Chemical investigations of South American plants: Applications to drug discovery, biodiversity conservation and economic development

Abstract

This dissertation describes chemical investigations involving 11 Argentinean plant species and a sample of Chilean propolis. In total, 18 known and four novel compounds were isolated and identified. The compounds were tested in various antimicrobial assays. Three novel triterpenes, 3,4- seco-olean-12-en-3,28-dioic acid (4), 3alpha,-hydroxyolean-11-en-28,13 beta-olide (5), and 3alpha-hydroxyolean-11:13(18)-dien-28-oic acid ( 6) were isolated from the aerial parts of the Argentinean shrub, Junellia tridens (Lag.) Mold. (Verbenaceae). Another five compounds, oleanolic acid (1), oleanonic acid (2) and epioleanolic acid (3), all biosynthetically related to the three new oleananes, as well as epibetulinic acid (7) and sitosterol (8), were also isolated. LC-MS data are provided on the occurrence of these triterpenes in six other species of Junellia. We report the minimum inhibitory concentrations (MICs) of compounds 1--8 against Mycobacterium tuberculosis, and conclude that they are responsible for the antitubercular activity originally observed in the crude plant extract. Four other plants showing preliminary antitubercular activity were also investigated. The EtOAc extracts of Acantholippia seriphioides and Adesmia ameghinoi contained oleanolic acid (1) as their main constituent. The organic soluble portions of Chiliotrichium diffusum and Lathyrus magellanicus contained large amounts of ursolic acid (12) and sitosterol (8), respectively. Bioassay of the predominant compounds in these plants indicated that triterpenes were responsible for the antitubercular activity observed in the crude extracts. Fractionation of propolis (a product of honey beehives) from Colliguay in Central Chile led to the isolation, identification and bioassay of a novel gamma-lactone (14), five flavonoids (15--19), two diarylheptanoids (20--21), and a prenylated coumarin (22). All structures were elucidated primarily by 1D and 2D NMR and mass spectrometry. Based on the traditional use of propolis as an antimicrobial agent, the bioactivity of the purified compounds was determined against Staphylococcus aureus, Escherichia coli, Enterococcus faecium, and Candida albicans . Microscopic analysis of pollen present in the propolis provided clues to its botanical origins.