A Cytotoxic Heterodimeric Cyclic Diarylheptanoid with a Rearranged Benzene Ring from the Seagrass Zostera marina

Abstract

The widespread seagrass Zostera marina contains a new diarylheptanoid heterodimer, zosterabisphenone C (1), featuring an unprecedented rearrangement of one of its benzene rings to a cyclopentenecarbonyl unit. The planar structure and absolute configuration of zosterabisphenone C were elucidated by a combination of spectroscopic (MS, ECD, and low-temperature NMR) and computational (DFT-NMR and DFT-ECD) evidence. Consistent with the previously isolated zosterabisphenones, compound 1 was selectively cytotoxic against HCT 116 adenocarcinoma colon cancer cells, reducing their viability by 73% at 10 μM (IC 50 of 7.6 ± 1.1 μM). The biosynthetic origin of zosterabisphenone C (1) from an oxidative rearrangement of zosterabisphenone A (4) is proposed.

Marine natural products

“…A new member of the zosterabisphenone family of diarylheptanoid dimers, zosterabisphenone C 1511 was reported from Northern Germany collections of the seagrass Zostera marina . 625 The structure contains an unusual spiro-fused γ-lactone moiety, proposed to be biosynthetically derived by rearrangement of co-metabolite zosterabisphenone A. Weak cytotoxicity towards the HCT-116 cell line was observed.…”

Spatial and Temporal Resolution of Cyanobacterial Bloom Chemistry Reveals an Open-Ocean Trichodesmium thiebautii as a Talented Producer of Specialized Metabolites

“…Determination of the relative configuration at C-2 and C-4 in 1 with respect to the C-14/C-17 segment was achieved using quantum-mechanical computational chemistry, namely, DFT prediction of 1 H and 13 C NMR chemical shifts (DFT-NMR). 32 Considering the structural complexity of compound 1, the truncated model compound 1m was used for the calculations, in which the flexible side chain of the natural compound is replaced by an isopropyl group. This strongly reduced the number of lowenergy conformations of the molecule, while it did not significantly affect the chemical shifts of the region of the molecule under study.…”

Spatial and Temporal Resolution of Cyanobacterial Bloom Chemistry Reveals an Open-OceanTrichodesmium thiebautiias a Talented Producer of Specialized Metabolites

“…Determination of the relative configuration at C-2 and C-4 in 1 with respect to the C-14/C-17 segment was achieved using quantum-mechanical computational chemistry, namely DFT prediction of 1 H and 13 C NMR chemical shifts (DFT-NMR). [36] Considering the structural complexity of compound 1, the truncated model compound 1m was used for the calculations, in which the flexible side chain of the natural compound is replaced by an isopropyl group. This strongly reduced the number of low-energy conformations of the molecule, while it did not significantly affect the chemical shifts of the region of the molecule under study.…”