Biologically Active Natural Products from Mongolian Medicinal Plants Scorzonera diWaricata and Scorzonera pseudodiWaricata Nanzad Tsevegsuren, ‡,² RuAngelie Edrada, ‡ Wenhan Lin, ⊥ Rainer Ebel, ‡,| Claudia Torre, ‡ Sofia Ortlepp, ‡ Victor Wray, § and Peter Proksch* ,‡ Institut fu ¨r Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-UniVersita ¨t Du ¨sseldorf, UniVersita ¨tsstrasse 1, Geb. 26.23, 40225 Du ¨sseldorf, Germany, Department of Organic and Food Chemistry, Faculty of Chemistry, National UniVersity of Mongolia, Ulaanbaatar, Mongolia, State Key Laboratory of Natural and Biomimetic Drugs, Peking UniVersity, Beijing, People’s Republic of China, and Department of Structural Biology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany ReceiVed January 9, 2007 Chromatographic separation of a crude extract obtained from the aerial parts of the Mongolian medicinal plant Scorzonera diVaricata yielded the two new quinic acid derivatives feruloylpodospermic acids A and B. Both compounds feature a feruloyl group and two dihydrocaffeoyl substituents. For feruloylpodospermic acid A, the dihydrocaffeic acid substituents were found esterified at positions 1 and 5 of the quinic acid moiety, while the feruloyl group was attached at position 3. For feruloylpodospermic acid B, the substituents were linked at positions 1, 3, and 4. The aerial parts of S. pseudodiVaricata that are likewise used in Mongolian traditional medicine yielded two further new natural products, for which the names scorzoneric acid and scorzonerin are proposed. Scorzoneric acid is an unusual phenolic compound featuring a central tetrasubstituted phenyl ring to which a glucose unit is bound, which in turn is substituted by an esterified acyl side chain. Further substituents of the central phenyl ring system include a butan-2-one group, which is linked to a second para-substituted phenyl ring system. Scorzonerin is a matricarin-based sesquiterpene lactone that carries an esterified dihydrocoumaric acid moiety, which in turn is glycosidically bound to glucose. The structures of all new compounds were unambiguously established from NMR ( 1 H, 13 C, COSY, HMBC) spectroscopic and mass spectrometric data. The new quinic acid derivatives feruloylpodospermic acids A and B exhibited strong antioxidative activity when analyzed in the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay. About 170 species of the genus Scorzonera (family Asteraceae) are distributed around the world. 1,2 Chemically, the genus, like many other members of the tribe Lactuceae, is characterized by the accumulation of terpenoids, consisting mainly of polyisoprenes, triterpenes, and diterpenoid resins deposited in parenchymatic cells of roots and stems in amounts up to 20-30% of the dry matter. 3 Some species of the genus have been widely utilized as food and medicinal supplements. S. hispanica, known as vipers grass, is used as a nutritional condiment to stimulate appetite and as an herbal medicine, especially against pulmonary diseases, as well as colds. Furthermore, it was described to be a stomachic, diuretic, and antipyretic. Its roots are edible and may be used as a coffee substitute. Another species, S. humilis, known as humble vipers grass, was even exploited to adulterate Arnica, while its young leaves are consumed as vegetables. Of industrial importance are S. kirghisorum and S. tau-saghyz, which are considered as valuable sources of natural rubber. 1 Eleven species of Scorzonera are found in Mongolia, one of which is endemic, while five are subendemic. 4 Two of the latter, S. diVaricata and S. pseudodiVaricata, are used in folk medicine in Mongolia. Both species are widely distributed in Middle Khalkha, East Mongolia, Depression of Great Lakes, Valley of Lakes, East Gobi, Govi Altai, Transaltai Gobi, and Alashan Gobi. They grow on thin sandy desert steppes, rubble slopes, and terrains of mountains and knolls, or at the bottom of dry riverbeds. S. diVaricata Turcz is a perennial herbaceous plant reaching 15-30 cm in height. Its root and herbs are reported to have antipyretic and antidote activity and are used in traditional medicine for treatment of poisonous ulcers as well as malignant stomach neoplasia. 5 S. pseudodiVaricata Lipsch is also a perennial herba- ceous rosette plant, 50 cm in height with yellow flower heads. It is also widely used in Mongolian traditional medicine for the treatment of diarrhea, parasitic diseases, lung edema, and fever caused by bacterial and viral infections, as well as for its diuretic properties. 6 No phytochemical studies have been recorded for S. diVaricata and S. pseudodiVaricata. For the genus Scorzonera, previous chemical investigations have been carried out on S. austriaca, S. hispanica, S. humilis, S. tomentosae, S. cretica, and S. columnae, resulting in the isolation of sesquiterpenes, 7-10 lignans, 11,12 neolig- nans, 13 phenolic acids, triterpene derivatives, 9,14 stilbene deriva- tives, 15 dihydroisocoumarins, 16 and flavonoids. 17 In this paper, we report the isolation, structure elucidation, and biological activity of four new natural products from the aerial parts of S. diVaricata and S. pseudodiVaricata. Results and Discussion Analysis of the EtOAc extract of a MeOH extract of the respective aerial parts of S. diVaricata and S. pseudodiVaricata, using HPLC-DAD and LC-MS, indicated the presence of several unknown natural products in addition to known compounds such as scopoletin, simple quinic acid congeners, and flavonoid deriva- tives as shown in Table 1. Our interest was focused on the isolation of new biologically active compounds, which were monitored by a bioassay-guided isolation scheme in parallel with the analysis of the HPLC-DAD/MS chromatograms of the fractions. Further chromatography of the EtOAc extract of S. diVaricata yielded two new DPPH-active feruloylquinic acid derivatives, for which we propose the names feruloylpodospermic acids A (1) and B (2). From S. pseudodiVaricata, a novel phenolic compound and a new sesquiterpene lactone glycoside were isolated, for which we designated the trivial names scorzoneric acid (3) and scorzonerin (4), respectively. * To whom correspondence should be addressed. Tel: 0049/211- 8114163. Fax: 0049/211-8111923. E-mail: proksch@uni-duesseldorf.de. ‡ Institut fu ¨r Pharmazeutische Biologie und Biotechnologie. ² Permanent address: Department of Organic and Food Chemistry, Faculty of Chemistry, National University of Mongolia, Ulaanbaatar, Mongolia. ⊥ National Research Laboratory of Natural and Biomimetic Drugs. | New address: Department of Chemistry, University of Aberdeen, Meston Building, Meston Walk, Old Aberdeen, AB24 3UE Scotland, U.K. § Department of Structural Biology, Helmholtz Centre for Infection Research (HZI). 962 J. Nat. Prod. 2007, 70, 962-967 10.1021/np070013r CCC: $37.00 © 2007 American Chemical Society and American Society of Pharmacognosy Published on Web 06/02/2007