Free Solvent Amidation of Ursolic and Oleanolic Acids of Fagraea Fragrans Fruits: Their P-388 Antitumor Activity

Abstract

This is an our laboratory effort in developing major compounds, ursolic acid (UA) and its isomer oleanolic acid (OA) of Fagraea Fragrans Roxb fruits, namely buah tembesu, Loganiaceae by free solvent amidation of the acids with n-buthylamine and phenylamine. The reactions have been conducted by using thionyl chloride as a chlorination reagent to make their acid chlorides respectively. In this reaction, the secondary hydroxyl group at C-3 position was preferably converted to be olefinic while the carboxyl group at C-28 position was normally amidated to give N-buthyl-urs-2,12-dien-28-amide [N-buthyl-olean-2,12-dien-28-amide] with yield 45.5% % and N-phenyl-urs-2,12-dien-28-amide [N-phenyl-olean-2,12-dien-28-amide] with yield 39%. Cytotoxic activity of amidation products toward P-388 murine leukemia cells was decreasing about half fold compared to starting material ursolic acid [oleanolic acid]. The IC50 values of N-butyl-urs-2,12-dien-28-amide [N-butyl-olean-2,12-dien-28-amide] and N-phenyl-urs-2,12-dien-28-amide [N-phenyl-olean-2,12-dien-28-amide] were 81, 4 μg/mL and 83.6 μg/mL respectively, whereas the IC50 value of ursolic acid [oleanolic acid] was 53.4 µg/mL.