Jong Seok Lee

Marine macroalgae are drawing growing interest as underutilized feedstocks for chemicals and fuels and as high-productivity, carbon-assimilating biomass that could contribute to carbon capture and sequestration strategies. Here, we investigate an ionic-liquid-assisted hydrothermal conversion of Gracilaria verrucosa (Rhodophyta; red alga) to formic acid (FA) and levulinic acid (LA) using 1-methyl-3-(4-sulfobutyl)imidazolium hydrogen sulfate ([SBMim][HSO4]). Under optimized conditions (210 °C, 5 h), FA and LA were produced in 18% (3.0 g/L) and 38% (6.36 g/L) yields, respectively. In a 10 g scale experiment, FA was recovered as an aqueous solution in 4% isolated yield via vacuum distillation, while LA was obtained as a solid in 29% isolated yield via ethyl acetate extraction. The ionic liquid was reconditioned using an activated carbon–Celite–S108H protocol and reused over ten consecutive cycles while maintaining FA/LA yields. Preliminary PMI/E-factor and break-even analyses further clarified the sustainability advantages and lab-scale economic limitations of the process. Importantly, the recovered FA was evaluated as a substrate for biohydrogen production using the hyperthermophilic archaeon Thermococcus onnurineus NA1, which couples formate oxidation to growth. Macroalgae-derived FA supported a hydrogen production rate comparable to that obtained with chemical-grade FA in batch culture. Overall, this work demonstrates a recyclable, ionic-liquid-assisted hydrothermal platform for converting marine macroalgae into value-added organic acids, integrating product recovery with downstream biohydrogen generation and underscoring the potential of macroalgal biorefineries for sustainable chemicals and energy.

δ‐Lactones are structurally diverse natural products broadly distributed across plants, fungi, microbes, and marine organisms. Their six‐membered cyclic ester scaffold, often embedded in polyketide, terpenoid, fatty acid‐derived, or hybrid frameworks, underpins wide‐ranging pharmacological activities, including cytotoxic, antimicrobial, antiparasitic, and anti‐inflammatory effects as well as modulation of enzymes and signaling pathways. Clinically relevant examples such as lovastatin, the first FDA‐approved statin, and artemisinin, a cornerstone antimalarial, highlight the therapeutic value of δ‐lactone motifs. In contrast, fostriecin and leptomycin B, though unsuccessful in the clinic, inspired analog development and validated new biological targets. Recent advances in synthesis—including ring‐closing metathesis, CH lactonization, asymmetric annulations, and biomimetic approaches—have streamlined access to complex δ‐lactones, enabling stereocontrolled synthesis and structure–activity relationship studies. This review provides a comprehensive overview of bioactive natural δ‐lactones, organized by biosynthetic origin, and emphasizes their structural diversity, biological functions, and synthetic accessibility.

We report the design and synthesis of thieno[3,2-b]pyridin-5(4H)-one derivatives exhibiting site-dependent modulation of both antitumor activity and fluorescence, enabled by a regioselective BOP-promoted aza-[3 + 3] cycloaddition. The reaction proceeds between thiophen-3-amines and α,β-unsaturated carboxylic acids, followed by base-induced dehydrogenation. Mechanistic studies reveal that the head-to-tail aza-[3 + 3] annulation involves a C-1,4 conjugate addition, leading to an intramolecular amide coupling. Evaluation of the photophysical properties and antitumor activities demonstrated that the biological and optical behaviours of the thieno[3,2-b]pyridin-5(4H)-one scaffold are dependent on the aryl substitution site. Specifically, 3-aryl derivatives exhibited notable antitumor activity, whereas 2-aryl analogues displayed strong fluorescence, highlighting the potential of this scaffold for dual-function applications. DFT calculations supported the observed divergence in fluorescence by revealing differences in orbital conjugation and HOMO–LUMO gaps. In addition, selected compounds showed low cytotoxicity toward MRC-9 cells, indicating favourable cancer cell selectivity.

Herein, we report the first- and second-generation syntheses of (+)-ieodomycins A and B and their stereoisomers via the late-stage elaboration of their conjugated E-diene side chains. Key steps for successful synthesis included Keck asymmetric allylation to introduce a hydroxyl group at the C5 position, consecutive Wipf’s carboalumination modification, iodination, Sharpless asymmetric dihydroxylation, one-carbon homologation via cyanation, Mukaiyama lactonization, and Stille cross-coupling to form the conjugated E-diene moiety. Further, the preliminary in vitro bioactivity profile against various disease-related molecular targets and cell lines was investigated. Results indicated that compounds 30b and 30c, diastereoisomers of (+)-ieodomycin B (2), serve as α-glucosidase inhibitors, while compounds 30b and 30d inhibit the angiotensin-converting enzyme.

Herein, we describe a gold(I)-catalyzed intermolecular formal [2 + 2 + 2] cycloaddition of a carbonyl compound and a propiolate. A series of highly substituted 2H-pyrans are accessed regioselectively from acyclic and cyclic ketones and aldehydes with various substituted propiolates using Ph₃PAuCl (0.1-1 mol %) with two distinct metal triflate additives [0.75-7.5 mol %; In(OTf)₃/Cu(OTf)₂ for ketones, Bi(OTf)₃/Hf(OTf)₄ for aldehydes]. This method should provide an opportunity for further development of synthetic access to other heterocyclic compounds.

Fluorescent probes are attractive tools for biology, drug discovery, disease diagnosis, and environmental analysis. In bioimaging, these easy-to-operate and inexpensive probes can be used to detect biological substances, obtain detailed cell images, track in vivo biochemical reactions, and monitor disease biomarkers without damaging biological samples. Over the last few decades, natural products have attracted extensive research interest owing to their great potential as recognition units for state-of-the-art fluorescent probes. This review describes representative natural-product-based fluorescent probes and recent discoveries, with a particular focus on fluorescent bioimaging and biochemical studies.

Herein, we describe an original synthetic method for a series of fluorescent thieno[3,2-b]pyridine-5(4H)-one derivatives prepared via the gold(I)-catalyzed 6-endo-dig intramolecular hydrothiophenylation process involving N-thiophen-3-yl alkynylamides. The brightness was improved; emission could be tuned, and larger Stokes shifts were recorded. We also designed and synthesized the phalloidin-based fluorescent chemical probes KF-P1 and KF-P2 to realize fluorescent F-actin imaging.

A fluorescent probe (4-(2-(4-(diethylamino)phenyl)-4-methyl-5-oxo-4,5-dihydrothieno[3,2-b]pyridin-7-yl)phenyl 2,4-dinitrobenzenesulfonate, KF-DNBS) for facile detection of H₂S in serum was developed based on the combination of an environment-sensitive fluorophore (2-(4-(diethylamino)phenyl)-7-(4-hydroxyphenyl)-4-methylthieno[3,2-b]pyridin-5(4H)-one, KF) with albumin and the 2,4-dinitrobenzene sulfonyl (DNBS) group as a recognition unit for H₂S. KF-DNBS showed remarkable fluorescence enhancement due to H₂S-triggered thiolysis followed by the formation of a fluorescent fluorophore (KF)-albumin complex. The H₂S detection limit of KF-DNBS was estimated to be 3.2 μM, and KF-DNBS achieves a high selectivity to H₂S over biothiols by employing 2-formyl benzene boronic acid (2-FBBA) as an effective masking reagent. Furthermore, under optimized sensing conditions, KF-DNBS could be applied to accurately determine spiked H₂S in human serum without the need for any further procedure for the removal of serum proteins.

A total of eight new oxygenated 4-exo-methylene sterols, 1–8, together with one artifact 9 and six known sterols 11–16, were isolated from the marine sponge Theonella swinhoei collected from the Bohol province in Philippines. Structures of sterols 1–8 were determined from 1D and 2D NMR data. Among the sterols, 8α-hydroxytheonellasterol (4) spontaneously underwent an allylic 1,3-hydroxyl shift to produce 15α-hydroxytheonellasterol (9) as an artifact; this was rationalized by quantum mechanical calculations of the transition state. In addition, the 1,2-epoxy alcohol subunit of 8α-hydroxy-14,15-β-epoxytheonellasterol (5) was assigned using the Gauge-Independent Atomic Orbital (GIAO) NMR chemical shift calculations and subsequent DP4+ analysis. Finally, comparison of the ¹³C chemical shifts of isolated 7α-hydroxytheonellasterol (6) with the reported values revealed significant discrepancies at C-6, C-7, C-8, and C-14, leading to reassignment of the C-7 stereochemistry in the known structure.