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 twodimensional NMR spectra. The relative configurations of these molecules were established via 1H-1H 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 mu M. Compounds 1 and 5 were also cytotoxic against human ovarian (OVCAR3) and melanoma (MDA-MB-435) cancer cell lines.

Automated summary

This article reports a relatively young class of fungal metabolites, macrocyclic alkaloids with a cyclopenta[b]fluorene ring system, which were first discovered in 2013. The structures of these compounds were identified by analyzing high-resolution electrospray ionization mass spectrometry data and one-dimensional and two-dimensional NMR spectra. The relative and absolute configurations of these alkaloids were determined through various spectroscopic techniques. These compounds showed cytotoxic activity against human cancer cell lines.