Development of N-Substituted Hydroxamic Acids with Pyrazolone Leaving Groups as Nitrosocarbonyl Precursors.
A novel class of nitrosocarbonyl precursors, N-substituted hydroxamic acids with pyrazolone leaving groups (NHPY), has been synthesized. Under physiological conditions, these compounds generate nitrosocarbonyl intermediates, which upon hydrolysis release nitroxyl (azanone, HNO) in excellent yields. The amount and rate of nitrosocarbonyl generation are dependent on the nature of the pyrazolone leaving groups and significantly on the structural properties of the NHPY donors. Pyrazolones have been found to be efficient nitrosocarbonyl traps, undergoing an N-selective nitrosocarbonyl aldol reaction. This trapping reaction has been used to confirm the involvement of nitrosocarbonyl intermediates in NHPY aqueous decomposition. In addition, NHPY compounds are shown to generate nitrosocarbonyls efficiently under mild basic conditions in organic solvent and may therefore also enjoy synthetic utility.
Department of Chemistry, Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
Saghar
S
Nourian
Department of Chemistry, Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
Zachary A
ZA
Zilber
Department of Chemistry, Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
John P
JP
Toscano