiral a-... 

A crucial point in the synthesis of optically pure dinucleoside phosphorothioates is the separation of the precursors of the final products that differ only in their configuration around phosphorus. Column chromatography on silica gel is an efficient and convenient way to separate the diastereomers of H-phosphonate diesters. The results obtained reveal that the sulfurization of suitable protected diribonucleoside H-phosphonates with elemental sulfur is a stereospecific reaction, which is most likely proceeding with the retention of the configuration at the phosphorus center. 

Lesnikowski, Z J and Jaworska, M M (1989) Studies on stereospecific formation of p-chiral internucleotide linkage. Synthesis of (Rp,Rp)-annitro-benzyl group as a new S-protection Tetrahedron Lett. 30,3821-3824... 

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