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
Keywords:
Tagitinin A, Horeau’s rule, conformational interconversion, molecular modelingAbstract
Abstract. 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) ninemembered 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 .
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References
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7. Romo de Vivar, A.; Guerrero, C.; Díaz, E.; Ortega, A.; Tetrahedron 1970, 26, 1657; 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; Romo de Vivar, A.; Delgado, G.; Bol. Soc. Chil. Quím. 1985, 30, 79.
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10. Soriano-García, M.; Toscano, R. A.; Acta Crystallogr. 1984, C40, 1425.
11. Fronzek, F. R.; Lee, I-Y.; Fischer, N. H.; J. Nat. Prod. 1983, 46, 104.
12. Rodríguez-Hahn, L.; Jiménez, M.; Saucedo, R.; Soriano-García, M.; Toscano, R. A.; Díaz, E.; Tetrahedron 1983, 39, 3909.
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14. Pal, R.; Kulshreshta, D. K.; Rastogi, R. P.; Indian J. Chem. 1976, 14B, 77 and 259; ibid. 1977, 15B, 208 and 533. 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; Kuo, Y.-H.; Chen, Ch.-H.; J. Nat. Prod. 1998, 61, 827; 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.
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18. The authors have deposited atomic coordinates for 2 with the Cambridge Crystallographic Data Centre. The coordinates can be obtained, free of charge via www.ccdc.cam.ac.uk/conts/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: deposit@ccdc.cam.ac.uk).
19. Müller, N.; Ball&Stick 3.8β3, Institut für Chemie, Johannes Kepler Universität: Linz, Austria, 2000.
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22. Macias, F. A.; Aguilar, J. M.; Molinillo, J. M. G.; Massanet, G. M. Fronczek, F. R.; Tetrahedron 1994, 50, 5439.
23. Quijano, L.; Núñez, I. S.; Fronczek, F. R.; Fischer, N. H.; Phytochemistry 1997, 45, 769.
24. Hayashi, T.; Nakano, T.; Kozuka, M.; McPhail, D. R.; McPhail, A. T.; Lee, K. H.; J. Nat. Prod. 1999, 62, 302.
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31. Dale, J.; Stereochemistry and Conformational Analysis, Universitetsforlaget/Verlag Chemie: Oslo/New York, 1978, p. 206.
32. Herz, W.; Goedken, V. L.; J. Org. Chem. 1982, 47, 2798.
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.
34. Manchand, P. S.; Todaro, L. J.; Cordell, G. A.; Soejarto, D. D.; J. Org. Chem. 1983, 48, 4388.
35. Lee, I.-Y.; Fronczek, F. R.; Malcolm, A.; Fischer, N. H.; Urbatsch, L. E.; J. Nat. Prod. 1982, 45, 311.
36. Fischer, N. H.; Lee, I.-Y.; Fronczek, F. R.; Chiari, G.; Urbatsch, L. E.; J. Nat. Prod. 1984, 47, 419.
37. Castañeda-Acosta, J.; Ober, A. G.; Fronczek, F. R.; Fischer, N. H.; Chiari, G.; J. Chem. Cryst. 1997, 27, 641.
38. Herz, W.; Blount, J. F.; J. Org. Chem. 1978, 43, 4887.
39. Gershenzon, J.; Liu, Y.-L.; Mabry, T. J.; Korp, J. D.; Bernal, I.; Phytochemistry 1984, 23, 1281.
40. Rodríguez, J. D.; Perales, A.; Rodríguez-Ubis, J. C.; Vázquez, P.; Borges, J.; J. Nat. Prod. 1995, 58, 446.
41. Budzelaar, P. H. M.; Gnmr 4.1; Cherwell Scientific Ltd.: Oxford, U.K., 1999.
42. Goto, H.; Osawa, E.; J. Am. Chem. Soc. 1989, 111, 8950.
43. Hendrickson, J. B.; J. Am. Chem. Soc. 1967, 89, 7047.
44. Glaser, R.; Michel, A.; Drouin, M.; Can. J. Chem. 1990, 68, 1128.
45. Glaser, R.; Novoselsky, A.; Shiftan, D.; Drouin, M.; J. Org. Chem. 2000, 65, 6345.
46. SMART (5.625); Bruker AXS Inc.: Madison, WI, 2000.
47. Sheldrick, G. M.; SHELXTL97; An Integrated System for Solving, Refining and Displaying Crystal Structures from Diffraction Data, University of Göttingen: Germany, 1997.
48. International Tables for X-ray Crystallography, Kynoch Press: Birmingham, vol IV, 1974.
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