Guanidines are a familiar functional group due to their presence in the amino acid arginine. Biochemically, the guanidine found in arginine can undergo oxidation via nitric oxide (NO) synthase to produce nitrosoarginine. This reactive species is inherently unstable and its decomposition pathways give rise to a variety of biochemical processes. If trapped by water, nitrosoguanidines hydrolyze to form ureas and release nitroxyl (HNO). Due to this instability, it is proposed that nitrosoguanidines trapped as Diels-Alder adducts of 1,3-dienes could be a suitable prodrug strategy. Upon the cycloreversion under biological conditions, hydrolysis could liberate urea-based pharmaceuticals along with nitroxyl, a biologically-active vasodilator and vasorelaxant. This study focused on the synthesis of various N-monosubstituted and N,N′-disubstituted nitrosoguanidine Diels-Alder adducts and monitoring their retro Diels-Alder reactions by 1H-NMR spectroscopy in a mixture of DMSO-d6 and D2O against an internal standard. This study constitutes the first systematic effort at assessing the effects of nitrosoguandine substitution on the retro-nitroso-Diels-Alder reaction.

N-substituted nitrosoguanidine Diels-Alder adducts: Synthesis and substituent effects on the rates of retro-Diels-Alder reactions

253rd National Meeting (2017)

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