ORGN 103 |
| A series of N-alkyl-N-alkyloxycarbonylaminomethyl and N-aryl-N-alkyloxy-carbonylaminomethyl derivatives of phenols and carboxylic acids were synthesized and their rates of hydrolysis investigated. Their rates of hydrolysis were found to be first order and were independent of the pH of the buffer from pH 4 to 8. The mechanism of hydrolysis is SN1 and it exhibits dependence on the pKa and nucleofugacity of the leaving group. The N-aryl-N-alkyloxycarbonylaminomethyl derivatives of phenols and carboxylic acids were chemically more stable and exhibited lower rates of hydrolyses compared to the N-alkyl-N-alkyloxycarbonylaminomethyl derivatives. N-Alkyl-N-alkyloxycarbonylaminomethyl derivatives of phenols were found to be enzymatically labile and thus can act as chemically stable prodrugs of phenolic drugs. N-Alkyl-N-alkyloxycarbonylaminomethyl derivatives of carboxylic acids are chemically very labile but their stability can be enhanced by using the N-aryl-N-alkyloxycarbonylaminomethyl promoiety which makes these derivatives sufficiently stable for possible formulation yet labile enough for them to be useful prodrugs of carboxylic acids.
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Asymmetric Reactions and Syntheses, Physical Organic Chemistry, Combinatorial Chemistry, Total Synthesis
8:00 PM-10:00 PM, Sunday, 26 March 2006 Georgia World Congress Center -- Ex. Hall B4, Poster
Division of Organic Chemistry |