Jihoon Lee

The analytical characteristics of Lyngbya wollei toxin 4 (LWTX4), a rare derivative of saxitoxin (STX), remain insufficiently documented due to its limited availability. In the present study, therefore, LWTX4 was synthesized using the previously reported synthetic route developed by Looper to elucidate its fundamental chromatographic behavior. Additionally, three other paralytic shellfish toxin analogues, STX, decarbamoyl saxitoxin (dcSTX), and 12-epi-LWTX4, were prepared from a common intermediate. Analysis of synthetic LWTX4 using the AOAC OMA 2011.02 HPLC–PCOX–FLD method yielded a retention time of 19.8 min, which overlapped with that of STX, and revealed that its FLD response was one-fourteenth that of STX. Meanwhile, under the AOAC 2021 HILIC–MS/MS conditions, LWTX4 eluted at 7.29 min, producing major product ions at m/z 205.1204, 182.0926, 164.0822, and 110.0720. These chromatographic and mass spectrometric characteristics provide useful reference data for assessing the possible presence of LWTX4 during PST profiling of biological samples. The synthetic STX and dcSTX exhibited chromatographic behavior consistent with that of their corresponding certified reference materials (CRMs) under the standard HPLC–PCOX conditions, supporting the potential use of synthesis as a complementary approach to the isolation of PSTs from dinoflagellates for the preparation of CRMs.

Luffariellolide (1) was previously isolated in useful quantities (>200 mg) from the marine sponge Suberea sp., collected from the Philippines. The intrinsic antibacterial activity of 1 was insignificant; however, 2-(pyridinyl)­pyridazinone 2, derived from 1, exhibited considerable activity against . In this study, 12 natural-product-like pyridazinones 3–14 were synthesized by modifying the γ-hydroxylbutyrolactone core of 1. Among them, 2-(5-fluoropyrimidinyl)­pyridazinone 11 was 64-fold more potent than 1 against , with a MIC of 2 μg/mL. Using a convergent five-step synthesis, the diterpene side chain of 11 was simplified to a C₁₂ lipid chain and 2-methyl-2-pentene to obtain 20 and 22, respectively, both of which retained the same MIC value as 11. The N-phenylnaphthalen-1-amine (NPN) uptake assays of 20 and 22 revealed their effective permeability to the outer membrane of , comparable to that of the positive control, polymyxin B. This study provides a foundation for future structural optimization of the novel antibacterial 2-(pyrimidin-2-yl)-5-alkyl-pyridazin-3­(2H)-one scaffold targeting .

Chemical investigation of n-hexane extract from the marine sponge Leucetta sp. led to the isolation of five new lipids, 1-5, each characterized by a substituted dioxolane core. The structures of 1-5 were established based on the interpretation of NMR and HRESIMS data. To assign the absolute configuration at C-1 ', model systems consisting of diastereomers at C-2, C-4, and C-1 ' of the dioxolane core were prepared from a chiral glycerol dimethylacetal. H-1 NMR inspection of model compounds revealed that a pair of C-1 ' epimers, 11a/c and 11b/d, was indistinguishable, restricting structural assignment by direct comparison of NMR data. In addition, the lack of chromophores in the dioxolane core resulted in unreliable ECD results, with Cotton effects appearing below 190 nm. As an alternative, a chiral NMR method using Eu(hfc)(3) revealed notable lanthanide-induced shifts, allowing the spectroscopic discrimination of 11a/c and ent- 11a/c. Therefore, the absolute configuration of all five new lipids was determined to be 2S, 4S, 1 ' S by direct comparison with the Eu(hfc)(3)-induced H-1 NMR data.

A chemical investigation of a methanol extract of Spongia sp., a marine sponge collected from the Philippines, identified 12 unreported scalarane-type alkaloids—scalimides A–L (1–12)—together with two previously described scalarin derivatives. The elucidation of the structure of the scalaranes based on the interpretation of their NMR and HRMS data revealed that 1–12 featured a β-alanine-substituted E-ring but differed from each other through variations in their oxidation states and substitutions occurring at C16, C24, and C25. Evaluation of the antimicrobial activity of 1–12 against several Gram-positive and Gram-negative bacteria showed that 10 and 11 were active against Micrococcus luteus and Bacillus subtilis, respectively, with MIC values ranging from 4 to 16 μg/mL.

The chemical investigation of the marine sponge Dysidea sp., which was collected from Bohol province in the Philippines, resulted in the identification of 15 new scalarane-type sesterterpenoids (1–1 4, 1 6), together with 15 known compounds. The chemical structures of the new compounds were elucidated based on NMR spectroscopy and HRMS. The structure of 12-epi-phyllactone D/E (15) isolated during this study was originally identified in 2007. However, careful inspection of our experimental ¹³C NMR spectrum revealed considerable discrepancies with the reported data at C-9, C-12, C-14, and C-23, leading to the correction of the reported compound to the C-12 epimer of 15, phyllactone D/E. The biological properties of compounds 1–16 were evaluated using the MDA-MB-231 cancer cell line. Compound 7, which bears a pentenone E-ring, exhibits significant cytotoxicity with a GI₅₀ value of 4.21 μM.

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.

Three new phenazine derivatives (1–3), along with known compounds (4–7) of saphenic acid derivatives, were isolated from a deep-sea sediment-derived yeast-like fungus Cystobasidium larynigs collected from the Indian Ocean. The structures of the new compounds (1–3) were determined by analysis of spectroscopic data, semi-synthesis and comparison of optical rotation values. All the isolated compounds (1–7), except for 2, showed nitric oxide (NO) production inhibitory effect against lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells without cytotoxicity at concentrations up to 30 μg/mL. This is the first report on the yeast-like fungus Cystobasidium laryngis producing phenazines and anti-inflammatory activity of 1–7 including saphenic acid (4).

Three furan-containing scalarane sesterterpenoids (1–3) and a novel pyrrole-containing analog (4) were isolated from the sponge Scalarispongia species. Compound 3, reported in the literature as a synthetic derivative of furoscalarol 2, was for the first time isolated from a natural source. During the separation performed using a silica column in the presence of methanol, 16-methoxy derivatives (5, 6) were obtained from the unintended reaction of 2. The isolated natural products 3 and 4 and the artifact 5 showed moderate to high cytotoxicity against six human cancer cell lines, whereas compound 6, the C-16 epimer of 5, showed no cytotoxicity at a concentration of 60 μΜ.

Three new sulfated steroidal glycosides (3–5), along with known cholesterol derivatives (1,2), were isolated from the visceral extract of the cone snail Conus pulicarius. The structure of each new compound was elucidated by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. The three new compounds exhibited significant in vitro cytotoxicity (GI₅₀ values down to 0.49 μM) against the K562 human leukemia cell line.