Enzyme-catalyzed domino reaction: efficient construction of spirocyclic oxindole skeleton using porcine pepsin†
Abstract
Pepsin from porcine gastric mucosa was used as a sustainable and environmentally friendly biocatalyst in the domino Knoevenagel/Michael/Michael reaction for the synthesis of spirooxindole derivatives in methanol. A wide range of isatins and α,β-unsaturated ketones reacting with malononitrile provided the corresponding products in yields of up to 99% with diastereoselectivities of up to >99 : 1 dr. This pepsin-catalyzed domino reaction provided a novel case of enzyme catalytic promiscuity.