Meroterpenoids are a distinctive class of natural products found in various organisms, including animals, plants, bacteria, algae, and particularly fungi. Among them, spiromeroterpenoids, which have a spiro-ring connecting a terpenoid and a non-terpenoid moiety, are markedly unique. Currently, only a limited number of plants from the families Myrtaceae, Hypericaceae, Annonaceae, Asteraceae, and Lauraceae are known to biosynthesize spiromeroterpenoids. The non-terpene moiety of plant-derived spiromeroterpenoids is generally a polyketide, mainly a functionalized phloroglucinol derivative such as syncarpic acid and tasmanone. However, a flavanone, as found in the syzygioblanes isolated from Syzygium oblanceolatum (Myrtaceae), is another rare non-terpene component. The terpene moieties are restricted to monoterpenes or sesquiterpenes. The spiro-ring is generally formed by [m + n] cyclization or, in some cases, by radical or ionic cyclization.

Sulfur-containing compounds are found in various medicinal products, where they play crucial roles in biological activities such as antimicrobial, anticancer, and other therapeutic effects. These compounds are commonly found in species of Allium, especially onions and garlic; however, there is little evidence of their presence in other plants. In particular, sulfur-containing iridoid glycosides with anticancer properties, which are very promising compounds as pharmaceutical seeds, have been isolated from Paederia scandens (Rubiaceae), also known as the skunk vine because of its strong smell caused by methyl mercaptan. Herein, we describe the isolation and structural elucidation of 3 new iridoid glycosides from the aerial parts of P. scandens. Their biosynthetic pathways are also discussed.

The phytochemical investigation of the rainforest plant Croton argyratus (Euphorbiaceae) led to the isolation of two halimane-type diterpenes, crotargyolides A (1) and B (2), with an uncommon γ-lactone ring at C-5 and C-9, together with a crotofolane-type diterpene, 3-hydroxylated crotofolin C (3, crokocrotogenoid A), and the known clerodane diterpenes, junceic acid (4) and epoxyjunceic acid (5). The structures of the newly isolated compounds were elucidated by various NMR techniques, high resolution (HR)MS analysis, and electronic circular dichroism (ECD) spectroscopy. The proposed biosynthetic pathway of 1 from 4 was discussed. Crotargyolide A (1) and known compounds 4 and 5 were evaluated for antiproliferative activity and displayed no growth inhibitory effect toward all tested tumor cell lines.

Two new isoflavone glucosides, irisolone 4′-O-[O-β-d-glucopyranosyl-(1→6)-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside] (1) and iriskashmirianin 4′-O-[O-β-d-glucopyranosyl-(1→6)-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside] (2) were isolated from the underground parts of Iris florentina (Iridaceae). The structures of 1 and 2 were determined based on extensive spectroscopic data analyses and hydrolytic cleavage results. The isoflavone derivatives previously isolated from this plant were evaluated for their ability to inhibit the formation of advanced glycation end products.

Retinoid X receptors (RXRs) are nuclear receptors involved in various crucial biological processes, such as gene regulation, metabolism, and cell differentiation. They predominantly function as heterodimers with other nuclear receptors and modulate gene expression in response to ligand binding. Additionally, they act as therapeutic targets for different conditions, such as cancer and metabolic disorders. Although synthetic RXR agonists, such as bexarotene, are used in clinical settings, they exert adverse side effects. In this study, to explore insights into potential natural RXR agonists as alternatives to existing drugs, we isolated 14 coumarins, including 1 new compound from Boenninghausenia albiflora var. japonica (Rutaceae). Among them, daphnoretin methyl ether (14), a known biscoumarin, was found to exhibit subtype-nonspecific RXR agonist activity.

The Silene genus plants in the Caryophyllaceae family are a large genus with over 850 species. It has been known that Silene genus plants contain triterpenoid saponins. These saponins have glucuronic acid in the sugar chain and are difficult to separate in chromatography. In this study, a strategy was developed to clarify the distribution of triterpenoid saponins in whole plants of Silene vulgaris by isolation of neutralized saponins using methylation reactions, which were used as standard substances for LC-MS analysis, and elucidating their characteristic MS and MS/MS fragment patterns. The n-butanol fraction of the methanol extract from the whole plant of S. vulgaris was separated to obtain fractions including saponins by octadecyl silica column chromatography. Then, each fraction was treated with trimethylsilyl diazomethane for methylation of the carboxyl groups of glucuronic acid in the molecules, and five triterpenoid methylated saponins (7a, 13a, 14a, 16a, and 17a) were isolated using HPLC. The chemical structures of the isolated compounds were determined by spectroscopic analyses including NMR and MS, and their characteristic fragmentations were also clarified in LC-MS and MS/MS. It was performed on the n-butanol fraction from the whole plant of S. vulgaris, and the chemical structures of 22 triterpenoid saponins were estimated based on the MS and MS/MS fragmentation patterns of the isolated triterpenoid saponins.

Six flavonoids (1–6), including 3 previously undescribed compounds (1–3), were isolated from the dried roots and stem skins of Daphne giraldii Nitsche. The strategy of LC-tandem mass spectrometry-based Global Natural Products Social Molecular Networking (GNPS) molecular network technology and NMR-based Small Molecule Accurate Recognition Technology (SMART) technology facilitated the precise separation of isopentenyl flavonoids in D. giraldii. The structures were determined through comprehensive spectroscopic analysis. Furthermore, all compounds were evaluated for their cytotoxic activity against Hep3B cells. Specifically, compounds 1 and 3 exhibited significant cytotoxicity with IC₅₀ values of 5.52 ± 0.57 and 2.53 ± 0.49 μM, respectively, compared to the positive control sorafenib (IC₅₀ = 7.08 ± 0.23 μM).

This study established a ¹H-NMR-based biochemometric approach for the isolation of biologically active compounds from complex extracts. In both pharmacognosy and natural product chemistry, reliably isolating bioactive compounds typically necessitates repeating time-consuming and laborious isolation and purification steps, presenting a bottleneck in many studies. We applied biochemometric methods to accurately estimate active compounds, thus minimizing the number of assays and isolation steps. The rhizomes of Alpinia officinarum Hance (Zingiberaceae) have been continuously prescribed in traditional Japanese medicine as stomachics and analgesics, despite a limited understanding of the mechanisms underlying these effects. Additionally, transient receptor potential vanilloid subtype 1 (TRPV1) plays a role in modulating nociception, respiratory defense responses, and gastrointestinal protection. Accordingly, ¹H-NMR-based biochemometry was employed to search for TRPV1-active components in A. officinarum rhizome extracts by combining TRPV1 activity intensity with ¹H-NMR data. However, initially, the active component could not be identified because the principal component analysis loading plot primarily displayed only buckets of primary metabolites. Consequently, we applied orthogonal partial least squares to the ¹H-NMR spectra, which allowed us to identify specific spectral bins at 1.66 ppm (aliphatic) and 7.02, 6.98, 6.82, and 6.74–6.58 ppm (aromatic), correlating with TRPV1-stimulating activity. Based on this prediction, diarylheptanoids were swiftly identified, and their potential to activate TRPV1 was confirmed by administering the identified compounds to TRPV1-expressing cells. These findings highlight the potential of chemometric analysis using ¹H-NMR spectroscopy for identifying the chemical classes responsible for the bioactive properties of complex crude drug extracts.