Thiophosphate esters, synthesis

A sensitive probe applied to understand the nature of the reaction mechanism of group transfer is the stereochemistry of the overall reaction. The reaction at a phosphoryl center normally is a degenerate question, since a monosubstituted phosphate ester or anhydride is proprochiral at the phosphate center. Phosphate centers at a diester or disubstituted anhydride are prochiral. Two related methods to analyze the stereochemistry at a phosphate center have been developed by the generation of chirality at the phosphorus center. The first approach was developed by Usher et al. (24) and gave rise to the formation of isotopi-cally chiral [ 0, 0]thiophosphate esters and anhydrides (I). Isotopically chiral [ 0, 0, 0]phosphates (II) have also been synthesized and the absolute configurations determined. Two primary problems must first be addressed with respect to both of the methods that have been developed the synthesis of the isotopically pure chiral thiophosphates and phosphates and the analysis of the isotopic chirality of the products. An example of the chiral starting substrates, as developed for ATP, is schematically demonstrated. Ad = adenosine. 

Further developments in the. synthesis of phosphate and thiophosphate esters from myo-inositol (10) have been widely described. By and large, these syntheses have followed the procedures and used reagents (particularly with regard to the nature of protection... 

Inch and his co-workers continue to use carbohydrate derivatives in the synthesis of chiral esters of phosphorus acids and for studies of the displacement reactions of these esters. For example, the tetrahydro-l,3,2-oxazaphosphorine-2-ones (74) and (76) were synthesized and cleaved to give the chiral phosphonate (75) and the chiral phosphate (77), as illustrated in Schemes 35 and 36. 2-Thiones related to (74) and (76) were also prepared and used to obtain such chiral thiophosphates as (78) from (79). Attack on the acyclic S -methyl phos-... 

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