neo-Clerodane Diterpenes from Salvia herbacea Elihú Bautista, Emma Maldonado, and Alfredo Ortega* Instituto de Química, Universidad Nacional Autó noma de Mé xico, Circuito Exterior, Ciudad Universitaria, Coyoaca ́ n 04510, D. F., Me ́ xico * S Supporting Information ABSTRACT: Chemical investigation of the aerial parts of Salvia herbacea led to the isolation of eight new neo-clerodane diterpenes (1-8), named tehuanins A-H, and three known compounds. The structures of these compounds were determined by analysis of their spectroscopic data. Three of the new diterpenes possess a 1,8-epoxy group (1-3). This unusual structural feature was confirmed by X-ray diffraction of 1. The structure of the previously isolated 1α,10α- epoxysalviarin was revised. The absolute configuration of 6 was established by X-ray diffraction analysis of its bromo derivative 6a. Cytotoxic and anti-inflammatory activities of these diterpenes were examined. None of the compounds were considered to be cytotoxic; however, compound 7 exhibited anti- inflammatory activity comparable to that of indomethacin. Salvia is one of 224 genera in the family Lamiaceae. This subcosmopolitan genus comprises about 900 species, including some that are used for ornamental, culinary, or medicinal purposes. 1 Salvia species have been utilized in traditional Mexican medicine to treat dysentery, diarrhea, and insomnia and for their abortive, expectorant, and antipyretic properties. 2 Metabolites reported from this genus include triterpenes, 3 flavonoids, 4 sesterterpenes, 5 and diterpenes. Diterpenes from Salvia are mainly abietanes and neo-clerodanes, many of them with modified skeletons. 6 Some of these diterpenes have shown cytotoxic, 7 antiprotozoal, 8 and phytotoxic activities, 9 and one of them, salvinorin A, is a nonalkaloidal, naturally occurring hallucinogen and also the first non-nitrogenous κ-opioid selective agonist. 10 Salvinorin A was isolated from Salvia divinorum, 11 a hallucinogenic plant used by Mazatec healers in magical rites of divination. As a part of our ongoing study of diterpenes from Salvia, we have now investigated the aerial parts of Salvia herbacea Benth. (Lamiaceae, subgenus Calosphace), a herbaceous plant that grows on the Isthmus of Tehuantepec in Southern Mexico. Herein, we report the structural elucidation of the isolates from this plant and the results of tests of their cytotoxic and anti-inflammatory activities. ■ RESULTS AND DISCUSSION Fractionation of a Me 2 CO extract of aerial parts of S. herbacea led to the isolation of eight new diterpenes, tehuanins A-H (1-8), together with the known 1(10)-dehydrosalviarin (9), 12 1α,10α-epoxysalviarin (10), previously isolated from Salvia lineata, 13 and 5,6,3′-trihydroxy-7,4′-dimethoxyflavone. 14 The published structure of compound 10 will be discussed. Tehuanin A (1) was isolated as colorless crystals. It has the molecular formula C 20 H 20 O 6 , as deduced from the [M + H] + ion at m/z 357.1330 in the HRFABMS. Its 13 C NMR spectrum showed 20 signals, and the IR spectrum indicated the presence of γ- and δ-lactones and a furan ring. This information together with previous studies of the chemistry of genus Salvia subgenus Calosphace 6a suggested that 1 had a neo-clerodane skeleton. The 1 H and 13 C NMR spectra of 1 (Table 1) showed the presence of a tertiary methyl group (δ H 1.30 s, δ C 23.6, CH 3 -20), a furan ring (δ H 6.45, H-14; δ H 7.44, H-15; δ H 7.51, H-16), a 18,19-γ- lactone (δ C 172.8, C-18; δ C 76.3, δ H 4.68, 4.10, CH 2 -19), and a Received: February 23, 2012 Published: May 11, 2012 Article pubs.acs.org/jnp © 2012 American Chemical Society and American Society of Pharmacognosy 951 dx.doi.org/10.1021/np3001464 | J. Nat. Prod. 2012, 75, 951-958