New Eremophilenolides from Cacalia pilgeriana

Abstract

Five new eremophilenolides and a known sesquiterpene were isolated from the methanol extract of the roots of Cacalia pilgeriana. Their structures were identified as 1β-hydroxy-2β-methyl-senecioyloxyeremophil-7(11)-en-8β(12)-olide (1), 1β-hydroxy-2β-methylsenecioyloxy-8α-methoxyeremophil-7(11)-en- 8β(12)-olide (2), 2β-hydroxy-3β-methylsenecioyloxyeremophil-7(11)-en-8α(12)-olide (3), 2β,8β-dihydroxy-3β-methylsenecioyloxyeremophil-7(11)-en-8α(12)-olide (4) and 1β,8β-dihydroxy-2β,3α-diangeloyloxyeremophil-7(11)-en-8α(12)-olide (5) and caryolane-1,9β-diol (6) by spectroscopic methods including 2D-NMR techniques (¹H-¹H COSY, HMQC, HMBC) and HR-ESI-MS. The structure and relative stereochemistry of compound 1 were unequivocally established by X-ray diffraction analysis. Bioassays showed compounds 3 and 5 to possess strong cytotoxic activity in vitro against human leukemia cells (HL-60) (IC₅₀ < 15 μg mL^-1). The structure-activity relationship is discussed.

Key words

Cacalia pilgeriana - Compositae - eremophilenolides - sesquiterpenes - cytotoxic activity

References

• 1 How K C. A Dictionary of the Families and Genera of Chinese Seed Plants. 2nd edn. Beijing; Science Press 1998: p 75
• 2 Chinese Crude Drugs C o. Zhongguo Zhongyao Ziyuan Zhiyao. Beijing; Science Press 1994: p 1271
• 3 Xue Z W, Yu Y Q. Index Flora of Chinese Medicinal Herbs. Beijing; People’s Health Press 1996: p 754
• 4 Correa J, Romo J. The constituents of Cacalia decomposita. A. Gray: structures of maturin, maturinin, maturone and maturinone. Tetrahedron 1966: 685-91
• 5 Joseph-Nathan P, Negreta M C, Gonzalez M P. Studies in Cacalia species.  Phytochemistry. 1970;  9 1623-8
• 6 Takemoto T, Kusano G, Aota K, Kaneshima M, Emary N A. Studies on the constituents of Cacalia spp. I. The constituents of Cacalia auriculata DC. var. kamtschatica (Maxim.) Matsumura. (1).  Yakugaku Zasshi. 1974;  94 1593-6
• 7 Naya K, Miyoshi Y, Mori H, Takai K, Nakanishi M. The sesquiterpenes of Cacalia species. Chem Lett 1976: 73-6
• 8 Casares A, Maldonado L A. The structure of cacalone. Tetrahedron Lett 1976: 2485-8
• 9 Naya K, Takai K, Nakanishi M, Omura K. The sesquiterpenes of Cacalia species II. The structure of cacalal and the interconversions of the constituents. Chem Lett 1977: 1179-82
• 10 Omura K, Nakanishi M, Takai K, Naya K. The sesquiterpenes of Cacalia species: 8-oxocacalol and the stereochemistry of cacalone epimers. Chem Lett 1978: 1257-60
• 11 El-Emary N A, Takemoto T, Kusano G. New sesquiterpenes from the roots of Cacalia auriculata .  Planta Med. 1980;  38 161-4
• 12 Kuroyanagi M, Naito H, Noro T, Ueno A, Fukushima S. Furanoeremophilane-type sesquiterpenes from Cacalia adenostyloides .  Chem Pharm Bull. 1985;  33 4792-7
• 13 Krasovskaya N P, Kulesh N I, Denisenko V A. Natural antioxidants furanoeremophilanes from Cacalia root.  Khim Prir Soedin. 1989;  5 643-5
• 14 Rodriguez-Hahn L, Guzman A, Romo J. Constituents of Cacalia decomposita. IV. Structure of decompostin. Tetrahedron 1968: 477-83
• 15 Samek Z, Harmatha J, Novotny L, Sorm F. Absolute configuration of adenostylone, neoadenostylone and isoadenostylone from Adenostyles alliariae (Gouan) Kern, and decompostin from Cacalia decomposita A. Gray.  Coll Czech Chem Commun. 1969;  34 2792-807
• 16 Hayashi K, Nakamura H, Mitsuhashi H. Sesequiterpenes from Cacalia hastate .  Phytochemistry. 1973;  12 2931-3
• 17 Zhang S M, Zhao G L, Li R, Lin G Q. Eremophilane sesquiterpenes from Cacalia roborowskii .  Phytochemistry. 1998;  48 519-24
• 18 Mao M J, Jia Z J. Eremophilane sesquiterpenes from Cacalia ainsliaeflora .  Planta Med. 2001;  67 1-5
• 19 Mao M J, Yang Z D, Jia Z J. New eremophilane sesquiterpenes from Cacalia ainsliaeflora .  Planta Med. 2003;  69 745-9
• 20 Wang Y, Yang M, Yuan C S, Han Y F, Jia Z J. Sesquiterpenes and other constituent from Cacalia deltophylla .  Pharmazie. 2003;  58 596-8
• 21 Wang P F, Yang C, Jia Z J. Studies on the chemical constituents of Cacalia pilgeriana .  J Lanzhou Univ (Natural Sciences). 2003;  39 61-3
• 22 Shao H J, Feng J T, Han J, Li G Z, Zhang X. Primary study on antifugal activity of 32 plant extracts.  J Northwest Sci Tech Univ Agric For. 2003;  31 59-62
• 23 Skehan P, Storeng R, Scudiero D. New colorimetric cytotoxicity assay for anticancer-drug screening.  J Natl Cancer Inst. 1990;  82 1107-12
• 24 Heymann H, Tezuka Y, Kikuchi T, Supriyatna S. Constituents of Sindora sumatrana Miq. I. Isolation and NMR spectral analysis of sesquiterpenes from the dried pods.  Chem Pharm Bull. 1994;  42 138-46
• 25 Ying B P, Yang P M, Zhu H R. Studies on the chemical constituents of Tussilago farfara L. I. The structure of farfaratone.  Acta Chim Sin. 1987;  45 450-5
• 26 Wang C D, Gao L JN, Mi C F, Qiao B L, Yang J, Zheng Q T. et al . Studies on the chemical constituents of Tussilago farfara L.  Acta Pharm Sin. 1989;  24 913-6
• 27 Wang W S, Gao K, Jia Z J. New eremophilenolides from Ligulariopsis shichuana .  J Nat Prod. 2002;  65 714-7
• 28 Li X Q, Gao K, Jia Z J. Eremophilenolides and other constituent from the roots of Ligularia sagitta .  Planta Med. 2003;  69 356-60
• 29 Zhao Y, Parsons S, Smart B A, Tan R X, Jia Z J, Sun H D, Rankin D WH. Eremophilane derivatives with a novel carbon skeleton from Ligularia veitchiana .  Tetrahedron. 1997;  53 6195-208
• 30 Yaoita Y, Kikuchi M. Structures of new eremophilane derivatives from the rhizomes of Petasites japonicus Maxim.  Chem Pharm Bull. 1995;  43 1738-43
• 31 Naya K, Kanazawa R, Sawada M. The photosensitized oxygenation of furanoeremophilanes I. The isomeric hydroperoxides from petasalbin and their transformations to lactones.  Bull Chem Soc Jpn. 1975;  48 3220-5
• 32 Naya K, Nogi N, Makiyama Y, Takashina H, Imagawa T. The photosensitized oxygenation of furanoeremophilanes II. The Preparation and stereochemistry of the isomeric hydroperoxides and the corresponding lactones from furnaofukinin and furanoeremophilanes.  Bull Chem Soc Jpn. 1977;  50 3002-6
• 33 Sugama K, Hayashi K, Mitsuhashi H. Eremophilenolides from Petasites japonicus .  Phytochemistry. 1985;  24 1531-5
• 34 Lin Y L, Ou J C, Chrn C F, Kuo Y H. Eremophilanes from Petasites formosanus Kitamura.  Chem Pharm Bull. 1998;  46 1807-9