Three pairs of alkaloid enantiomers from the root of Isatis indigotica

Three pairs of enantiomerically pure alkaloids with diverse structure features, named isatindigoticoic acid A and epiisatindigoticoic acid A [(−)-1 and (+)-1], phaitanthrin A and epiphaitanthrin A [(−)-2 and (+)-2], and isatindopyrromizol A and epiisatindopyrromizol A [(−)-3 and (+)-3], respectively, were isolated from an aqueous extract of the roots of Isatis indigotica. Racemic and scalemic mixtures of these enantiomers were separated by HPLC on a chiral semi-preparative column. Their structures including absolute configurations were determined by extensive spectroscopic analysis in conjunction with the calculation of electronic circular dichroism (ECD) spectra. The enantiomer pairs possess parent structures of 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic acid, indolo[2,1-b]quinazolinone, and 3-thioxohexahydro-1H-pyrrolo[1,2-c]imidazol-1-one, respectively. Except for phaitanthrin A [(−)-2] which the configuration was previously undetermined, these compounds are new enantiomeric natural products.

Graphical abstractThree pairs of alkaloid enantiomers (−)-/(+)-1−(−)-/(+)-3, having parent structures of 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic acid, indolo[2,1-b]quinazolinone, and 3-thioxohexahydro-1H-pyrrolo[1,2-c]imidazol-1-one, respectively, were isolated from a Chinese traditional herbal medicine “ban lan gen” (Isatis indigotica roots). Their absolute configurations were determined by comparison of experimental CD and calculated ECD spectra. Separation of these racemic and scalemic mixtures indicates that I. indigotica is an uncommon plant to produce diverse enantiomeric natural products, providing a fertile area for further inquiry for biogenetic mechanisms to create distinctive enantiomers, as well as for chemical synthesis and in-depth biological evaluation.Figure optionsDownload full-size imageDownload as PowerPoint slide