SYNTHESIS AND REACTIONS OF A CHEMICAL-MODEL OF THE UROCANASE REACTION

Using a convergent synthetic strategy starting from nicotinic acid and imidazole, we have prepared the (E) and (Z) isomers of 1-(p-tolylsulf amoyl)imidazol-4-yl)ethyl]pyridinium bromide (21) as models of the uro canase reaction. Domino reactions of both (E)-21 and (Z)-21 led to the same spirocyclic compound, H-furo[2,3-g]imidazo[5,4-f]isoquinolyl]car boxamide (33), which was isolated and spectroscopically characterised. A possible sequence of reactions leading to 33 shows a number of anal ogies to the conversions catalysed by the enzyme urocanase. Removal of the p-tolylsulfamoyl protecting group of(E)-21 and (2)-21 under mild conditions led to the highly reactive model compounds (E)-4 and (Z)-4, which were identified by H-1 NMR spectroscopy, but could not be isola ted, owing to their instability. To facilitate the monitoring of the r eaction cascade by NMR spectrocopy (2)-21 was prepared in which the be nzyl group was fully deuterated. Its deprotection to (2)-4 started a r eaction cascade, which led, after purification, to a main product. Acc ording to investigations by UV and H-1 NMR spectroscopy it seems very likely that 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.