7058
C. Le Floch et al. / Bioorg. Med. Chem. Lett. 21 (2011) 7054–7058
9. Bazin, S.; Feray, L.; Vanthuyne, N.; Siri, D.; Bertrand, M. P. Tetrahedron 2007, 63,
77.
10. Kim, H.-C.; Park, O.-S. Tetrahedron: Asymmetry 2008, 19, 896.
11. Amador, M.; Ariza, X.; Garcia, J.; Ortiz, J. J. Org. Chem. 2004, 69, 8172.
12. For a recent review on the synthesis of paraconic acids, see: Bandichhor, R.;
Nosse, B.; Reiser, O. Top. Curr. Chem. 2005, 243, 43.
13. Murta, M. M.; De Azevedo, M. B. M.; Greene, A. E. J. Org. Chem. 1993, 58, 7537.
14. Böhm, C.; Reiser, O. Org. Lett. 2001, 3, 1315.
15. Müller, K. Appl. Microbiol. Biotechnol. 2001, 56, 9.
range of functions compatible with the process. The biological
activities of the final compounds have been evaluated against a
representative set of cancer cell lines (KB, HCT116, MCF7 and
HL60). One of the molecules proves to exhibit a promising antitu-
mor activity with IC50s in the 10À7–10À6 M range. Additional as-
says on an extended panel of cancer cell lines (PC3, SK-OV3 and
MCF7R and HL60R) indicate very similar cytotoxicities. Current
works are devoted to a deeper investigation of the structure–
activity relationship and the mechanism of action in order to either
obtain a global increase of the cytotoxic activities or provide an
optimized specific cellular growth inhibition against targeted
cancer cell lines.
16. Berti, F.; Felluga, F.; Forzato, C.; Furlan, G.; Nitti, P.; Pitacco, G.; Valentin, E.;
Barros, M. T. Tetrahedron: Asymmetry 2006, 17, 2344.
17. Jacobine, A. M.; Lin, W.; Walls, B.; Zercher, C. K. .J. Org. Chem. 2008, 73, 7409.
18. Li, Y.; Zhao, Z.-A.; He, H.; You, S.-L. Adv. Synth. Catal. 2008, 350, 1885.
19. Greszler, S. N.; Johnson, J. S. Angew. Chem. Int. Ed. 2009, 48, 3689.
20. Shono, T.; Hamaguchi, H.; Nishiguchi, I.; Sasaki, M.; Miyamoto, T.; Miyamoto,
M.; Fujita, S. Chem. Lett. 1981, 1217.
21. D’Onofrio, F.; Margarita, R.; Parlanti, L.; Piancatelli, G.; Sbraga, M. Chem.
Commun. 1998, 185.
22. Méou, A.; Lamarque, L.; Brun, P. Tetrahedron Lett. 2002, 43, 5301.
23. Zhu, J.; Bienaymé, H. Multicomponent Reactions; Wiley-VCH: Weinheim, 2005.
Acknowledgments
Financial support of this work by the CNRS and the University
Paris-Est (PhD Grant) is gratefully acknowledged.
24. The synthesis of monosubstituted lactones (N-Carbamoylmethyl-a-
aminobutyrolactones) by the Ugi multicomponent reaction has been
reported, see: Park, S. J.; Keum, G.; Kang, S. B.; Koh, H. Y.; Kim, Y. Tetrahedron
Lett. 1998, 39, 7109.
References and notes
25. For the synthesis of
a-methylene-c-butyrolactones starting from preformed
alkylcopper reagents, Michael acceptors and aldehydes, see: Sidduri, A.;
Knochel, P. J. Am. Chem. Soc. 1992, 114, 7579.
26. Le Gall, E.; Haurena, C.; Sengmany, S.; Martens, T.; Troupel, M. J. Org. Chem.
2009, 74, 7970.
1. Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Int. Ed. Engl. 1985, 24, 94.
2. Fischer, N. H.; Lu, T.; Cantrell, C. L.; Castaneda-Acosta, J.; Quijano, L.; Franzblau,
S. Phytochemistry 1998, 49, 559.
27. Le Floch, C.; Le Gall, E.; Léonel, E.; Koubaa, J.; Martens, T.; Retailleau, P. Eur. J.
Org. Chem. 2010, 27, 5279.
3. Wang, T.-C.; Lee, K.-H.; Chen, Y.-L.; Liou, S.-S.; Tzeng, C.-C. Bioorg. Med. Chem.
Lett. 1998, 8, 2773.
28.
A related strategy has been applied successfully by Montgomery to the
4. Higuchi, Y.; Shimoma, F.; Ando, M. J. Nat. Prod. 2003, 66, 810.
5. Hughes, M. A.; McFadden, J. M.; Townsend, C. A. Bioorg. Med. Chem. Lett. 2005,
15, 3857.
6. Petragnani, N.; Ferraz, H. M. C.; Silva, G. V. J. Synthesis 1986, 157.
7. Pohmakotr, M.; Harnying, W.; Tuchinda, P.; Reutrakul, V. Helv. Chim. Acta 2002,
85, 3792.
synthesis of b-hydroxyester derivatives, see: (a) Subburaj, K.; Montgomery, J. J.
Am. Chem. Soc. 2003, 125, 11210; (b) Chrovian, C.; Montgomery, C. J. Org. Lett.
2007, 9, 537.
29. All reactions were monitored by Gas Chromatography.
30. Thuaud, F.; Bernard, Y.; Turkeri, G.; Dirr, R.; Aubert, G.; Cresteil, T.; Baguet, A.;
Tomasetto, C.; Svitkin, Y.; Sonenberg, N.; Bebigil, C. G.; Desaubry, L. J. Med.
Chem. 2009, 52, 5176.
8. Blanc, D.; Madec, J.; Popowyck, F.; Ayad, T.; Phansavath, P.; Ratovelomanana,
V.; Genêt, J.-P. Adv. Synth. Catal. 2007, 349, 943.