Six scalemic mixtures of 6-monosubstituted dihydrobenzophenanthridine alkaloids from Chelidonium majus and optically active structures of enantiomers

Abstract

Six pairs of previously undescribed 6-monosubstituted dihydrobenzophenanthridine alkaloids were separated as corresponding six scalemic mixtures from the aerial part of Chelidonium majus. The elucidation for the 2D structures of these alkaloids was achieved using regular spectroscopic and chemical methods. The assignment of scalemic-mixture nature was achieved using combined examinations of their NMR data, CD spectra, calculation of specific rotations, and chiral HPLC profiles. The identification for the relative configurations of alkaloids possessing two asymmetric carbons directly connected up by a rotatable sp3-sp3 carbon-carbon single bond was significantly facilitated by discussing the erythro and threo relative configurations defined by the mutuality of the orders of decreasing steric hindrances between the two sets of ligands linked to the two chiral centers. Two scalemic mixtures were assigned as (1′R,6R/1′S,6S)- and (1′S,6R/1′R,6S)-1-(dihydrochelerythrine-6-yl)ethanols, two as (1′R,6R)/(1′S,6S)- and (1′S,6R)/(1′R,6S)-1-(dihydrosanguinarine-6-yl)ethanols, one as (±)-ethyl 2-(dihydrosanguinarine-6-yl)acetate, and one as (±)-ethyl dihydrosanguinarine-6-carboxylate, respectively. The resolution of three scalemic mixtures was achieved and the absolute configurations of the three pairs of enantiomers were assigned via time-dependent Density Functional Theory calculations of electronic circular dichroism (ECD) data. The assignment for the absolute configurations of the other three scalemic mixtures was achieved via a chiral HPLC-UV/CD method plus analyzing their ECD data. The findings of this paper demonstrated that the relevant biochemical reactions concerning the construction of these 6-monosubstituted dihydrobenzophenanthridine alkaloids in the test plant are very nonselective. Scalemic mixture of (1′R,6R)/(1′S,6S)-1-(dihydrosanguinarine-6-yl)ethanol exhibited biological activity. It inhibited the growth of human MDA-MB-231 cell line at a moderate level with IC50 value of 5.12 μM.