Phymchmiw y. Vol. 26, No. 6. pp. 174 7-1750. 1987. 0031~ 9422/ 87 53.00 + 0.00 Pr int ed zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA in Great zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Britain. Q 1987 Pcr gamon Journals Ltd. zyxwvutsrqp SESQUITERPENE LACTONES FROM STEVZA OVATA AND CRYSTAL STRUCTURE OF 11,13-DEHYDROERIOLIN Josh S. CALDER~)N, LEOVIGILDO QUIJANO, FEDERICO G~MEZ-GARIRAY, DONATO M. zyxwvutsrqponmlkjihgfedcbaZYX SANCHEZ, TIRS~ RIOS and FRANK R. FRONCZEK. lnstituto de Quiinica, Univcrsidad Nacionol Autbnoma de Mixica, Ciradto Exterior,Ciudad Universitaria,Coyoach 04510. M&x&, D.F.; l Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, U.S.A. (Ret&d recciued 11 Nooember 1986) Key Word Index--Slevia ouatq Compositaq Eupatoricac; germacrolidc; guaianolide; sesquiterpcne lactones; crystal structure. Abstract-The aerial parts of Steuia ouata afforded three sesquiterpenc lactones, of which one was new. Its structure was established by spectroscopic methods and chemical reactions. One of the compounds, 4a,S&epoxy-8cpi-inunolide was chemically correlated with 11,13dehydroeriolin. The structure of the latter was confirmed by single crystal X-ray diffraction. The conformation of 11.13dehydroeriolin in the solid is chair-chair [ lsDs, ,D’* J. INTRODUCHON The genus Stevia (tribe Eupatorieae, subtribe Piqueriinae) [l] with about 15&200 species is abundant in Mexico [2]. So far phytochemical investigations have shown that this genus is chemically heterogeneous [3]. As part of our chemical systematic study of the tribe Eupatorieae, we have previously analysed Stevia monar- daefolia [4, S] and Steuia rhombifolia H.B.K. [6], which according to Grashoff [7] is synonymous with Stevia ouata Willd. Previous studies on this, species afforded the paniculosides I-V [8], a longipinene derivative [9] and two bisabolene derivatives [lo]. We now report the isolation and structure elucidation of the new sesquiter- pene lactone 4-acetyl-8cpLinuviscolide (1) and the known lactones 4a, S/Lepoxy-8-epi-inunolide (5) and inuviscolide (7) [ 111. RESULTS AND DISCUSSION 4-Acetyl-8-epi-inuviscolide (1) had the molecular for- mula C1,HZ204 and was shown to be a sesquiterpene lactone of the guaianolide type. IR absorptions at 1730 cm-’ indicate the presence of an acetate group (m/z 230 due to [M -601’) and at 1765 cm-’ which are typical of an a&unsaturated y-lactone. This is supported by the presence of two doublets typical of the lactonic exocyclic methylene at 66.27 (J = 2.2) and 5.66 (J = 2.0) in the ‘H NMR spectrum of 1. Also the ‘H NMR of 1 exhibited two broad singlets at 64.92 and 4.99 which were assigned to an exocyclic methylene group (IR absorption at 900 cm- ‘). The doublet of doublet of doublets at 64.53 (J = 10,7.5,5.0 Hz) was assigned to H-8, since irradiation of this signal affected H-9 and converted a broad signal at 63.07 into a broad triplet assigned lo H-7. Conversely, irradiation at 63.07 (H-7) affected H-8 and collapsed the conjugated exocyclic methylene proton signals lo singlets. The cis-lactone ring fusion was deduced from the allylic l Contribution No. 826 from Instituto de Quimica, U.N.A.M. coupling constants of the C-13 methylene according to Samek’s rule [12] and the chemical shift of H-8 (64.53) shifted to lower field compared with that of inuviscolide (64.33) (7) which possesses Wan.9 annelation [ 111. We have observed that in C-8 closed y-lactones, the H-8a (equatorial) signal in cis-y-lactones has a higher chemical shift that the H-8/3 (axial) signal in [runs-y-lactones, for instance tomentosin (64.67) [13] and its 8cpimer xan- thisonin (64.24) [13]; helenalin acetate (64.90) [14] and its l-epimer bigelovin (64.66) [ 151; ivangustin (64.86) [ 163 and B-epi-ivangustin (64.09) [ 111; pleniradin acetate (65.39) [ 173 and its lepimer gaillardin (64.48) [ 181. Therefore the chemical shift of H-8 seems to be suf- ficiently characteristic for assignment of the C-8 lactone ring closure. The acetoxy group in 1 was placed at C-4 in the following manner. Acid hydrolysis of 1 afforded an elimination product characterized as zinniolide (2) [19]. Selective epoxidation of 2 with mchloro perbenzoic acid produced the acpoxide 3. Its stereochemistry was de- duced on the reasonable assumption that the peracid attacked from the less hindered a-face. Treatment of epoxide 3 with boron trifluoride furnished the ketone 4 (“mu 1740 cm - ‘), thus establishing the acetoxy group at C-4 and the methylene group at C-10. Since the acetoxy group undergoes in high yield bimolecular elimination toward C-3 rather than toward C-5, as in pseudoivalin [20], the stereochemistry of the acetoxy group is very likely a[ZO]. The stereochemistry of H-l and H-5 zyxwvutsrqponmlk must be the same as in zinniolide (2). Based on all these facts we propose 1 as the more likely structure for 4-acetyl-8-epi- inuviscolide. The second compound isolated, 4a,5/3epoxy-8-epi- inunolide (S), C1 sH2r,03r mp 95-98”, exhibited IR and ‘HNMR features which closely resembled those of a substance isolated from lnula species [13], to which structure 8 has been assigned only with a different stereochemistry at C-4, C-5 and a c&fused lactone ring, in spite of the chemical shift of H-8, which was markedly different from that of inunolide [21], for which the stereochemistry of the lactone ring was established as cis. 114 1