a b s t r a c tWe have previously reported enantioselective reactions of 1,3-diketones and b-ketoesters with various electrophiles catalyzed by chiral Pd complex, in which chiral Pd enolates play a key role. Here, we present a detailed examination of Pd-catalyzed enantioselective Michael addition and fluorination reactions of bketoamides. b-Ketoamide showed higher reactivity than 1,3-diketone and b-ketoester, though its aproton is likely to be least acidic. Pd enolate formation of b-ketoamide was much faster than that of bketoester. The crystal structures of (R)-BINAP-Pd-diketone and ketoamide complexes were found to be quite distinct. Pd-diketone complex has bidentate square-planar geometry as have been predicted before, whereas Pd-ketoamide complex was greatly distorted, probably due to steric constraints of the amide bond.

Modification of our previously reported selective inhibitor of oxidative stress-induced necrosis, 2-(1H-indol-3-yl)-3-pentylamino-maleimide (IM-54) by regioselective reduction of the C-4 carbonyl group afforded a 3-amino-2-indolyllactam (IL-1) with more potent activity. To examine the structure-activity relationship of IL derivatives, we developed new synthetic routes with flexibility to incorporate a range of substituents at a late stage. The synthesized IL derivatives were evaluated for activity to inhibit necrotic cell death induced by hydrogen peroxide. Among them, IL-12 showed the most potent activity (IC 50 49 nM) among the IL and indolylmaleimide (IM) derivatives examined.

A solid-supported palladium complex successfully captured β-ketoamide-tagged peptides as palladium enolates and released them in high yield upon acid treatment.