Abstract
Using a convergent synthetic strategy starting from nicotinic acid and imidazole, we have prepared the (E) and (Z) isomers of 1‐benzyl‐3‐carbamoyl‐5‐[2‐(ethoxycarbonylmethylene)‐2‐(1‐(p‐to‐lylsulfamoyl)imidazol‐4‐yl)ethyl]pyridinium bromide (21) as models of the urocanase reaction. Domino reactions of both (E)‐21 and (Z)‐21 led to the same spirocyclic compound, (3aRS)‐11‐[9‐([D~7~]benzyl)‐5‐ethoxy‐1‐(p‐tolylsulfamoyl)‐1__H__,9__H__‐furo[2,3‐g]imidazo[5,4‐f]isoquinolyl]carboxamide (33), which was isolated and spectroscopically characterised. A possible sequence of reactions leading to 33 shows a number of analogies to the conversions catalysed by the enzyme urocanase. Removal of the p‐tolylsulfamoyl protecting group of (E)‐21 and (Z)‐21 under mild conditions led to the highly reactive model compounds (E)‐4 and (Z)‐4, which were identified by ^1^H NMR spectroscopy, but could not be isolated, owing to their instability. To facilitate the monitoring of the reaction cascade by NMR spectroscopy (Z)‐21 was prepared in which the benzyl group was fully deuterated. Its deprotection to (Z)‐4 started a reaction cascade, which led, after purification, to a main product. According to investigations by UV and ^1^H NMR spectroscopy it seems very likely that 1‐([D~7~]benzyl)‐3‐carbamoyl‐7‐(ethoxycarbonylmethyl)‐imidazo[4,5‐f]isoquinolinium bromide (27) was formed. The presumed mechanism of its formation again shows similarities with the postulated mechanism of action of urocanase.