Pergamon S0031-9422(96)00108-2 Phytochemistry, Vol. 42, No. 5, pp. 1369-1373, 1996 Copyright © 1996 Elsevier Science Ltd Printed in Great Britain. All rights reserved 0031-9422196 $15.00 + 0.00 SESQUITERPENE LACTONES FROM STEVIA VAGA LuIs R. HERN.g.NDEZ, Cl~SAR A. N. CATALSd~, CARLOS M. CERDA-GARCfA-ROIAS* and PEDRO JOSEPH-NATHAN*t Instituto de Qufmica Org~aica, Facultad de Bioqufmica, Qufmica y Farmacia, UniversidadNacional de Tucumfin, Ayacucho 491, S.M. de Tucumfin 4000, Argentina; *Departamentode Qufmica, Centlo de Investigaci6ny de Estudios Avanzados, Instituto Polit6cnicoNacional, Apartado 14-740, M6xico, D.F. 07000, M6xico (Received 8 December 1995) Key Word Index--Stevia vaga; Eupatorieae; Compositae; sesquiterpene lactones; guaianolides; germacranolides; heliangolides; melampolides; flavonoids. Abstract--The aerial parts of Stevia vaga afforded four new gualanolides, four new germacranolides, one new melampolide and three new heliangolides as well as two known flavones. The structures were established mainly by NMR spectroscopy. INTRODUCTION In continuation of our work on the chemical con- stituents of Argentinean Stevia species [1-5] we report herein the isolation and structure elucidation of twelve new substances from a collection of Stevia vaga Griseb. whose distribution is limited to La Rioja and Catamarca provinces in northwestern Argentina [6]. The aerial parts of this plant yielded melampolide la, germac- radienolides 2-5 gualanolides 6-9, heliangolides I0- 12 and the known flavones eupatilin [7] and casticin [81. RESULTSAND DISCUSSION The structure of melampolide la was readily as- signed when its IH NMR spectrum (Table 1) was compared with the data reported for its positional isomer lb, previously isolated from S. amambayensis [9], S. aristata [10] and S. breviaristata [4]. An AB system centered at ~4.83 and a quartet at 8 7.13 coupled to a methyl doublet at t~ 1.97 indicated the replacement of the 4-acetyloxytiglate in lb by a 5- acetyloxytiglate in la. Its 13C NMR spectrum (Table 2) as well as its EIMS data (see Experimental) were also in agreement with the proposed structure. Although compounds 2 and 12 were isolated as a mixture in a 1.3 : 1 ratio, respectively, the IH NMR data for each compound could be obtained from the spec- trum by a careful analysis of the integrals as well as by extensive decoupling experiments. The ~H NMR data of 2 (Table 1) closely resembled those of 3B-acetoxy- 8fl-(4'-hydroxytigloyloxy)-14-hydroxycostunolide, a tAuthor to whom correspondence should be addressed. compound previously isolated from Stevia breviaristata [4], excepting the signals for the ester group at C-8 which is now a 5-hydroxytiglate (sarracenate) residue. The structure of lactone 12 was assigned from its ~H NMR data since they were in close agreement with those of heliangolides bearing 3a,8fl-oxygen functions [ll]. The most diagnostic data were the signal of H-7, which appears as a broadened signlet at t~ 2.98, the signal of H-3 which appears at 8 4.60 as a double doublet with J2~.3 = 5 and JEb.3 = 11 Hz, and the small coupling constant values JTA3a (2.5 Hz), JT.13b (2.0 HZ) and J6.7 (2.0 Hz). Since compounds 10 and 11 are closely related to 12, their structures were easily deduced from their ~H NMR spectra. The main differences were found in the coupling constants of H-3 (J2a.3 = J2b.3 = 3 Hz in 10 and 11 vs. J2a.3 = 5 and J2b,3 = 11 Hz in 12) indicating the change in the C-3 stereochemistry. On the other hand, heliangolide 10 corresponded to the 14-hydroxy derivative of a previously reported substance, 3fl-hy- droxy-8fl-tigloyloxyheliangolide [12], which gave us additional comparative 1H NMR data to support the structure of 10. The structures of 3-5 were determined from their 1H NMR data and from comparison with related analogs [4, 10] which differ only in the nature of the ester side chain at C-8. In the same way, the structure of gualanolide 7 and the corresponding C-10 epimer 9 could be deduced by comparison with the NMR data of breviarolide [13] and lO-epi-breviarolide [4]. Location of the acetate group in both 6 and 8 was evident from the downfield shift of the CH2-5' signals of the sarracenate ester residue. Finally, the ~H NMR data of guaianolides 6-9 revealed that, as in the case of lO-epi-breviarolide with respect to breviarolide, the stereochemical change at 1369