(−)-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.

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.