Stereocontrolled transformations of organophosphorus acid esters

A variety of phosphoric acid triesters and their derivatives are used as pesticides. Although there are no natural phosphorotriesters, those artificial ones undergo decomposition in the soil, implying that some microorganisms exist which are capable of hydrolysing them. The first report on a stereoselective enzymatic phos-photriester hydrolysis was pubhshed in 1973, when Dudman and Zerner succeeded 

Phosphotriesterase from P. diminuta (PTE) was found to exhibit high hydrolytic activity towards various types of tetracoordinated phosphorus acid esters. Apart from the phosphonothionate 92, phosphoric acid triesters 94 (Equation 45), ° benzenephosphonic acid diester 95 (Equation 46) ° and methyl-phenylphosphinic acid ester 96 (Equation 47) were also stereoselectively hydrolysed under kinetic resolution conditions. Of course, in the case of the latter three kinds of substrates, half of the reacting ester was irreversibly lost due to the formation of achiral phosphorus acids. 

In the case of the phosphotriesters 94, the use of engineered mutants of phosphotriesterase allowed not only to enhance but even to reverse the stereoselectivity of the native enzyme. The ees of the recovered esters exceeded 95%. 

In turn, for the phosphonic acid diester 95, stereoselectivity of the native phosphodiesterase was enhanced by over three orders of magnitude by alteration of the pA a values of the leaving group phenol. Eor example, for X = C02Me, Y = H the stereoselectivity was 5000 higher than for X = NO2, Y = 2-F.  

Both types of manipulation were applied to achieve the required enantiomer and the highest enantioselectivity in the hydrolysis of the phosphinic acid diester 

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