Antimycobacterial Cycloartanes from Borrichia frutescens

In a bioassay-guided search for antimycobacterial compounds from higher plants of the southeastern United States, we have chemically investigated the sea daisy (Borrichia frutescens) from coastal marshes of Louisiana for their active constituents. Bioactive chromatographic fractions provided two new triterpenes, (24R)-24,25-epoxycycloartan-3-one (<BO>1</BO>) and (23R)-3-oxolanosta-8,24-dien-23-ol (<BO>4</BO>), and (3αH,24R)-24,25-epoxycycloartan-3-ol (<BO>3a</BO>). Compound <BO>3a</BO> had been previously isolated as a mixture of C-24 epimers. The structures of <BO>1</BO>, <BO>3a</BO>, and <BO>4</BO> were established by spectroscopic methods and chemical transformations, and the molecular structures of <BO>1</BO> and <BO>4</BO> were determined by single-crystal X-ray diffraction. In a radiorespirometric bioassay against Mycobacterium tuberculosis, the epoxycycloartanes <BO>1</BO> and <BO>3a </BO>exhibited minimum inhibitory concentrations of 8 μg/mL. In contrast, the lanostadiene-type triterpene <BO>4</BO> showed no significant inhibition at 128 μg/mL, as did the acetate <BO>3b</BO>. Cytotoxicity for Vero cells gave IC<INF>50</INF> values of 71.8, 39.8, and 103.6 μg/mL for triterpenes <BO>1</BO>, <BO>3a</BO>, and <BO>4</BO>, respectively.