Abstract: AIM:To discover more active and water-soluble derivatives of tetracyclic diterpenoids containing an exo-methylene cyclopentanone or an α-methylenelactone moiety.METHODS:All of the key intermediates were synthesized from stevioside,and the target compounds were obtained through glycosylation of the 4-carboxyl group.The cytotoxicity of the target compounds against six human cancer cell lines,HepG2,Bel-7402,A549,U251,MCF-7 and MDA-MB-231,were evaluated by the MTT assay.RESULTS:Compound 1b was more effective than the positive control adriamycin against the HepG2,Bel-7402,A549,MCF-7,and MDA-MB-231 cell lines with IC50 values of 0.12,0.91,0.35,0.08,and 0.07 μmol·L-1,respectively.Moreover,compound 3c exhibited the most potent and selective cytotoxic activity against the HepG2 cell line(IC50,0.01 μmol·L-1).CONCLUSION:Compounds 1b and 3c could be considered as potential anticancer candidates for further study.