A Bis-benzopyrroloisoquinoline Alkaloid Incorporating a Cyclobutane Core and a Chlorophenanthroindolizidine Alkaloid with Cytotoxic Activity from <i>Ficus fistulosa</i> var. <i>tengerensis</i>

Tengerensine (<b>1</b>), isolated as a racemate and constituted from a pair of bis-benzopyrroloisoquinoline enantiomers, and tengechlorenine (<b>2</b>), purified as a scalemic mixture and constituted from a pair of chlorinated phenanthroindolizidine enantiomers, were isolated from the leaves of <i>Ficus fistulosa</i> var. <i>tengerensis</i>, along with three other known alkaloids. The structures of <b>1</b> and <b>2</b> were determined by spectroscopic data interpretation and X-ray diffraction analysis. The enantiomers of <b>1</b> were separated by chiral-phase HPLC, and the absolute configurations of (+)-<b>1</b> and (−)-<b>1</b> were established via experimental and calculated ECD data. Compound <b>1</b> is notable in being a rare unsymmetrical cyclobutane adduct and is the first example of a dimeric benzopyrroloisoquinoline alkaloid, while compound <b>2</b> represents the first naturally occurring halogenated phenanthroindolizidine alkaloid. Compound (+)-<b>1</b> displayed a selective in vitro cytotoxic effect against MDA-MB-468 cells (IC₅₀ 7.4 μM), while compound <b>2</b> showed pronounced in vitro cytotoxic activity against all three breast cancer cell lines tested (MDA-MB-468, MDA-MB-231, and MCF7; IC₅₀ values of 0.038–0.91 μM).