Aplysqualenols A and B: Squalene-derived polyethers with antitumoral and antiviral activity from the Caribbean Sea slug aplysia dactylomela

European Journal of Organic Chemistry

Volumn , Issue 31, 2009, Pages 5327-5336

  Vera, Brunilda ^a   Rodríguez, Abimael D ^a   Avilés, Edward ^a   Ishikawa, Yasuyuki ^a  

^a UNIVERSITY OF PUERTO RICO   (Puerto Rico)

Author keywords

Apfysia dactylomela; Aplysqualenols A and B; Biological activity; Natural products; Polyethers; Structure elucidation

Indexed keywords

EID: 70450185925     PISSN: 1434193X     EISSN: 10990690     Source Type: Journal    
DOI: 10.1002/ejoc.200900775     Document Type: Article

References (33)

1. J.W. Blunt, B. R. Copp, W.-P. Hu, M. H. G. Munro, P.T. Northcote, M. R. Prinsep, Nat. Prod. Rep. 2009, 26, 170-244, and previous articles in this series.
2. a) M. Wessels, G. M. König, A. D. Wright, J. Nat. Prod. 2000, 67, 920-928;
3. b) T Dias, I. Brito, L. Moujir, N Paiz, J. Darias, M. Cueto, J. Nat. Prod. 2005, 68, 1677-1679;
4. c) E. Manzo, M. L. Ciavatta, M. Gavagnin, R. Puliti, E. Mollo, Y W Guo, C. A. Mattia, L. Mazzarella, G. Cimino, Tetrahedron 2005, 61, 7456-7460.
5. N. R. Ferrigni, B. N. Meyer, J. E. Putnam, L. B. Jacobsen, D. E. Nichols, J. L. McLaughlin, J. Med. Plant Res. 1982, 45, 31-34.
6. J. J. Fernández, M. L. Souto, M. Norte, Nat. Prod Rep. 2000, 17, 235-246.
7. J.W. Blunt, M. P. Hartshorn, T.J. McLennan, M. H. G Munro, W T Robinson, S. C Yorke, Tetrahedron Lett. 1978, 19, 69-72.
8. S. Sakemi, T Higa, C. W. Jefford, G. Bernardinelli, Tetrahedron Lett. 1986, 27, 4287-4290.
9. E. Manzo, M. Gavagnin, G Bifulco, P. Cimino, S. Di Micco, M. L. Ciavatta, Y. W. Guo, G. Cimino, Tetrahedron 2007, 63, 9970-9978.
10. R. E. Pfeffer, K. M. Valentine, F. W Parrish, J. Am. Chem. Soc. 1979, 101, 1265-1274.
11. 13C NMR chemical shifts about the 2,7-dioxabicyclo[4.4.0]decane ring. In 1, for instance, C27 resonates at δ = 14.8 ppm, whereas all related congeners with the usual C14 (R*) configuration show this signal at ô > 20 ppm. This modification in stereochemistry also causes the C11 resonance to shift downfield (i.e., from <5 = 76.3 ppm in 7 to <5 = 80.8 ppm in 1). A reversal in relative stereochemistry at C14 also causes the nearby C28 methyl group in 1 to resonate at <5 = 18.1 ppm rather than at <5 = 22.9 or 23.0 ppm as seen in 5 and 7, respectively, in spite of the fact that all three compounds have the C15 (R*) configuration.
12. The minimum-energy configuration for 1 was identified by a Monte Carlo conformational search with the MMFF force field as implemented in the Spartan 04 software package (Wavefunction Inc., Irvine, CA).
13. a) R. Hohenberg, W. Kohn, Phys. Rev. 1964, 136, B864-B871;
14. b) W Kohn, L. J. Sham, Phys. Rev. 1965, 140, All33-Al138.
15. We attempted to confirm the proposed structure of aplysqualenol A (1) by X-ray crystallography through chemical transformation into a crystalline derivative. Thus, after heatingof a mixture of 1 and 4-bromophenyl isocyanate in toluene for 3 h, the desired carbamate was obtained in excellent yield, but it failed to crystallize in all of the solvents tried.
16. S. Porto, J. Durán, J. M. Seco, E. Quiñoá, R. Riguera, Org. Lett. 2003, 5, 2979-2982.
17. The procedure is based on the binding of MTPA or MPA to a resin in such a way that, when attacked by the chiral molecule (i.e., compound 1), the reagent part acts as an electrophile and liberates the corresponding ester derivative into the solution, while the solid matrix behaves as the leaving group. The NMR spectra of the expected derivatives are then obtained without any separation, workup, or manipulation.
18. 0C points to the fact that the hydrogen bonds between the donor hydrogen atoms and the acceptor atoms in 2 have less than ideal geometry.
19. Spartan 04 for Macintosh, Wavefunction Inc., Irvine, CA.
20. M. J. Frisch, G. W Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery Jr, T. Vreven, K. N Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomáši, V Barone, B. Mennucci, M. Cossi, G. Scalmani, N Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. R Hratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, R Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, R Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, R. M. W. Gill, B. Johnson, W. Chen, M.W. Wong, C. González, J. A. Pople, Gaussian 03, Revision C.02, Gaussian, Inc., Wallingford CT, 2004.
21. a) R Cimino, L. Gómez-Paloma, D. Duca, R. Riccio, G Bifulco, Magn. Reson. Chem. 2004, 42, S26-S33;
22. b) G. Bifulco, R Dambruoso, L. Gómez-Paloma, R. Riccio, Chem. Rev. 2007, 107, 3744-3779.
23. a) H. Kigoshi, M. Ojika, Y. Shizuri, H. Niwa, K. Yamada, Tetrahedron Lett. 1982, 23, 5413-5414;
24. b) L. De Napoli, E. Fattorusso, S. Magno, L. Mayol, Phytochemistry 1982, 21, 782-784.
25. 3 group could be explained by methanolysis at the C22-C23 epoxide, implying that the genesis of this functionality in 1 and 2 could be artifactual.
26. C.N. Rogers, R. DeNys, T.S. Charlton, R.D. Steinberg, J. Chem. Ecol. 2000, 26, 721-743.
27. Differences in cytotoxicity detected among compounds of this class have been related to the different conformations adopted by the C14 flexible side chain, see: M. Norte, J. J. Fernández, M. L. Souto, J. A. Gavin, M. D. García-Grávalos, Tetrahedron 1997, 53, 3173-3178.
28. -1 more stable than its corresponding C14 epimer.
29. Primary Epstein-Barr virus infection in childhood is usually mild but in later life usually manifests as infectious mononucleosis.
30. a) J. J. Sims, G. H. Y Lin, R. M. Wing, Tetrahedron Lett. 1974, 15, 3487-3490;
31. b) A. G González, J. Darias, A. Diaz, J. D. Fourneron, J. D. Martin, C. Pérez, Tetrahedron Lett. 1976, 17, 3051-3054.
32. L. A. Collins, S. G Franzblau, Antimicrob. Agents Chemother. 1997, 41, 1004-1009.
33. Y. Corbett, L. Herrera, J. González, L. Cubilla, T. Capson, R. D. Colley, T. A. Kursar, L. I. Romero, E. Ortega-Barria, J. Trop. Med. Hyg. 2004, 70, 119-124.