~ Pergamon PII: S0031-9422(97)00021-6 Phytochemisto,. Vol. 45, No. 4, pp. 801 805. 1997 ~3 1997 Published by Elsevier Science Ltd All rights reserved. Printed in Great Britain 0031 9422/97 $17.00 ~-0.00 TRITERPENES AND SESQUITERPENE LACTONES FROM CYCLOLEPIS GENISTOIDES CAROLA S. DE HELUANI, MARGARITA V. DE BOGGIATO,CESARA. N. CATAL,~N,JESf;S G. DiAZ,* THOMAS E. GI~DRIS*and WERNER HERZ* Instituto de Quimica Org~inica, Facultad de Bioquimica, Quimica y Farmacia, Universidad Nacional de Tucumfin, Ayacucho 471, 4000 S. M. de Tucumfin, Argentina; * Department of Chemistry, The Florida State University, Tallahassee, FL 32306-3006, U.S.A. (Received9 October 1996) Key Word Index--Cyclolepis gen&toides; Gochnatiinae; Mutisieae; Compositae; lupanes; ole- ananes; 12,13-epoxyoleanolic acid; 3fl,28-dihydroxylup-20(29)-en-30-al; triterpenes; guai- anolides; sesquiterpene lactones. Abstract--Aerial parts of Cyclolepis 9enistoides afforded a number of oleananes and ursanes including the new 12~,13~-epoxyoleanolic acid, lupanes including 3fl,30-dihydroxylup-20(29)-ene and the new 28-dihydroxylup- 20(29)-en-30-al and the sesquiterpene lactones deacylcynaropicrin, dihydroeleganin and isolippidiol. ©1997 Published by Elsevier Science Ltd. All rights reserved INTRODUCTION Cyclolepis yenistoides Don, the sole representative of a monotypic genus within Mutisieae, subtribe Goch- natiinae, occurs in salty soils ranging from southern Bolivia and Paraguay to southern Argentina [1]. Infusions of the aerial parts of this species, locally called 'palo azul' or 'matorro negro', are used in tra- ditional medicine for the treatment of renal disease. The only reference to previous chemical work is a statement that unlike most species belonging to genera within other subtribes of Mutisiae some genera of the Gochnatiinae, including Cyclolepis, gave only tri- terpenes [2]. We have now examined a collection of this species from near Tucum~n. RESULTSAND DISCUSSION In addition to oleanolic and ursolic acid, the main constituents of the extract, we isolated fl-amyrin, dihy- dro-fl-amyrin, oleanonic acid, taraxasterol, betulin, betulinic acid, methyl betulinate, the lupane la pre- viously reported from Flourensia heterolepis [3] and a Gyrnnosperma species [4], the new lupane lb and the new 12,13-epoxyoleanolic acid 2. The extract also furnished a complex mixture of sesquiterpene lactones. In an attempt to separate these, part of the mixture was acetylated and subjected to HPLC. This afforded the previously known 4b [5], kandavanolide (4e) [6], 8~-acetoxyzaluzanin C (4d) [7] and the new derivatives 5b, 5c, 6h and 6c, while the unacetylated portion furnished deacylcynaropicrin (4a) [8], ll,13fl-dihydrodeacylcynaropicrin (5a) [9] and isolippidiol (6a) [ 10]. Structures of the new deriva- tives are based on the ~H NMR spectra (Table i). The mono- and diacetates are presumably derived from the parent compounds 4a, 5a and 6a originally present in the extract. The structure of lb was clear from the mass spec- trum and the ~H NMR spectrum, which exhibited the usual signals of H-3 under an equatorial OH (dd at 6 3.17, J's = 12.5 Hz), an aldehydic proton at 6 9.51 conjugated with two methylene protons (singlets at 6 6.28 and 5.93), a hydroxymethylene (mutually coupled doublets at 6 3.80 and 3.37) and five methyl singlets whose shifts indicated that the primary hydroxyl was located on C-28. The structure of 2 could also be deduced from the mass spectrum which indicated the molecular formula C30H480 4 and the IH NMR spec- trum which established the presence of axial H-3 under an OH (ddat c53.25, J's = ! 1.5 and 4.5 Hz), an epoxidic proton at 6 3.03 (W~/2 approx. 6 Hz) and seven methyl singlets whose chemical shifts indicated that the carboxyl group was attached to C-17. The chemical shift and half-height width of the epoxidic proton was typical of a 12c~,13e- or 12fl,13fl-epoxy- oleanane [11 13]. While the two isomeric series can apparently be distinguished by t3C NMR spec- trometry [12], the available amount of the new epoxide was not sufficient to permit distinction by this method. An attempt to settle the matter by perbenzoic oxi- dation of oleanolic acid resulted only in formation of 3a, analogous to the action of various oxidizing agents, including perbenzoic acid on the acetate of 801