Two pairs of unusual scalemic enantiomers from Isatis indigotica leaves

Two pairs of unusual scalemic enantiomers with a novel carbon skeleton of 2-[1'-(4"-hydroxy-3",5"-dimethoxyphenyl)ethyl]-2-methoxyindolin-3-one, named isatidifoliumindolinones A-D (1-4), were isolated from an aqueous extract of Isatis indigotica leaves (da qing ye). Their structures including absolute configurations were determined by spectroscopic data analysis combined with comparison of their experimental CD and calculated ECD spectra. Validity of the ECD spectra calculation to assign the absolute configurations is discussed. Plausible biosynthetic pathways of 1-4 are proposed. Stereochemistry-dependent activity against LPS-induced NO production in BV2 cells was observed, and among the stereoisomers compound 4 is most active.