Unusual glycosidic labdane diterpenoids with cytotoxicity from the root of Phlomoides betonicoides

Chemical investigation on the root of Phlomoides betonicoides led to the isolation of six undescribed diterpenoid glycosides, phlomoidesides A-F, along with two known ones using various chromatographic techniques. The structures of these compounds were determined by extensive spectroscopic analyses (including 1D, 2D-NMR and HRMS), single crystal X-ray diffraction, and calculated C-13 NMR. The glycoside modifications of phlomoidesides A-F are rare in natural products, and a plausible biosynthetic pathway for these unusual glycosides was proposed. Phlomoidesides A, D, F, and phlomisosides V,III were cytotoxic against three human tumor cell lines, NCI-H1975, HepG2 and MCF-7, with IC50 values ranging from 7.5 to 75.7 mu M. Phlomoideside B only showed weak cytotoxicity against NCI-H1975, with IC50 of 53.0- mu M.