Flavagline
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.{{cite journal | last1 = King | first1 = M. L. | last2 = Chiang | first2 = C. C. | last3 = Ling | first3 = H. C. | last4 = Fujita | first4 = E. | last5 = Ochiai | first5 = M. | last6 = McPhail | first6 = A. T. | title = X-Ray crystal structure of rocaglamide, a novel antileukemic 1H-cyclopenta[b]benzofuran from Aglaia elliptifolia | journal = J Chem Soc Chem Commun | volume = 1982 | pages = 1150–1151 }} Since then, about 50 other flavaglines have been characterized. These molecules display strong insecticidal, antifungal, anti-inflammatory, neuroprotective, cardioprotective and anticancer activities.{{cite journal | last1 = Ebada | first1 = S. S. | last2 = Lajkiewicz | first2 = N. | last3 = Porco | first3 = J. A. Jr. | last4 = Li-Weber | first4 = M. | last5 = Proksch | first5 = P. | year = 2011 | title = Chemistry and biology of rocaglamides (= flavaglines) and related derivatives from aglaia species (meliaceae) | journal = Fortschr Chem Org Naturst | series = Fortschritte der Chemie organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products | volume = 94 | pages = 1–58 | doi = 10.1007/978-3-7091-0748-5_1 | pmid = 21833837 | pmc = 4157394 | isbn = 978-3-7091-0747-8 }}Ribeiro, N.; Thuaud, F.; Nebigil, C.; Désaubry, L., Recent advances in the biology and chemistry of the flavaglines. Bioorg Med Chem 2012, in press. In mouse models of cancer, flavaglines enhance the efficacy of chemotherapies{{cite journal | last1 = Bordeleau | first1 = M. E. | last2 = Robert | first2 = F. | last3 = Gerard | first3 = B. | last4 = Lindqvist | first4 = L. | last5 = Chen | first5 = S. M. | last6 = Wendel | first6 = H. G. | last7 = Brem | first7 = B. | last8 = Greger | first8 = H. | last9 = Lowe | first9 = S. W. | last10 = Porco | first10 = J. A. Jr. | last11 = Pelletier | first11 = J. | year = 2008 | title = Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model | doi = 10.1172/JCI34753 | journal = J Clin Invest | volume = 118 | issue = 7 | pages = 2651–60 |pmc=2423864 | pmid=18551192| url = http://repository.cshl.edu/27632/1/Lowe%20Journal%20of%20Clinical%20Investigation%202008.pdf }}{{cite journal | last1 = Zhu | first1 = J. Y. | last2 = Giaisi | first2 = M. | last3 = Kohler | first3 = R. | last4 = Muller | first4 = W. W. | last5 = Muhleisen | first5 = A. | last6 = Proksch | first6 = P. | last7 = Krammer | first7 = P. H. | last8 = Li-Weber | first8 = M. | year = 2009 | title = Rocaglamide sensitizes leukemic T cells to activation-induced cell death by differential regulation of CD95L and c-FLIP expression | journal = Cell Death Differ | volume = 16 | issue = 9 | pages = 1289–99 | doi=10.1038/cdd.2009.42| pmid = 19373244 | doi-access = free }} and also alleviate the cardiac adverse effect of these chemotherapies.{{cite journal|last1=Bernard|first1=Y.|last2=Ribeiro|first2=N.|last3=Thuaud|first3=F.|last4=Türkeri|first4=G.|last5=Dirr|first5=R.|last6=Boulberdaa|first6=M.|last7=Nebigil|first7=C.|last8=Désaubry|first8=L.|title=Flavaglines Alleviate Doxorubicin Cardiotoxicity: Implication of Hsp27|journal=PLoS ONE|volume=6|page=e25302|year=2011|issue=10|doi=10.1371/journal.pone.0025302|pmid=22065986|pmc=3204970|bibcode=2011PLoSO...625302B|doi-access=free}}
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.{{cite journal | last1 = Trost | first1 = B. M. | last2 = Greenspan | first2 = P. D. | last3 = Yang | first3 = B. V. | last4 = Saulnier | first4 = M. G. | year = 1990 | title = An unusual oxidative cyclization. A synthesis and absolute stereochemical assignment of (−)-rocaglamide | journal = J Am Chem Soc | volume = 112 | issue = 24 | pages = 9022–4 | doi=10.1021/ja00180a081}}