Embellicines C-E: Macrocyclic Alkaloids with a Cyclopenta[b]fluorene Ring System from the Fungus Sarocladium sp.

Macrocyclic alkaloids with a cyclopenta[b]fluorene ring system are a relatively young structural class of fungal metabolites, with the first members reported in 2013. Bioassay-guided fractionation of a Sarocladium sp. (fungal strain MSX6737) led to a series of both known and new members of this structural class ( 1 - 5 ), including the known embellicine A ( 1 ), three new embellicine analogues ( 2 , 4 , and 5 ), and a semisynthetic acetylated analogue ( 3 ). The structures were identified by examining both high-resolution electrospray ionization mass spectrometry data and one-dimensional and two-dimensional NMR spectra. The relative configurations of these molecules were established via 1 H- 1 H coupling constants and nuclear Overhauser effect spectroscopy, while comparisons of the experimental electronic circular dichroism (ECD) spectra with the time-dependent density functional theory ECD calculations were utilized to assign their absolute configurations, which were in good agreement with the literature. These alkaloids ( 1 - 5 ) showed cytotoxic activity against a human breast cancer cell line (MDA-MB-231) that ranged from 0.4 to 4.8 μM. Compounds 1 and 5 were also cytotoxic against human ovarian (OVCAR3) and melanoma (MDA-MB-435) cancer cell lines.