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Synthesis and Reactions of a Chemical Model of the Urocanase Reaction
Author(s) -
Winter Joachim,
Rétey János
Publication year - 1997
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.19970030312
Subject(s) - chemistry , bromide , nuclear magnetic resonance spectroscopy , pyridinium , imidazole , benzyl bromide , medicinal chemistry , stereochemistry , cascade reaction , reaction mechanism , catalysis , organic chemistry
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.