Papain as a sustainable and inexpensive biocatalyst was used for the first time to catalyze the Knoevenagel
reactions in DMSO/water. A wide range of aromatic, hetero-aromatic and a,b-unsaturated aldehydes
could react with less active methylene compounds acetylacetone and ethyl acetoacetate. The
products were obtained in moderate to excellent yields with Z/E selectivities of up to 100:0. This case of
biocatalytic promiscuity not only widens the application of papain to new chemical transformations, but
also could be developed into a potentially valuable method for organic synthesis