New Entries in Organocatalysts\nfrom an Alkaloid Library;\nDevelopment of Aminal Catalysis for a Michael Reaction Based on Calycanthine

Natural products have historically been actively evaluated\nfor\ntheir biological activity in the development of pharmaceuticals, while\ntheir evaluation as asymmetric catalysts has rarely been explored.\nIn this study, we evaluated the catalytic activity of the natural\nproduct library. Three naturally occurring alkaloids, gardnerine,\nspiradine A, and calycanthine, were found to catalyze an asymmetric\nMichael reaction using oxindole and nitrostyrene. We further studied\n(+)-calycanthine, which is characterized by its aminal structure.\nConcise synthetic and extraction protocols were developed to provide\nboth enantiomers of calycanthine. Further derivatization of this alkaloid\nled to improved enantioselectivity in a model reaction. Computational\nstudies suggested that the aminal moiety of the catalyst activated\nnucleophiles and electrophiles through multiple hydrogen bonding interactions,\nincluding nonclassical hydrogen bonds between carboxylic acid and\nthe aminal C–H.