Flavagline

Chemical structure of the flavagline FL3

Flavaglines are a family of natural products that are found in plants of the genus Aglaia (Meliaceae). These compounds are characterized by a cyclopenta[b]benzofuran skeleton. In 1982 King and colleagues discovered the first member of this family, rocaglamide, based on its antileukemic activity.[1] Since then, about 50 other flavaglines have been characterized. These molecules display strong insecticidal, antifungal, anti-inflammatory, neuroprotective, cardioprotective and anticancer activities.[2][3] In mouse models of cancer, flavaglines enhance the efficacy of chemotherapies[4][5] and also alleviate the cardiac adverse effect of these chemotherapies.[6]

The challenge raised by their structural complexity has attracted the attention of some organic chemists. In 1990, Barry Trost presented an enantioselective synthesis of rocaglamide in 18 steps and confirmed its absolute configuration.[7]

See also

References

  1. ↑ King, M. L.; Chiang, C. C.; Ling, H. C.; Fujita, E.; Ochiai, M.; McPhail, A. T., X-Ray crystal structure of rocaglamide, a novel antileukemic 1H-cyclopenta[b]benzofuran from Aglaia elliptifolia. Chem Commun 1992, 1150-51.
  2. ↑ Ebada, S. S.; Lajkiewicz, N.; Porco, J. A., Jr.; Li-Weber, M.; Proksch, P., Chemistry and biology of rocaglamides (= flavaglines) and related derivatives from aglaia species (meliaceae). Fortschr Chem Org Naturst 2011, 94, 1-58.
  3. ↑ Ribeiro, N.; Thuaud, F.; Nebigil, C.; Désaubry, L., Recent advances in the biology and chemistry of the flavaglines. Bioorg Med Chem 2012, in press.
  4. ↑ Bordeleau, M. E.; Robert, F.; Gerard, B.; Lindqvist, L.; Chen, S. M.; Wendel, H. G.; Brem, B.; Greger, H.; Lowe, S. W.; Porco, J. A., Jr.; Pelletier, J., Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model. J Clin Invest 2008, 118, 2651-60.
  5. ↑ Zhu, J. Y.; Giaisi, M.; Kohler, R.; Muller, W. W.; Muhleisen, A.; Proksch, P.; Krammer, P. H.; Li-Weber, M., Rocaglamide sensitizes leukemic T cells to activation-induced cell death by differential regulation of CD95L and c-FLIP expression. Cell Death Differ 2009, 16, 1289-99.
  6. ↑ Bernard, Y.; Ribeiro, N.; Thuaud, F.; Türkeri, G.; Dirr, R.; Boulberdaa, M.; Nebigil, C.; Désaubry, L. (2011). "Flavaglines Alleviate Doxorubicin Cardiotoxicity: Implication of Hsp27". PLoS ONE. 6: e25302. doi:10.1371/journal.pone.0025302.
  7. ↑ Trost, B. M.; Greenspan, P. D.; Yang, B. V.; Saulnier, M. G., An unusual oxidative cyclization. A synthesis and absolute stereochemical assignment of (−)-rocaglamide. J Am Chem Soc 1990, 112, 9022-4.


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