posted on 2020-03-20, 15:38authored byNabeelah
I. Kauser, Mark Weisel, Yong-Li Zhong, Michael Man-Chu Lo, Amjad Ali
The
therapeutic application of nitric oxide, an endogenous cellular
signaling molecule, has been limited due to the difficulty of developing
stable pro-drugs with slow kinetics of NO release. Diazeniumdiolates
are valuable NO donors; however, synthetic challenges have hampered
their use. O2-alkylation or arylation of diazeniumdiolates
form stable pro-drugs which have found application in hypertension,
cancer, and as antimicrobial agents. The synthesis of sodium diazeniumdiolates
has proven to be challenging due to hazardous reaction conditions
(high N2O concentrations, and flammable solvents), which
can lead to detonation and suffered from limited scope. We have previously
disclosed that synthesis of calcium diazeniumdiolate salts are a safer
and more scalable alternative. Herein, we report the expanded scope
of calcium diazeniumdiolates from benzylic amines, amides, and sterically
bulky amines hitherto inaccessible and a comparison of their reactivity
in comparison to sodium diazeniumdiolate.