Primary amine diazeniumdiolates have emerged as new pH-dependent donors of nitroxyl,1 a potential therapeutic agent for treating congestive heart failure. Preparing primary amine diazeniumdiolate salts generally pose significant challenge on account of low thermodynamic stabilities. We report a novel dehydrohalogenation-based synthesis for preparation of caged methylamine diazeniumdiolates (MA/NO) starting with O2-derivatized RR'N-N(O)-N-OR? as a synthon. Caged MA/NO analogs exist as dynamic equilibrium mixture of Z- and E-isomeric forms in solution, first ever reported in an acyclic system. Crystallographic identification of Z-conformer, determination of pKa, and pH-dependent fluxional behaviour of isomeric mixtures has been studied. Cytochrome P450-mediated metabolism of O2-benzyl analog and HNO/NO release profile of several MA/NO analogs have been reported augmenting their development as potentially new HNO/NO prodrugs of diazeniumdiolate origin.Reference:Andrei et al J. Am. Chem. Soc. 2010  , 132, 16526-16532.

O<sup>2</sup>-Functionalized methylamine diazeniumdiolates as potential nitroxyl prodrugs

244th National Meeting (2012)

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O2-Functionalized methylamine diazeniumdiolates as potential nitroxyl prodrugs

O²-Functionalized methylamine diazeniumdiolates as potential nitroxyl prodrugs