Epicatechinoceanothic acid A and B, novel catechin-bonded ceanothane-type triterpenoids isolated from roots of Ziziphus jujuba

Abstract

Ziziphus jujuba Mill. (Rhamnaceae) is a 5 m tall deciduous tree, widely cultivated in southern Europe and Asia including India, Russia, the Middle East and China. In Korea, fruits and seeds of this plant have been used as food and traditional remedies for insomnia. Hundreds of compounds including triterpenic acids, flavonoids, phenolic acids and cyclopeptide alkaloids have been isolated and reported from Z. jujuba. However, chemical constituents of the roots have been rarely studied, compared to ones of other plant parts of this plant. In our investigation for novel bioactive constituents from the roots of Z. jujuba, we separated two structurally novel ceanothane-type triterpenoids. These two triterpenoids were containing an epicatechin moiety in their molecular structures, so they were named epicatechinoceanothic acid A (1) and B (2), after their structural characters. Additionally, three known compounds, ceanothic acid (3), epiceanothic acid (4) and (-)-epicatechin (5) were also separated and referred for the structural elucidation of 1 and 2. Planar structures of 1 and 2 were determined by 1D, 2D NMR and MS spectra. Configurations of these compounds were suggested by ROESY NMR spectra, but there were still unsolved issues, such as the configurations of the epicatechin moieties. For configurational elucidation, molecular modelling method was applied. By comparing computational optimized structures of possible candidates with the ROESY NMR spectra data, the configurations of two epicatechinoceanothic acids were confirmed. 1, 3 and 4 were subjected to bioactivity screening (2 was excluded because of its small quantity), and 1 was evaluated to be a potent inhibitor of the signal transducer and activator of transcription-3 (STAT3) pathway in the human malignant glioma U87-MG cells.