Organic compounds -- part of the class 532-570 series – Organic compounds – Phosphorus esters
Patent
1999-07-13
2000-11-14
Ambrose, Michael G.
Organic compounds -- part of the class 532-570 series
Organic compounds
Phosphorus esters
558161, C07F 940
Patent
active
06147245&
ABSTRACT:
A unique method for the synthesis of substantially pure .alpha.-keto bisphosphonate esters and the usage of these esters in reactions with C, N, O, or P nucleophiles for synthesis of .alpha.-functionalized bisphosphonates. The method starts with a reaction mixture formed of an .alpha.-diazo methanediphosphonate ester, including tert-butylchlorite, a polar aprotic organic solvent, and an effective amount of water. After synthesis is complete, a water trapping reagent may be added to remove any excess water. The present invention provides a versatile pathway to new .alpha.-substituted bisphosphonate derivatives and could be readily adapted to combinatorial drug discovery synthetic strategies. The .alpha.-keto bisphosphonate esters can be converted to the corresponding acids by acid hydrolysis or mild silyldealkylation.
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Kashcmirov Boris A.
McKenna Charles E.
Ambrose Michael G.
University of Southern California University Park
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