Burlingham, Benjamin T. Widlanski, Theodore S. Synthesis and Biological Activity of <i>N</i>-Sulfonylphosphoramidates:  Probing the Electrostatic Preferences of Alkaline Phosphatase <i>N</i>-Sulfonylphosphoramidates have been synthesized to investigate the electrostatic requirements for binding to alkaline phosphatase. Alkyl- and aryl <i>N</i>-benzylated sulfonamides were phosphorylated with bromophosphates or synthesized via phosphoramidite chemistry in moderate yields (44−77%.) The resulting tribenzylated <i>N</i>-sulfonylphosphoramidates may be deprotected in one step to give the free acids in quantitative yields. Physical data of <i>N</i>-sulfonylphosphoramidates, including p<i>K</i><sub>a</sub>'s and stability toward hydrolysis, were determined. Inhibition data suggests that AP does not bind trianionic <i>N</i>-sulfonylphosphoramidates better than dianionic <i>N</i>-sulfonylphosphoramidates, although <i>N</i>-sulfonylphosphoramidates are bound tighter than <i>N</i>-phenylphosphoramidate. <i>k</i><sub>cat</sub> for the hydrolysis of <i>N</i>-sulfonylphosphoramidates by bovine and <i>E. coli</i> alkaline phosphatases is 10−60% that of <i>p</i>-nitrophenyl phosphate. tribenzylated N;nitrophenyl phosphate;p K;sulfonylphosphoramidate;bind trianionic N;aryl N;dianionic N;Biological Activity;benzylated sulfonamides;Physical data;AP;Inhibition data;Electrostatic Preferences;Alkaline Phosphatase N;phosphoramidite chemistry;k cat 2001-08-21
    https://acs.figshare.com/articles/journal_contribution/Synthesis_and_Biological_Activity_of_i_N_i_-Sulfonylphosphoramidates_Probing_the_Electrostatic_Preferences_of_Alkaline_Phosphatase/3689763
10.1021/jo010495q.s001