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Journal of the Mexican Chemical Society

Print version ISSN 1870-249X

J. Mex. Chem. Soc vol.49 n.2 México  2005




The Solid-State and Solution-State Reassigned Structures of Tagitinin A, a 3,10-Epoxy-Germacrolide from Tithonia diversifolia, and the Interconversion of 3,10-Epoxy-Germacrolide Conformational Families via a Ring-Atom Flip Mechanism


Robert Glaser*,#,a, Abraham Garcíab, María Isabel Chávezb and Guillermo Delgado*,#,b


a Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. * e-mail:

b Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, 04510 México D. F., México. * e-mail:


Received: November 28, 2004
Published on the web: April 12, 2005



Tagitinin A (2), a known 3,10-epoxy-germacrolide-6,7-trans-lactone isolated from Tithonia diversifolia, was investigated by single crystal X-ray diffraction analysis. It was found to have a 1β,4α,6α,7β,8β relative configuration which differed at C(1) from the 1α-orientation originally reported in the literature which was determined by Horeau's Rule. Analysis of the 1H NMR spectrum of 2 shows the molecule to maintain its crystallographically observed twist-chair-boat (TCB) nine-membered ring conformation in acetone-d6 solution. The twist-chair-boat/skew-chair-boat type 3 conformations of saturated/unsaturated nine-membered rings within 3,10-epoxy-germacrolides can be interconverted to the skew-chair-chair (SCC) conformation by means of a C(9) ring atom flip mechanism. As a result of this conformational change, the orientation of the C(1) atom and the C(8)-oxycarbonyl moiety are transformed from diequatorial to diaxial. The reported stereochemistry of 3,10-epoxy-germacrolide lactone structures, and the DFT B3LYP/6-31g(d) modeling findings in this work indicate that tetrahedral C(1) atoms stabilize the TCB/SCB type 3 conformations, while their trigonal counterparts stabilize the SCC conformation.

Keywords: tagitinin A, Horeau's rule, conformational interconversion, molecular modeling



Tagitinina А(2), uma 3,10-epoxi-germacrolida-6,7-trans-lactona conhecida e isolada de Tithonia diversifolia foi estudada através de difração de raios-X de monocristal. Verificou-se que a mesma apresenta a configuração relativa 1β,4α,6α,7β,8β que difere da orientação 1α em C(1) proposta originalmente na literatura e que foi determinada pelo método de Horeau. Análise do espectro de 1H-RMN de 2 em solução de d6-acetona mostra que a molécula mantém a conformação twist-chair-boat (TCB) observada cristalograficamente para o anel de 9 membros. As conformações twist-chair-boat/skew-chair-boat do tipo 3 para anéis de 9 membros saturados e insaturados dentro das 3,10-epoxi-germacrolídas podem ser convertidas à conformação skew-chair-chair (SCC) através de mecanismo de inversão de C(9) do anel. Como resultado dessa mudança conformacional, a orientação de C(1) e de C(8) da unidade oxicarbonila são transformados de diequatorial para diaxial. A estereoquímica relatada para lactonas do tipo 3,10-epoxi-germacrolida e resultados de modelagem utilizando-se DFT B3LYP/6-31g(d) indicam que os átomos C(1) tetraédricos estabilizam conformações TCB/SCB do tipo 3 enquanto que aqueles com geometria trigonal estabilizam a conformação SCC.





The authors thank M. Sc. Simón Hernández-Ortega (Instituto de Química de la UNAM) for technical assistance. Partial financial support by Consejo Nacional de Ciencia y Tecnología through a scholarship for A. G. (register: 159657), and by DGAPA-UNAM (grant IN233202) is gratefully acknowledged. Travel funds to Mexico were provided to R.G. by BGUN.



1. Horeau, A.; Tetrahedron Lett. 1961, 506; ibid. 1962, 965;         [ Links ] Horeau, A.; Kagan, H. B.; Tetrahedron 1964, 20, 2431.         [ Links ]

2. Eliel, E. L.; Wilen, S. H.; Mander, L. N.; Stereochemistry of Organic Compounds, Wiley-Interscience: New York, 1994, p. 140-142.         [ Links ]

3. Brewster, J. H. In Elucidation of Organic Structures by Physical and Chemical Methods; Bentley, K. W.; Kirby, G. W., eds.; 2nd ed., Wiley-Interscience: New York, 1972, p. 1-249, vol. IV, Part III.         [ Links ]

4. Horeau, A.; Stereochemistry, Fundamentals and Methods, Georg Thieme Publishers: Stuttgart, 1977, vol 3.         [ Links ]

5. Kupchan, S. M.; Kelsey, J. E.; Sim, G. A.; Tetrahedron Lett. 1967, 2863.         [ Links ]

6. Rogers, D.; Moss, G. P.; Neidle, S.; J. Chem. Soc. Chem. Commun. 1972, 142.         [ Links ]

7. Romo de Vivar, A.; Guerrero, C.; Díaz, E.; Ortega, A.; Tetrahedron 1970, 26, 1657;         [ Links ] It has been suggested that the actual natural source of Zexbrevin is Viguiera greggi: Delgado, G. ; Alvarez, L.; Mata, R.; Pereda-Miranda, R.; Romo de Vivar, A.; Villaseñor, J. L.; J. Nat. Prod. 1986, 49, 1165;         [ Links ] Romo de Vivar, A.; Delgado, G.; Bol. Soc. Chil. Quím. 1985, 30, 79.         [ Links ]

8. Baruah, N. C.; Sharma, R. P.; Madhusudanan, K. P.; Thyagrarajan, G.; Herz. W.; Murari, R.; J. Org. Chem. 1979, 44, 1831;         [ Links ] Sarma, J. C.; Sharma, R. P.; de Jong, R.; Stam, C. H.; Phytochemistry 1987, 26, 2406.         [ Links ]

9. Fischer, N. H.; Oliver, E. J.; Fischer, H. D.; Prog. Chem. Org. Nat. Prod. 1979, 38, 47.         [ Links ]

10. Soriano-García, M.; Toscano, R. A.; Acta Crystallogr. 1984, C40, 1425.         [ Links ]

11. Fronzek, F. R.; Lee, I-Y.; Fischer, N. H.; J. Nat. Prod. 1983, 46, 104.         [ Links ]

12. Rodríguez-Hahn, L.; Jiménez, M.; Saucedo, R.; Soriano-García, M.; Toscano, R. A.; Díaz, E.; Tetrahedron 1983, 39, 3909.         [ Links ]

13. Soriano-García, M.; Toscano, R. A.; Díaz, E.; Rodríguez-Hahn, L.; Rev. Latinoamer. Quím. 1985, 16, 112.         [ Links ]

14. Pal, R.; Kulshreshta, D. K.; Rastogi, R. P.; Indian J. Chem. 1976, 14B, 77 and 259; ibid. 1977, 15B, 208 and 533.         [ Links ] For additional studies on Tithonia diversifolia, see: Pereira, P. S.; Dias, D. A.; Vichnewski, W.; Turco Tussi Nasi, A. M.; Herz, W.; Phytochemistry 1997, 45, 1445;         [ Links ] Kuo, Y.-H.; Chen, Ch.- H. ; J. Nat. Prod. 1998, 61, 827;         [ Links ] Gu, J.-Q.; Gills, J.J.; Park, E. J.; Mata-Greenwood, E.; Hawthorne, M. E.; Axelrod, F.; Chavez, P. I.; Fong, H. H. S.; Mehta, R. G.; Pezzuto, J. M.; Kinghorn, A. D.; J. Nat. Prod. 2002, 65, 532.         [ Links ]

15. Glaser, R.; Shiftan, D.; Levi-Roso, G.; Ergaz, I.; Geresh, S.; J. Org. Chem. 2002, 67, 5486.         [ Links ]

16. Heinrich, M.; Robles, M.; West, J. A.; Ortíz de Montellano, B. R.; Rodríguez, E.; Annu. Rev. Pharmacol. Toxicol. 1998, 38, 539.         [ Links ]

17. Bijvoet, J. M.; Peerdeman, A. F.; van Brommel, A. J.; Nature (London) 1951, 168, 271.         [ Links ]

18. The authors have deposited atomic coordinates for 2 with the Cambridge Crystallographic Data Centre. The coordinates can be obtained, free of charge via retrieving.html (or from the Cambridge Crystallographic Data Centre, CCDC, 12 Union Road, Cambridge, CB2 1EZ UK; Tel: +44 1223 336408; Fax: +44 1223 336033; or e-mail:

19. Müller, N.; Ball&Stick 3.8ß3, Institut für Chemie, Johannes Kepler Universität: Linz, Austria, 2000.         [ Links ]

20. Allen, F. H. ; Acta Crystallogr. 2002, B58, 380.         [ Links ]

21. González, A. G.; Galindo, H.; Mansilla, H.; Kestermich, V. H. ; Palenzuela, J. A.; Rodríguez, M. L.; J. Nat. Prod. 1990, 53, 462.         [ Links ]

22. Macias, F. A.; Aguilar, J. M.; Molinillo, J. M. G.; Massanet, G. M. Fronczek, F. R.; Tetrahedron 1994, 50, 5439.         [ Links ]

23. Quijano, L.; Núñez, I. S.; Fronczek, F. R.; Fischer, N. H.; Phytochemistry 1997, 45, 769.         [ Links ]

24. Hayashi, T.; Nakano, T.; Kozuka, M.; McPhail, D. R.; McPhail, A. T.; Lee, K. H.; J. Nat. Prod. 1999, 62, 302.         [ Links ]

25. Sundin, A.; MacMimic 3.0, In-Star Software: Lund, Sweden, 1996 [         [ Links ]now Department of Bioorganic Chemistry, Lund Technische Hochsuhle: Lund, Sweden].

26. Gaussian-98W, revision A-7; Gaussian Inc.: Pittsburgh, PA, 1998.         [ Links ]

27. Herz, W.; Blount, J. F.; J. Org. Chem. 1978, 43, 1268.         [ Links ]

28. Bruno, I. J.; Cole, J. C.; Edgington, P. R.; Kessler, M.; Macrae, C. F.; McCabe, P.; Pearson, J.; Taylor, R.; Acta Crystallogr. 2002, B58, 389.         [ Links ]

29. CSChemDraw Ultra 5.0; CambridgeSoft: Cambridge, MA, 1999;         [ Links ] Chem3D Pro 5.0; CambridgeSoft: Cambridge, MA, 1999.         [ Links ]

30. Anet, F. A. L.; Tetrahedron Lett. 1990, 31, 2125.         [ Links ]

31. Dale, J.; Stereochemistry and Conformational Analysis, Universitetsforlaget/Verlag Chemie: Oslo/New York, 1978, p. 206.         [ Links ]

32. Herz, W.; Goedken, V. L.; J. Org. Chem. 1982, 47, 2798.         [ Links ]

33. Le Quesne, P. W.; Menachery, M. D.; Pastore, M. P.; Kelley, C. J.; Brennan, T. F.; Onan, K. D.; Raffauf, R. F.; Weeks, C. M.; J. Org. Chem. 1982, 47, 1519.         [ Links ]

34. Manchand, P. S.; Todaro, L. J.; Cordell, G. A.; Soejarto, D. D.; J. Org. Chem. 1983, 48, 4388.         [ Links ]

35. Lee, I.-Y.; Fronczek, F. R.; Malcolm, A.; Fischer, N. H.; Urbatsch, L. E.; J. Nat. Prod. 1982, 45, 311.         [ Links ]

36. Fischer, N. H.; Lee, I.-Y.; Fronczek, F. R.; Chiari, G.; Urbatsch, L. E.; J. Nat. Prod. 1984, 47, 419.         [ Links ]

37. Castañeda-Acosta, J.; Ober, A. G.; Fronczek, F. R.; Fischer, N. H.; Chiari, G.; J. Chem. Cryst. 1997, 27, 641.         [ Links ]

38. Herz, W.; Blount, J. F.; J. Org. Chem. 1978, 43, 4887.         [ Links ]

39. Gershenzon, J.; Liu, Y.-L.; Mabry, T. J.; Korp, J. D.; Bernal, I.; Phytochemistry 1984, 23, 1281.         [ Links ]

40. Rodríguez, J. D.; Perales, A.; Rodríguez-Ubis, J. C.; Vázquez, P.; Borges, J.; J. Nat. Prod. 1995, 58, 446.         [ Links ]

41. Budzelaar, P. H. M.; Gnmr4.1; Cherwell Scientific Ltd.: Oxford, U.K., 1999.         [ Links ]

42. Goto, H.; Osawa, E.; J. Am. Chem. Soc. 1989, 111, 8950.         [ Links ]

43. Hendrickson, J. B.; J. Am. Chem. Soc. 1967, 89, 7047.         [ Links ]

44. Glaser, R.; Michel, A.; Drouin, M.; Can. J. Chem. 1990, 68, 1128.         [ Links ]

45. Glaser, R.; Novoselsky, A.; Shiftan, D.; Drouin, M.; J. Org. Chem. 2000, 65, 6345.         [ Links ]

46. SMART (5.625); Bruker AXS Inc.: Madison, WI, 2000.         [ Links ]

47. Sheldrick, G. M.; SHELXTL97; An Integrated System for Solving, Refining and Displaying Crystal Structures from Diffraction Data, University of Göttingen: Germany, 1997.         [ Links ]

48. International Tables for X-ray Crystallography, Kynoch Press: Birmingham, vol IV, 1974.         [ Links ]



# Dedicated to Prof. Kurt Mislow on the occassion of his 80th birthday and to Prof. Alfonso Romo de Vivar, for his 50 years of research at the Instituto de Química, UNAM. "...his wisdom shall endure..." Pirke Aboth, chapter III, verse 12.

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