Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
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-([D7]benzyl)-5-ethoxy-1-(p-tolylsulfamoyl)-1H,9H-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 1H 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 1H NMR spectroscopy it seems very likely that 1-([D7]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.
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