These diterpenes (1) and (2) were synthesized via epoxidation and rearrangements of (-)-Kaur-9(11), 16-dien-19-oate (7) isolated from Venezuelan species of espeletia (frailejón), and their antimicrobial and antitumoral activity were evaluated. Compound (1) showed GI 50 values of 51.6 nM against CNS SF-539, LC 50 = 100 µM, log 10 GI 50 = -7.29; compound (2) showed GI 50 at 4.17 µM against breast cancer T47D, LC 50 = 39 µM and Log 10 GI 50 = -5.38. Our results suggest that these compounds are highly cytotoxic and cytostatic against human cancer cell lines.

The synthesis of optically active trinorditerpenes was carried out, and their antimicrobial and antitumor activity was tested. The synthetic derivative 12-hydroxypodocarpa-8,11,13-triene (7) showed GI 50 at 6.6 µM against breast cancer . 11, showed GI 50 at 12.1 µM against leukemia RPMI-8226 (LC 50 = 76.1 µM and log 10 GI 50 = -4.92).Key words: trinorditerpenoid derivatives, antimicrobial and cytotoxic activity.The trinorditerpenes have attracted the interest of natural product chemists during the past decades. In this context, simple and sequential modifications were performed on the methyl O-methylpodocarpane molecule (1) because it is a chiral starting material for the synthesis of diterpenoids with biological activity [1-3]. Our goal was to make this class of trinorditerpenoids readily available for the investigation of the basic structural requirements to explore the antimicrobial and antitumor activity.The compounds synthesized by us were evaluated for their antimicrobial activity in a preliminary screening. We observed that the compound 7 showed activity against Gram-positive bacteria, Gram-negative bacteria, yeast, and mold (Table 1). This particular antimicrobial ability attracted our attention to the compound 7 since it has a more simple structure than the other compounds reported here. Of the eight compounds reported here, four were accepted and tested at the National Institute of Health (NIH), Developmental Therapeutics Program (DTP), to evaluate the antitumor activity, where the 12-hydroxypodocarpa-8,11,13-triene (7) showed GI 50 at 11.3 µM against melanoma SK-MEL5 (LC 50 = 48.3 µM and log 10 GI 50 = -4.95). The 12-acetyloxypodocarpa-8,11,13-triene (8) showed GI 50 at 12.1 µM against leukemia RPMI-8226 (LC 50 = 76.1 µM and log 10 GI 50 = -4.92).i.