Guanidino-aryl substituted enol lactones: Selective and potent mechanism-based inhibitors of trypsin-like serine proteases
Two classes of valero enol lactones were synthesized and examined as potential inhibitors of trypsin-like serine proteases. The first class of protio and iodo enol lactones had either a 4-guanidino phenyl substituent (3-(4-guanidinophenyl)-6-methylidene tetrahydro-2-pyranone (1) and 3-(4-guanidinophenyl)-6-(E)-iodomethylidene tetrahydro-2-pyranone (2)) or a 4-guanidinomethyl phenyl substituent (3-(4-guanidinomethylphenyl)-6-methylidene tetrahydro-2-pyranone (3) and 3-(4-guanidinomethylphenyl)-6-(E)-iodomethylidene tetrahydro-2-pyranone (4)) at the $\alpha$-position. The $\beta$-aryl substituted system included the 4-guanidino phenyl substituted protio and iodo enol lactones 4-(4-guanidinophenyl)-6-(methylidene) tetrahydro-2-pyranone (5) and 4-(4-guanidinophenyl)-6-(E)-iodomethylidene tetrahydro-2-pyranone (6), as well as the corresponding $\alpha$-benzamido substituted analogs (3R*,4R*) 3-benzamido-4-(guanidinophenyl)-6-methylidene tetrahydro-2-pyranone (7) and (3R*,4R*) 3-benzamido-4-(4-guanidinophenyl)-6(E)-iodomethylidene tetrahydro-2-pyranone (8).
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