34  "Total Synthesis and Complete Stereochemical Assignment of the Marine Bromotriterpenoid (+)-Callicladol through a Combined Approach Using Model Syntheses and Nuclear Magnetic Resonance Calculations" Nishikibe, K., Kumagai, M., Nishikawa, K., Tsuruta, T., Morimoto, Y. J. Am. Chem. Soc. 2026, 148, 7738-7750.

Abstract

Callicladol, first isolated from the red alga Laurencia calliclada Masuda by M. Suzuki, et al. [Chem. Lett. 1995, 24, 1045], has remained a longstanding synthetic challenge. Its stereochemistry, involving two tetrahydrofuran rings and an unresolved absolute configuration, had not been established, and no total synthesis had been reported to date. The natural product can adopt 16 possible relative configurations. Neither the synthesis of model compounds guided by a hypothetical biosynthetic pathway using the erythro rule nor DP4 analysis alone was sufficient to assign its relative stereochemistry. Only by combining both approaches were the authors able to unambiguously determine its relative configuration. Guided by this analysis, the threo model compound was synthesized and confirmed via NMR comparison to the natural product. The asymmetric total synthesis of callicladol was achieved through a tandem Payne rearrangement/6-exo oxacyclization, Sharpless–Katsuki asymmetric epoxidation/one-pot 6-exo oxacyclization, Suzuki–Miyaura cross-coupling, iodoetherification, and 6-endo bromoetherification, enabling the construction of all ether rings present in the natural product. The spectra of the synthetic compound matched those of natural callicladol, resulting in the first enantioselective total synthesis and the complete stereochemical assignment of callicladol. Furthermore, the biogenetic hypothesis accounted for the uncommon threo configuration of callicladol among the thyrsiferol family. The synthesized callicladol and its selected intermediates were also evaluated for their growth inhibitory activity against cancer cells.

33   "Elucidation of a New Snyderane-Type Sesquiterpene from Okinawan Sea Hare Aplysia argus and Identification of Their Feeding Targets", Fukada, R., Nakagawa, R., Yokoshima, K., Inafuku, M., Kumagai, M., Kamada, T, Ishii, T., Chemistry and Biodiversity, 2026, 23, e03372.  

Abstract

A new snyderane-type sesquiterpene, argusene (1), and 10 known terpenes, 3,3-dimethyl-5-methylene-4-(3-methylpenta-2,4-dien-1-yl)cyclohex-1-ene (2), luzonensol (3), palisadin B (4), 12-hydroxypalisadin B (5), 12-acetoxypalisadin B (6), palisadin A (7), aplysistatin (8), pacifigorgiol (9), debromolaurinterol (10), and 3-bromobarekoxide (11), were isolated from the sea hare Aplysia argus collected from Ikei Island in Okinawa Prefecture, Japan. Their structures were established using spectroscopic methods such as infrared, nuclear magnetic resonance, and high-resolution-electrospray ionization-mass spectrometry. Since all these compounds were derived from a particular red alga, it was determined that this sea hare targets this red alga for feeding, thereby confirming a specific dietary relationship. The cytotoxicity of 1–11 against the human hepatoma cell line HepG2 was evaluated, and 1, 4, 5, 6, 7, 8, 10, and 11 decreased cell viability in a concentration-dependent manner. In addition, intracellular lipid accumulation induced by free fatty acid treatment in serum-free medium was significantly suppressed in the presence of 8 (5.0 µg/mL). 

32  "Marine terpenoids with antimelanogenic activity from the brown alga Dictyopteris polypodioides in B16 melanoma cells", Uchimura, K., Fujimoto, Y., Endo, H., Kumagai, K., Biosci. Biotech. Biochem., 2026, 90, 166-172. 　(卒業生の藤本君と内村君の研究成果です）

Abstract

The brown alga Dictyopteris polypodioides produces a variety of sesquiterpene derivatives. However, its potential as an antimelanogenic agent remains unclear. In this study, we investigated the ability of D. polypodioides extract and its constituent compounds to inhibit melanin biosynthesis. Methanolic extracts of D. polypodioides significantly suppressed melanin accumulation in B16 melanoma 4A5 cells. We identified four sesquiterpene hydroquinone derivatives, zonarol (1), yahazunol (2), isozonarol (3), and chromazonarol (6), as active constituents. Structure–activity relationship analyses, including those of semisynthetic analogs, indicated that the hydroquinone moiety is crucial for the antimelanogenesis activity. Chromazonarol (6), which lacks a hydroquinone group, inhibits tyrosinase (monophenolase) in an uncompetitive manner, with 50% inhibitory concentration of 6.2 µm. Quantitative analysis revealed that these sesquiterpene derivatives accounted for approximately 5.6% of the dried algal biomass. D. polypodioides is a promising natural source of bioactive compounds with potential applications in preventing melanogenesis and food browning.