Sulfur-phosphorus linkages

With respect to stereochemistry, substitution of one unbonded oxygen atom of the proch-iral phosphorus linkage in an oligonucleotide by sulfur, nitrogen or borane creates a chiral center leading to diastereomeric mixtures of RP and SP compounds in synthesis. Since the number of diastereomers increases by 2", this sums up to the formation of about half a million diastereomeric compounds during the synthesis of a 20-mer. Nevertheless, antisense activity remains intact in such diastereomeric mixtures. 

A nitrogen to carbon linkage is exemplified by the formation of dichloro-1,2,4-thiadiazole (27) from phosphorus tricyanide and sulfur dichloride.32... 

Benzopentathiepin 27 reacts with phosphorus ylides d-RCgPLtCP PPhjCl (R = MeO, Me, H, Cl, NO2) to form a mixture of benzotetrathiepins 28 and benzotrithiins 29 (Equation 3). The carbanion fragment of the phosphorus ylides replaced the one or two sulfur atoms in the multi-sulfur linkages of benzopentathiepin. Systematic desulfurization to form a new cyclic system was accomplished by the use of a combination of phosphorus ylide and triphenylphosphine in the reactions of benzopentathiepin, benzotetrathiepins, and benzotrithiins <1997H(44)187>. 

The activation mechanism of phosphosulfate linkages (P—O —S)has been studied to understand the chemistry of biological sulfate-transfer reactions of phosphosul-fates of adenosine (APS and PAPS). Several phosphosul-fates were prepared and subjected to several nucleophilic reactions including hydrolysis. In general, phosphosulfates are stable in neutral aqueous mediay but become labile under acidic conditions, resulting in selective S—O fission. This S—O fission appears to occur by unimolecular elimination of sulfur trioxide, which can react with a nucleophilic acceptor, leading to a sulfate-transfer reaction. This process can be accelerated by Mg2+ ion when the solvent is of low water content. Under neutral conditions, divalent metal ions also were found to catalyze nucleophilic reactions, but these occurred on phosphorus to result in exclusive P-O fission. 

Phosphorus-containing leaving groups with glycosyl-sulfur linkages such as dithiophosphates and phosphorodiamidimidothioates were discussed in Section 4.3.2.3. 

It has been found that when the mixture is heated at such a high temperature, a considerable amount of sulfur trioxide is expelled from the melt, while phosphorus pentoxide is not expelled. Chemical analyses of the reaction products revealed that 63.5 and 80.8% of the total sulfur was expelled as sulfur trioxide when prepared at 1300 or 1400°C., respectively. If one assumes that no compounds with S-O-P linkages are produced in the sample, the reaction can be represented by ... 

In order to determine the TP concentration in water, the digestion process must involve both oxidative and hydrolytic processes in order to hydrolyze P-O-P linkages (e.g., polyphosphates) and oxidize phosphoesters and C-P compounds to inorganic phosphate. For example, in an online TP digestion system, which involves both thermal digestion and UV photooxidation, it is necessary to use a mixture of sulfuric acid and peroxydisulfate in order to obtain high recoveries of both organic and condensed phosphorus. 

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