Sesquiterpene Lactones from Neurolaena oaxacana ⊥ Claus M. Passreiter,* ,† Jesus Sandoval-Ramirez, ‡ and Colin W. Wright § Institut fu ¨ r Pharmazeutische Biologie, Heinrich-Heine-Universita ¨ t Du ¨ sseldorf, Universita ¨ tsstrasse 1, D-40225 Du ¨ sseldorf, Germany, Facultad de Ciencias Quimicas, Benemerita Universidad Autonoma de Puebla, Puebla, Mexico, Postgraduate Studies in Pharmaceutical Technology, The School of Pharmacy, University of Bradford, West Yorkshire, BD7 1DP, U.K. Received February 3, 1999 Twelve sesquiterpene lactones, two new (1 and 2) and 10 known neurolenin-type germacranolides and furanoheliangolides (3-12) were isolated from Neurolaena oaxacana, and their structures were elucidated by NMR and GC-MS analysis. The chemotaxonomic importance of these findings is discussed. As N. lobata is used against dysenteries, neurolenin B (4) and a mixture of the neurolenins C (5) and D (6) were tested against Entamoeba histolytica and Giardia intestinalis. The genus Neurolaena (Asteraceae) occurs in tropical areas of southern Mexico, Guatemala, and other Central American states. 1 Except for the widely distributed N. lobata, which is frequently used in the traditional medicine of most countries in this region, 2,3 all other species are less popular due to their limited distribution. Nevertheless, some species are used in their particular area of distribu- tion as alternatives when N. lobata leaves are unavailable. 4 Taxonomic considerations have also made the genus Neurolaena interesting, and its placement within the Asteraceae was a subject of considerable discussion. 5-7 Relationships within the genus, as seen by the flavonoid chemistry of some species, are more complex than would be expected from their morphology. Turner has divided the genus Neurolaena into two sections, Brevipalea and Neu- rolaena, based on differences in length of the receptacular bracts of the species. 1 For these botanical reasons, N. macrocephala is more closely related to N. lobata, both members of the section Neurolaena, than it is to N. oaxacana of the section Brevipalea, although the lack of flavones and 6-hydroxykaempferol derivatives seems to differentiate N. macrocephala from the other two. 8,9 Recently, we reported the occurrence of sesquiterpene lactones in N. lobata, N. cobanensis, and N. macro- cephala, 4,10,11 and their biological activities. 12,13 Our find- ings could not support the chemical differences within the section Neurolaena between N. macrocephala and N. lobata as found for the flavonoids. 8,9 Although N. macrocephala is the only species in which ester derivatives built from isobutyric acid have been found, 4,10 it generally contains the same type of sesquiterpene lactones as N. lobata and N. cobanensis. In continuation of our studies on sesquit- erpene lactones, we now report the occurrence of sesquit- erpene lactones from N. oaxacana, a member placed together with N. cobanensis in the series Radiata of the section Brevipalea. 1 Additionally, we have tested the activities of the main sesquiterpene lactones against Entamoeba histolytica and Giardia intestinalis, both well known to cause gastrointes- tinal infections, as N. lobata is also used against dysentery in Guatemala and other Meso-American states. Results and Discussion The dichloromethane extract of N. oaxacana B.L. Turner (Asteraceae) leaves afforded two new neurolenins 1 and 2 in addition to the known neurolenin-type germacranolides neurolenins A (3), B (4), C (5), D (6), G (7), and H (8), lobatin A (9), lobatin B (10), and the two calyculatolides (11 and 12), previously isolated from N. lobata 10 and N. cobanensis, 4 respectively. Both new compounds (1 and 2) contained an isobutyryloxy substituent, which was obvious from an intense fragment ion at m/z 71 in the MS of each compound. Whereas the molecular ion (m/z 366) indicated 1 to be a neurolenin derivative containing only one ester moiety, it could be assumed that 2 (M + 408) was a diester derivative containing an additional acetyl group. Because the MS of 2 contained an intense fragment at m/z 250, only found for 9 at that intensity, compound 2 could be a derivative of 9, differing in the ester moiety at C-8. The structures of 1 and 2 were further elucidated from their NMR spectra. The 1 H NMR of 1 displayed signals for 24 protons. The signals of 17 protons, representing the * To whom correspondence should be addressed. Tel.: +49 211 8114172. Fax: +49 211 8111923. E-mail: passreit@uni-duesseldorf.de. † Heinrich-Heine-Universita ¨t Du ¨ sseldorf. ‡ Benemerita Universidad Autonoma de Puebla. § University of Bradford. ⊥ Dedicated to Prof. Dr. B. C. Lippold on the occasion of his 60th birthday. 1093 J. Nat. Prod. 1999, 62, 1093-1095 10.1021/np990038t CCC: $18.00 © 1999 American Chemical Society and American Society of Pharmacognosy Published on Web 07/14/1999