Absolute configuration of (+)-[fluoro(hydroxyphenylphosphinyl)methyl]-phosphonic acid, a specific inhibitor of Na(+)-gradient-dependent Na(+)-phosphate cotransport across renal brush border membrane, by X-ray crystallographic analysis of its (-)-quinine salt.
Racemic [fluoro(hydroxyphenylphosphinyl)methyl]phosphonic acid (1) and its individual enantiomers [(+), 98% ee; (-), 67% ee] were previously shown to inhibit Na(+)-gradient-dependent Na(+)-phosphate cotransport across renal brush border membrane, without measurable stereospecificity. Resolution of 1 was effected by fractional recrystallization of its (-)-quinine salts. The more levorotatory, diquinine product 2, corresponding to (+)-1, has now been analyzed by X-ray crystallography and found to be composed of the S enantiomer of 1. This result confirms the absence of stereochemical preference in inhibition of the cotransporter by the enantiomers of 1 and provides the first absolute configuration assignment of an asymmetrical alpha-halomethylene pyrophosphate analogue.
Bau
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Department of Chemistry, University of Southern California, Los Angeles 90089-0744, USA.
Pham
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Duncan
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McKenna
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D002352:Carrier Proteins / Q000187:drug effects*; D018360:Crystallography, X-Ray; D004164:Diphosphonates / Q000737:chemistry* / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D008968:Molecular Conformation; D011803:Quinine / Q000737:chemistry; D012492:Salts; D012964:Sodium / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters
C093436:(fluoro(hydroxyphenylphosphinyl)methyl)phosphonic acid; D002352:Carrier Proteins; D004164:Diphosphonates; D012492:Salts; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D012964:Sodium; D011803:Quinine