The structural and conformational analyses and antioxidant activities of chebulinic acid and its thrice-hydrolyzed derivative, 2,4-chebuloyl-β-D-glucopyranoside, isolated from the fruit of Terminalia chebula

Abstract

Tri-O-galloyl-2,4-chebuloyl-β-D-glucopyranoside (chebulinic acid, 1) and its novel thrice- hydrolyzed derivative, 2,4-chebuloyl-β-D-glucopyranoside (galloyl-free chebulinic acid, 2), together with ellagic (3) and gallic acids (4), ethyl gallate (5), and luteolin (6), were isolated from the dried fruit of Terminalia chebula by bioactivity-guided fractionation of the extract. The compounds were variously identified on the basis of UV, MS, and NMR data. The latter proved that the glucose unit in 1 adopts a well defined 1 C4 chair conformation with all substituents in axial positions. However, the absolute configurations of the three stereocenters in the chebuloyl group have been reassigned. For 2, a solvent-dependent mixture of both open-chain and cyclic pyranose forms was observed, the latter with a β configuration for the anomeric C-1 sugar carbon being heavily preferred in aqueous solution. In contrast to 1, a dynamic equilibrium consisting of several possible skew conformers ( 5 S1, 1 S5, 1 S3, and 2 SO) was designated for the sugar ring of 2. Antioxidant activities of the isolated compounds were assessed by measuring their ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and to inhibit the autoxidation of methyl linoleate in vitro. Of the isolated compounds, 1 showed the highest radical scavenging activity in the DPPH assay. For the methyl linoleate assay, 2 and 4−6 all exhibited strong antioxidant activities whereas the activities of 1 and 3 were only moderate. The fruit extract itself was highly effective in both tests.