The acid-catalyzed cyclization of mono epoxides of cnicin acetonide (3) was investigated. Several 6,12-eudesmanolides were obtained, and their stereochemistry established by extensive spectroscopic analyses. Chemical correlations also led to the assignment of the absolute configuration of 1β,10α-epoxy-salonitenolide (13), a previously isolated natural product. The cytotoxic activities of some compounds were determined against A549 and MCF-7 tumor cell lines. The esterified germacranolides 2–6 were selectively cytotoxic against the MCF-7 breast cancer cell line.
FischerNH, OliverEJ, FischerHD. (1979) The biogenesis and chemistry of sesquiterpene lactones. Progress in the Chemistry of Organic Natural Products, 38, 48–390;
3.
MarcoJA, Sanz-CerveraJF, Garcia-LlisoV, DomingoLR, CardaM, RodriguezS, Lopez-OrtizF, LexJ. (1995) Influence of conformational factors on acid-catalyzed cyclizations of germacranolides: molecular structure of the cyclization products of gallicin and 8α-hydroxygallicin (shonachalin A). Liebigs Annales, 1837–1841;
4.
AzarkenR, GuerraFM, Moreno-DoradoFJ, JorgeZD, MassanetGM. (2008) Substituent effects in the transannular cyclizations of germacranes. Synthesis of 6-epi-costunolide and five natural steiractinolides. Tetrahedron, 64, 10896–10905;
5.
MinnaardAJ, WijnbergJBPA, de GrootA. (1997) About the chiral stability of germacrene B and the biomimetic synthesis of guaiane sesquiterpenes. Journal of Organic Chemistry, 62, 7346–7350.
6.
KaldybaevaK, EdilbaevaTT, TurdybekovKM. (2000) Effect of epoxidation of carbocyclic double bonds on conformational flexibility of 1(10)E,4E-germacranolides. Chemistry of Natural Compounds, 36, 497–500.
7.
MaggioA, BaroneG, BrunoM, DucaD, RosselliS. (2005) Conformational analysis and DFT calculation of 8α-hydroxy-germacradiene-6,12-olide derivatives. Journal of Physical Organic Chemistry, 18, 1116–1122.
8.
BrunoM, FazioC, PaternostroMP, DiazJG, HerzW. (1995) Sesquiterpene lactones and other constituents of Centaurea napifolia. Planta Medica, 61, 374–375;
9.
BrunoM, RosselliS, MaggioA, RaccugliaRA, SenatoreF, NapolitanoF. (2003) Antibacterial evaluation of cnicin and some natural and semisynthetic derivatives. Planta Medica, 63, 277–281;
10.
BrunoM, RosselliS, MaggioA, RaccugliaRA, BastowKF, WuCC, LeeKH. (2005) Cytotoxic activity of some natural and synthetic sesquiterpene lactones. Planta Medica, 71, 1176–1178;
11.
BarreroAF, OltraJE, RodriguezI, BarraganA, GravelosDG, RuizP. (1995) Lactones from species of Centaurea. Cytotoxic and antimicrobial activities. Fitoterapia, 66, 227–230;
12.
RosselliS, MaggioA, RaccugliaRA, BrunoM. (2003) Rearrangement of germacranolides. Synthesis and absolute configuration of elemane and heliangolane derivatives from cnicin. European Journal of Organic Chemistry, 2690–2694;
13.
BarreroAF, OltraJE, MoralesV, AlvarezM. (1997) Biomimetic cyclization of cnicin to malacitanolide, a cytotoxic eudesmanolide from Centaurea malacitana. Journal of Natural Products, 60, 1034–1035;
14.
BohlmannF, JakupovicJ, AhmedM, SchusterA. (1983) Sesquiterpene lactones and other constituents from Schistostephium species. Phytochemistry, 22, 1623–1636.
AdekenovSM, GatilovYV, BagryanskayaYI, RalduginVA. (1993) Absolute configuration of asymmetric center in the side chain and conformation of the cyclic part of cnicin. Sibirskii Khimicheskii Zhurnal, 76–79;
17.
BarreroAF, Sanchez JFJ. F., RodriguezI I., SoriaC.SanzC. (1988) Germacranolidas de Centaurea malacitana. Anales de Quimica, 84, 344–347.