Marine dinoflagellates produce remarkable organic molecules, particularly those with polyoxygenated long‐carbon‐chain backbones, namely super‐carbon‐chain compounds (SCCCs), characterized by the presence of numerous stereogenic carbon centers on acyclic polyol carbon chains. Even today, it is a challenge to determine the absolute configurations of these compounds. In this work, the planar structures and absolute configurations of two highly flexible SCCCs, featuring either a C69‐ or C71‐linear carbon backbone, gibbosols A and B, respectively, each containing thirty‐seven stereogenic carbon centers, were unambiguously established by a combined chemical, spectroscopic, and computational approach. The discovery of gibbosols A and B with two hydrophilic acyclic polyol chains represents an unprecedented class of SCCCs. A reasonable convergent strategy for the biosynthesis of these SCCCs was proposed.

Comprehensive SummaryFifteen new meroterpenoids, littoreanoids A—O (1—15), including three rearranged skeleton meroterpenoids (1—3), were isolated from the mangrove‐derived fungus Penicillium sp. HLLG‐122. Compound 1 was a novel berkeleyacetal‐derived meroterpenoid featuring an unusual spirocyclic 2‐oxaspiro[5.5]undeca‐4,7‐dien‐3‐one moiety. Compound 2 possessed an unusual 6/6/6/6/6 pentacyclic system with a novel 1‐hydroxy‐7,7‐dimethyl‐2‐oxabicyclo[2.2.2]octan‐5‐yl acetate moiety. Compound 3 was an unusual 6/7/6/5/6/5/4 polycyclic systems containing a β‐lactone ring. The structures and absolute configurations of new compounds were elucidated by HRESIMS, NMR spectroscopy, single crystal X‐ray diffraction analysis, and electronic circular dichroism calculations. The plausible biosynthetic pathways of 1—3 were also proposed. Compounds 6 and 11 exhibited anti‐inflammatory effects with IC50 values of 30.41 and 19.02 μmol/L, respectively. The bioactive compound 11 was selected for the investigation of preliminary mechanism using molecular docking and Western blotting experiments. Compound 11 could suppress the levels of TNF‐α and IL‐6, and down‐regulate the protein expression of iNOS and COX‐2 in RAW 264.7 cells.

Angiogenesis and vasculogenic mimicry (VM) are crucial for the growth and metastasis of non-small-cell lung cancer (NSCLC). Most tumor angiogenesis inhibitors mainly target endothelial cell-mediated angiogenesis, ignoring tumor-cell-mediated VM and frequently leading to tumor recurrence and metastasis. Thus, development of bioactive molecules interfering with both tumor angiogenesis and VM is necessary. Identifying novel angiogenesis inhibitors from natural products is a promising strategy. Scoparasin B, a pimarane diterpene extracted from a marine-derived fungus, Eutypella sp. F0219, has an antibacterial effect. However, its effect on angiogenesis and VM remains unexplored. In this study, we first certified that scoparasin B showed a strong inhibition effect on angiogenesis and the VM process in vitro and ex vivo. Moreover, scoparasin B prominently impeded tumor growth, angiogenesis, and VM in an NCI-H1299 xenograft model. Further study revealed that scoparasin B restrained tumor angiogenesis and VM by reducing the VEGF-A level and suppressing the VEGF-A/ VEGFR2 signaling pathway. This study first demonstrated scoparasin B inhibited tumor angiogenesis, VM, and tumor growth of NSCLC and revealed its underlying mechanism. These new findings further support the potential of scoparasin B as a novel angiogenesis inhibitor and give a hint for further exploring potential angiogenesis inhibitors from natural products.