Reactions of Nitric Oxide with Beta-Hydroxylimino Esters

Nitric oxide (NO) and its one electron reduction product nitroxyl (HNO) are known to act as vasodilators in mammals, including humans, and are considered a possible cure to cardiovascular diseases. However, their instability and high reactivity with atmospheric oxygen preclude the direct use of them as drugs. Recent work has shown that NO donor molecules can be used as pro-drugs to deliver NO to the appropriate bio-sites. Therefore, there is considerable research interest in the synthesis and studies of donors capable of releasing either of the molecules under physiological conditions. As part of our research effort towards the synthesis of new NO- and HNO-donors, we have synthesized new nitroxy derivatives from the reaction of two b-hydroxylimino esters namely, methyl 3-hydroxyliminobutanoate and methyl 3-hydroxyliminopentanoate, with potassium hydroxide and NO. The isolated products are characterized as potassium 3-methyl- and 3-ethyl-5-isoxazolone-4-diazeniumdiolate, as well as potassium 4-acetyltriazolium-1,2,3-triolate. The new diazeniumdiolates are first examples of diazeniumdiolate-substituted isoxazolone. Under modified conditions, the reactions yield the potassium salts of 5-acetyl- and 5-propionylsydnonate-N-oxides.