Objective: Determine the structure, absolute configuration, and antiproliferative activity of a new furan diterpenoid isolated from the leaves of Coulteria velutina (Britton & Rose) Sotuyo & G.P.Lewis (Fabaceae). Methods: The structures of the natural product and those of 2 derivatives were established mainly by nuclear magnetic resonance spectroscopy, while their absolute configurations were established using vibrational circular dichroism involving comparison of the experimental and calculated spectra of a rigid derivative. Results: Isolation of (−)-(4 R,5 R,6 R,8 S,9 S,10 R,14 R)-6-[( E)- p-coumaroyloxy]vouacapan-18-oic acid (1), an undescribed secondary metabolite from the leaves of C velutina, is reported hereafter. Hydrolysis of 1 provided (+)-(4 R,5 R,6 R,8 S,9 S,10 R,14 R)-6-hydroxyvouacapan-18-oic acid (2), identical to a diterpenoid isolated from Caesalpinia echinata, but whose absolute configuration remained undetermined. Subsequent lactonization of 2 yielded (+)-(4 R,5 R,6 R,8 S,9 S,10 R,14 R)-vouacapan-6,18-olide (3). The absolute configurations of compounds 1–3 were established by vibrational circular dichroism studies of 3. In addition, the antiproliferative activity of the natural product 1 against HeLa, MDA-MB-231, Caco-2, and NIH/3T3 cell lines is reported. Conclusions: The leaves of C velutina yielded the new vouacapane 1. It showed weak antiproliferative activity against HeLa and MDA-MB-231 cancer cell lines (IC₅₀= 92.2 and 106.2 μg/mL, respectively), but was also weakly active against the NIH/3T3 healthy cell line (IC₅₀ value of 127.6 µg/mL). Its absolute configuration was determined by vibrational circular dichroism analysis of the conformationally rigid compound 3. This derivative can be used as a reference for the absolute configuration of related vouacapanes. In addition, this is the first phytochemical investigation of C velutina.

(−)-Patagonic acid (1) is a clerodane diterpene isolated from several plants from the Alismataceae, Asteraceae, Euphorbiaceae, Fabaceae, Lamiaceae, Salicaceae, Sapindaceae, and Velloziaceae families, and its biological potential as an inhibitor of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) and as an anti-inflammatory compound has been described. Furthermore, the enantiomer (+)-1 is also described in Fabaceae and Verbenaceae. A lack of formal studies about the absolute configuration (AC) determination of 1 is emphasized. Thus, the present manuscript describes the AC determination of patagonic acid (1). The chemical correlation of (−)-1 from (−)-hardwickiic acid (2) was achieved by a simplistic oxidative process. The specific rotation value and electronic circular dichroism (ECD) analysis allowed for the AC determination of (−)-1 as (5R,8R,9S,10R)-(−)-patagonic acid. ECD revealed a positive exciton chirality (EC) phenomenon in both (−)-1 and (−)-2, which is directly associated with their configuration and conformational preferences, which were assessed by DFT calculations at the B3LYP/DGDZVP level of theory. Since the NMR data of (+)-1 are fully coincident with those from its enantiomer studied herein, the chirality of (5S,8S,9R,10S)-(+)-patagonic acid could also be determined. These experimental conclusions deeply complement the literature related to clerodane compounds biosynthesized in several families of plants of scientific interest.

Strategic scaffolds in molecules increase the possibility of obtaining derivatives with potential uses in scientific and industrial areas. The regio- and stereoselective reactions can be considered to gain these tactical motifs. Natural diterpenes are key molecules for reaching such aims. Among this class of compounds, neo-clerodanes are highlighted by the presence of a furan moiety in their chemical structure. This work describes a regio- and stereoselective strategy to gain beta-lactone and oxirane derivatives from kerlinic acid (1) when the β,γ-unsaturated carboxylic acid system is oxidized, preserving the furan moiety. Oxidation of 1 yielded salviaolide (2), suggesting regio- and stereoselective means. A reaction mechanism was proposed when oxidation of the acetate (1a), benzoate (1b), and methyl ester (1c) derivatives from 1 were gained. The obtention of the epoxide derivative 3, kernolide (4), and kernolide epoxide (5) also supported the reaction mechanism. X-ray diffraction analysis of 3, Karplus-type analyses, and DFT calculations from hypothetical intermediates revealed conformational preferences that guide the regioselectivity. The stereoselectivity was attributed to the natural origin of 1. All compounds were characterized by their physical and spectroscopical data. These results suggest the feasibility of promoting regioselective oxidation on neo-clerodane compounds, preserving the furan moiety.

Nuclear Magnetic Resonance (NMR) is a powerful technique for elucidating the structure of organic molecules, and it is especially useful in determining the structure of natural products, including terpenes. 3-Oxo-γ-costic acid is an eudesmene-type sesquiterpene that has been isolated from different vegetable species of the Asteraceae and Lauraceae families. Its ¹H NMR has been reported with some discrepancies in the chemical shift assignments as well as in J values. In the present work, 3-oxo-γ-costic acid was isolated from the dichloromethane extract of the aerial parts of Ageratina glabrata by chromatographic means and the complete assignment of the ¹H NMR spectrum of 3-oxo-γ-costic acid is reported using a hybrid protocol that involves a DFT-calculated spectrum and the experimental ¹H spectrum. The calculated spectrum was constructed based on the DFT-calculated J values for each hydrogen, and the respective chemical shifts are those recorded by experimental means, which are supported by 2D NMR. Then, the completely calculated ¹H spectrum was simulated in the Mnova software and compared with the experimental spectrum. This methodology is especially useful for the detection of low magnitude NMR couplings (<2 Hz), which are complicated to measure experimentally; then, this hybrid protocol, experimental-DFT, could be applied to NMR determination of more complex sesquiterpenes.

Plants from the Randia genus (Rubiaceae) are used in Mexican traditional medicine, where diseases such as diabetes, cancer, and chronic inflammation are treated with these plants. Particularly, Randia echinocarpa Sessé & Moc. ex DC (endemic in Mexico) is used in the northern region to treat kidney diseases and stomach disorders, while in the central area, this plant is used to treat circulatory and lung diseases, cancer, diabetes, and malaria. Previous research on this plant has highlighted the antibacterial potential of extracts from leaves and stems and nematicidal and antioxidant activities for fruit extracts. Phytochemical studies of this plant have been poorly explored, though the presence of mannitol, triterpene, and phytosterol compounds as main components in extracts from fruits was described. In this research, the chemical study of leaves and fruits of R. echinocarpa is described. The presence of gardenoside as the main component of the methanolic extract from leaves was determined after a phytochemical analysis. This compound could be directly related to the use of R. echinocarpa in traditional medicine since scientific reports suggested its potential as an anti-inflammatory and a pain suppressor, as well as its inhibitory effect on free fatty acid (FFA)-induced cellular steatosis. In addition, β-gardiol was isolated from fruit extract. A chemical correlation of β-gardiol with gardenoside was performed by enzymatic hydrolysis. Other components, including ursolic acid, stigmasterol, sitosterol, and D-mannitol, were also identified. All compounds were characterized by their physical and spectroscopic data.