Halogenated Cyclic Monoterpenoids with Anti-Biofouling Activity from the Okinawan Red Marine Algae Portieria Hornemannii.

The red algal genus Portieria is a prolific producer of halogenated monoterpenoids. In this study, we isolated and characterised monoterpenoids from the Okinawan red algae Portieria hornemannii. A new polyhalogenated cyclic monoterpenoid, 2(R)-chloro-1,6(S)-dibromo-3(8)(Z)-ochtoden-4(R)-ol (1), along with three known monoterpenoids, (2R,3(8)E,4S,6R)-6-bromo-2-chloro-1,4-oxido-3(8)-ochtodene (2), 1-bromo-2-chloroochtoda-3(8),5-dien-4-one (3), and 2-chloro-1-hydroxyochtoda-3(8),5-dien-4-one (4) were isolated from the methanol extract of three populations of P. hornemannii. These compounds were characterised using a combination of spectroscopic methods and chemical synthesis, and the absolute stereochemistry of compounds 1 and 2 was determined. In addition, all isolated compounds were screened for their anti-biofouling activity against the mussel Mytilus galloprovincialis, and 1 exhibited strong activity. Therefore, halogenated monoterpenoids have the potential to be used as natural anti-biofouling drugs.

Structure-activity relationship of anti-inflammatory meroterpenoids isolated from Dictyopteris polypodioides in RAW264 cells.

In this study, we explored anti-inflammatory compounds from the brown alga Dictyopteris polypodioides and isolated 7 meroterpenoids. Their anti-inflammatory activities were evaluated using the lipopolysaccharide-stimulated mouse macrophage cell line, RAW264. Yahazunol (1) exhibited similar nitric oxide (NO) production inhibitory activity as zonarol (2), which has previously been shown to be an anti-inflammatory compound. Yahazunol (1), zonarol (2), and isozonarol (3) inhibited not only NO production but also inducible nitric oxide synthase, interleukin-6, and C-C motif chemokine ligand 2 mRNA expression in RAW264 cells. The structure-activity relationships of the 11 compounds, including their synthetic analogs, revealed the significance of the hydroquinone moiety in the anti-inflammatory activity of these sesquiterpenoids in RAW264 cells. Diacetylated zonarol (9) exhibited an activity comparable to that of zonarol as a result of intracellular deacetylation. These results provide new insights into the anti-inflammatory activity of hydroquinone-containing natural products.

Establishment of "Ring-Size-Divergent" Synthetic Strategy: Divergent Synthesis, Stereochemical Assignments, and Biological Activity Studies of Nerolidol-Type Sesquiterpenoids and Feroniellins.

Biomimetic epoxide-opening cascade cyclizations of polyepoxides enable the efficient and rapid construction of polyether skeletons. In this study, we discovered a method for switching the cyclization mode from tetrahydrofuran to tetrahydropyran (THP) formation in epoxide-opening cascades of polyepoxides. The THP formation proceeded via an epoxonium-ion intermediate by simple heating in neutral water. Next, by expanding the switching reaction, we successfully established a "ring-size-divergent" synthetic strategy that enabled the synthesis of the five-, six-, and seven-membered ether rings from identical diepoxide cyclization precursors under simple acidic or neutral conditions. The "ring-size-divergent" synthetic strategy was applied to the short divergent synthesis of nerolidol-type sesquiterpenoids and feroniellins, resulting in the revision of the proposed stereochemistry of certain natural products and the determination of all of the absolute configurations. Additionally, the anti-inflammatory activities of the synthetic samples were evaluated.

Two New Eremophilane-Type Sesquiterpenoids from Japanese Liverwort Bazzania japonica.

Two new eremophilane-type sesquiterpenoids, fusumaols A (1) and B (2), were isolated from the stem-leafy liverwort, Bazzania japonica collected in Mori-Machi, Shizuoka, Japan. Their structures were established using extensive spectroscopic (IR, MS, and 2D NMR) data, and the absolute configuration of 1 was determined by the modified Mosher's method. This is the first time eremophilanes have been discovered in the liverwort genus Bazzania. Compounds 1 and 2 were evaluated for their repellent activity against the adult population of the rice weevil Sitophilus zeamais using the modified filter paper impregnation method. Both sesquiterpenoids showed moderate repellent activities.

Asymmetric Total Synthesis of Toxicodenane A by Samarium-Iodide-Induced Barbier-Type Cyclization and Its Cell-Protective Effect against Lipotoxicity.

The asymmetric total synthesis of toxicodenane A, a sesquiterpenoid expected to be promising for diabetic nephropathy, was achieved. In the synthesis, a samarium iodide (SmI2)-induced Barbier-type cyclization and a regio- and stereoselective allylic oxidation followed by a dehydration cyclization were employed as key steps. Furthermore, the first asymmetric syntheses of both enantiomers were accomplished using the previously mentioned synthetic strategy. Finally, the synthetic compounds significantly inhibited lipotoxicity-mediated inflammatory and fibrotic responses in mouse renal proximal tubular cells.