Synthesis and biological evaluation of novel exo-methylene cyclopentanone tetracyclic diterpenoids as antitumor agents.

The structure of exo-methylene cyclopentanone, which exists in nature tetracyclic diterpenoids products, has been proved to be an innate group for the treatment of cancer and inflammation. In this letter, four different scaffolds of tetracyclic diterpenoids including the structure exo-methylene cyclopentanone were synthesized from steviol and isosteviol and evaluated in vitro for their antitumor activity against three human cancer lines. Compounds 1a, 1b, 2b and 3b showed significant cytotoxicity, particularly, tetracyclic diterpenoids 2b, 3b were identified as the most potent and selective anticancer agents superior to adriamycin with IC(50) values of 0.9 μM and 1.5 μM, against Hep-G2 and MDA-MB-231 cell lines, respectively.