Chiral phosphate configuration assignments

Despite the broad utility of chiral phosphorothioates, certain enzymes, such as alkaline phosphatase and phosphoglycerate mutase, do not accept phosphorothioates as substrates. Stereochemical studies of these enzymes awaited the development of methods to synthesize and assign configurations to chiral phosphates. Chiral [l60, l70,180]phosphomonoesters and [l8OJphosphodiesters have been elegantly... 

Draw a Fischer projection of sn-glycerol 1-phosphate, and assign R or S configuration to the chirality center. Do the same for sn-glycerol 2,3-diacetate. 

The first account of the synthesis of an oxygen chiral phosphate monoester was reported in 1978 by Knowles and co-workers (Abbott et ai, 1978, 1979). This ester, a diastereomer of l-phospho-(5)-1,2-propanediol, was selected as the synthetic target because the general method of configurational analysis that Knowles devised for monoesters was based on the ability to assign the configuration of the diastereomers at phosphorus of this particular phosphate monoester. The chemical steps in this synthesis are shown in Fig. 1. Briefly, [ OJPOCls, prepared in hi yield from and... 

Chemical modification may also simply be achieved by complex formation with an optically active agent191. For example, the correlation of the configuration of chiral non-racemic phosphate triesters, such as 11 (see p 417)11, with the relative (when compared with ent- ) change in H chemical shift of the methoxy doublet induced by the addition of Eu(hfc)3192 has been used for the assignment of absolute configuration of optically active phosphate triesters (chiral at phosphorus), which were obtained by asymmetric synthesis as indicated. 

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