Sophia Khom

Procerones are highly brominated marine natural products that were isolated in 2019 from Polycarpa procera. Herein, we report the first total syntheses of procerones A and B, together with their enantiomers, in only three linear steps, starting from commercially available acetophenone and benzaldehyde derivatives. The synthesis takes advantage of a chalcone core structure obtained by Aldol condensation followed by Davis oxidation to implement the chiral α-hydroxy ketone moiety without the use of heavy metals. The effects of all synthesized compounds, including the enantiopure natural products, on the major inhibitory neurotransmitter receptor in the mammalian brain (GABAA receptor) were determined, and the four enantiopure procerones were additionally tested for antiprion activity. While no antiprion activity was observed for the tested compounds, one unprecedented precursor, as well as procerone B and its enantiomer, significantly enhanced GABAA receptor function, suggesting that this scaffold may serve as a starting point for developing novel GABAA receptor modulators.

Rubrolides are marine natural products with numerous biological activities. Over the last few decades, more than 20 members of this natural product class have been isolated, but their mode of action remains unknown. All compounds share a furanone core structure with β‐aryl and γ‐benzylidene substituents. The highly brominated rubrolides T, U, and an analog of rubrolide U are synthesized for the first time. Furthermore, the developed method enables the synthesis of natural rubrolides A, D, and P as pure Z ‐isomers. The synthetic approach employs a Suzuki‐Miyaura cross‐coupling reaction with a dibrominated aromatic boronic species as the key step, followed by a vinylogous Aldol condensation to introduce the second aromatic substituent. The synthesized compounds are biologically tested and show outstanding antibiofilm activity for Stenotrophomonas maltophilia , Bacillus subtilis , and Staphylococcus aureus. All synthesized compounds shows only negligible effects at GABA _A receptors, suggesting that they are unlikely to exert neurotoxic effects at a concentration of 10 µM.

This study aimed to investigate the glycaemic control potential and modulation of GABA-induced chloride currents (I_GABA) of H. revolutum and the possible bioactive xanthones. Fractions from the leaf and stem extracts (dichloromethane and methanol) were assessed for in vitro α-glucosidase-inhibitory potential and their ability to modulate I_GABA (GABAergic effect) through GABA_A receptors heterologously expressed in Xenopus oocytes. Xanthones 4-hydroxy-2,3-dimethoxy-9H-xanthen-9-one (1), 3-hydroxy-2,4-dimethoxy-9H-xanthen-9-one (2) and trans-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-5-methoxy-2,3-dihydro-7H-[1,4]dioxino[2,3-c]xanthen-7-one (3) were isolated from the stem and tested in the GABA_A receptors assay, but only 3 was assessed for α-glucosidase-inhibitory action. Compared to acarbose (IC₅₀ = 6.16 µM), 3 showed a mild to moderate α-glucosidase-inhibitory activity (IC₅₀ = 45.1 µM), which may be attributed to the absence of a hydroxyl group at its xanthone core. Isomeric compounds 1 and 2 significantly enhanced I_GABA with similar efficacy, while 3 was inactive, which may be attributed to its notable structural difference (cyclic ether substitution) compared to compounds 1 and 2. H. revolutum stem contains xanthones with α-glucosidase-inhibitory potential, which also enhance I_GABA and could be further studied as a medicinal plant for managing GABA_A receptor-mediated mental disorders and/or diabetes.

From both pharmaceutical and structural perspectives, the large family of prostaglandins represent a truly remarkable class of natural products. Prostaglandin A₂ is a tissue hormone naturally found in human seminal plasma and in the sea whip Plexaura homomalla with yet poorly understood biological or therapeutic effects. Herein, a novel strategy for the stereoselective construction of both naturally occurring prostaglandin A₂ epimers and first insights into their functional effects on the major inhibitory neurotransmitter γ‐aminobutyric acid (GABA) type A receptors (GABA_AR) are provided. The synthesis of both epimers was achieved in only 11 steps starting from commercially available 2,5‐dimethoxy‐tetrahydrofuran employing an organocatalytic domino‐aldol reaction, a Mizoroki‐Heck reaction, a Wittig reaction as well as an oxidation‐decarboxylation sequence. The (15R)‐epimer significantly reduced GABA‐induced currents through GABA_A receptors while its (15S)‐epimer did not show any significant effect. These data suggest that (15R)‐PGA₂ might serve as a novel scaffold for the development of selective GABA_A receptor modulators.