(−)-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.

Plants from the genus Salvia are used in traditional medicine worldwide and are considered a source of biologically active compounds due to the isolation of a diverse array of molecular skeletons, including terpenoids and polyphenols. Salvia melissodora is endemic to Mexico, occurring across the states of Aguascalientes, Durango, Guanajuato, Jalisco, Michoacán, Oaxaca, Puebla, and Querétaro, and is included in several ethnopharmacopeas from Mexico, highlighting its medicinal potential for treating respiratory and digestive affections, among others. The literature reports the presence of highly oxidized neoclerodane diterpenoids in S. melissodora as non-volatile metabolites, whereas caryophyllene, muurolene, spathulenol, caryophyllene oxide, and germacrene are described as the main constituents of the essential oil from the aerial parts. Given these antecedents, increasing knowledge about the chemical constituents of this useful plant becomes pertinent. In the present work, the phytochemical study of the aerial parts of S. melissodora was conducted by preparative chromatography to isolate oleanolic acid, 3β-acetoxyoleanolic acid, lupeol, 3β,20,25-trihydroxylupane, 3β,20-dihydroxylupane, kerlinic acid, spathulenol, and 5,3′-dihydroxy-6,7,4′-trimethoxyflavone. All compounds were characterized by their physical and spectroscopic data. Based on the herein-isolated metabolites and the literature on their biological potential, a partial association between the ethnopharmacological use of S. melissodora in Mexico and its chemical constituents could be suggested, thereby complementing previously reported accounts of this plant.