A new, reliable, and convenient protection-free one-pot method for the synthesis of aureusidin (1) is described. The present synthetic approach involves the condensation of 4,6-dihydroxybenzofuranone with 3,4-dihydroxybenzaldehyde in the presence of concentrated HCl to afford aureusidin (1) in good yield with high purity. This procedure offers a short and simple route for the preparation of aureusidin (1), a bioactive natural product from several vegetal species, as well as for synthesis of other aurones.
MiddletonE.J. (1998) Effect of plant flavonoids on immune and inflammatory cell function. Advances in Experimental Medicine and Biology, 439, 175–182.
2.
(a) ChengH., ZhangL., LiuY., ChenS., ChengH., LuX., ZhengZ., ZhouG.C. (2010) Design, synthesis and discovery of 5-hydroxyaurone derivatives as growth inhibitors against HUVEC and some cancer cell lines. European Journal of Medicinal Chemistry, 45, 5950–5957;(b) Sim HM, Lee CY, Ee PLR, Go ML. (2008) Dimethoxyaurones: potent inhibitors of ABCG2 (breast cancer resistance protein). European Journal of Pharmaceutical Sciences, 35, 293–306; (c) Sim HM, Loh KY, Yeo WK, Lee CY, Go ML. (2011) Aurones as modulators of ABCG2 and ABCB1: synthesis and structure-activity relationships. ChemMedChem, 6, 713–724.
3.
BandgarB.P., PatilS.A., KorbadB.L., BiradarS.C., NileS.N., KhobragadeC.N. (2010) Synthesis and biological evaluation of a novel series of 2,2-bisaminomethylated aurone analogues as anti-inflammatory and antimicrobial agents. European Journal of Medicinal Chemistry, 45, 3223–3227.
4.
(a) VenkateswarluS., PanchagnulaG.K., GottumukkalaA.L., SubbarajuG.V. (2007) Synthesis, structural revision, and biological activities of 4′-chloroaurone, a metabolite of marine brown alga Spatoglossum variabile. Tetrahedron, 63, 6909–6914;(b) Detsi A, Majdalani M, Kontogiorgis CA, Hadjipavlou-Litina D, Kefalas P. (2009) Natural and synthetic 2′-hydroxy-chalcones and aurones: synthesis, characterization and evaluation of the antioxidant and soybean lipoxygenase inhibitory activity. Bioorganic & Medicinal Chemistry, 17, 8073–8085.
5.
CliffordH.T., HarborneJ.B. (1969) Comparative biochemistry of the flavonoids. IX. Flavonoid pigmentation in the sedges (Cyperaceae). Phytochemistry, 8, 123–126.
6.
Auf'mkolkM., KoehrleJ. (1986) Inhibition of rat liver iodothyronine deiodinase. Interaction of aurones with the iodothyronine ligand-binding site. The Journal of Biological Chemistry, 261, 11623–11630.
LawrenceN.J., RennisonD., McGownA.T., HadfieldJ.A. (2003) The total synthesis of an aurone isolated from Uvaria hamiltonii: Aurones and flavones as anticancer agents. Bioorganic & Medicinal Chemical Letter, 13, 3759–3763.
9.
NishidaJ., KawatabaJ. (2006) DPPH radical scavenging reaction of hydroxy- and methoxychalcones. Bioscience, Biotechnology, and Biochemistry, 70, 193–202.
10.
(a) LévaiA., TókésA.L. (1982) Synthesis of aurones by the oxidative rearrangement of 2′-hydroxychalcones with thallium (III) nitrate. Synthetic Communication, 12, 701–707;(b) Garcia H, Iborra S, Primo J, Miranda MA. (1986) 6-Endo-Dig vs. 5-Exo-Dig ring closure in o-hydroxy-arylphenylethynyl ketones. A new approach to the synthesis of flavones and aurones. Journal of Organic Chemistry, 51, 4432–4436; (c) Lmafuku K, Honda M, McOmie JF. (1987) Cyclodehydrogenation of 2′-hydroxychalcones with DDQ: a simple route for flavones and aurones. Synthesis, 199–201; (d) Sekizaki H. (1988) Synthesis of 2-benzylidene-3-(2H)-benzofuran-3-ones (aurones) by oxidation of 2′-hydroxychalcones with mercury(II) acetate. Bulletin of the Chemical Society of Japan, 61, 1407–1409; (e) Brennan CM, Johnson CD, McDonnell PD. (1989) Ring closure to ynone systems: 5- and 6-endo- and -exo-dig modes. Journal of the Chemical Society, Perkin Transactions 2, 957–961; (f) An ZW, Catellani M, Chiusoli GP. (1990) Palladium-catalyzed synthesis of aurone from salicyloyl chloride and phenylacetylene. Journal of Organometallic Chemistry, 397, 371–373; (g) Jong TT, Leu SJ. (1990) Intramolecular cyclisation catalysed by silver(I) ion; a convenient synthesis of aurones. Journal of the Chemical Society, Perkin Transactions 1, 423–424; (h) Thakkar K, Cushman M. (1995) A novel oxidative cyclization of 2′-hydroxychalcones to 4,5-dialkoxyaurones by thallium(III) nitrate. Journal of Organic Chemistry, 60, 6499–6510; (i) Bose G, Mondal E, Khan AT, Bordoloi MJ. (2001) An environmentally benign synthesis of aurones and flavones from 2′-acetoxychalcones using n-tetrabutylammonium tribromide. Tetrahedron Letters, 42, 8907–8909; (j) Harkat H, Blanc A, Weibel JM, Pale P. (2008) Versatile and expeditious synthesis of aurones via AuI-catalyzed cyclization. Journal of Organic Chemistry, 73, 1620–1623.
11.
(a) VarmaR.S., VarmaM. (1992) Alumina-mediated condensation. A simple synthesis of aurones. Tetrahedron Letters, 33, 5937–5940;(b) Schoepfer J, Fretz H, Chaudhuri B, Muller L, Seeber E, Meijer L, Lozach O, Vangrevelinghe E, Furet P. (2002) Journal of Medicinal Chemistry, 45, 1741–1747; (c) Venkateswarlu S, Panchagnula GK, Subbaraju GV. (2004) Synthesis and antioxidative activity of 3′4′,6,7-tetrahydroxyaurone, a metabolite of Bidens frondasa. Bioscience, Biotechnology, and Biochemistry, 68, 2183–2185; (d) Bolek D, Gütschow M. (2005) Preparation of 4,6,3′,4′-tetrasubstituted aurones via aluminium oxide-catalyzed condensation, Journal of Heterocyclic Chemistry, 42, 1399–1403; (e) Zhao X, Liu J, Xie Z, Li Y. (2012) A one-pot synthesis of aurones from substituted acetophenones and benzaldehydes: A concise synthesis of aureusidin. Synthesis 44, 2217–2224; (f) Nishida J, Kawataba J. (2006) DPPH radical scavenging reaction of hydroxy- and methoxychalcones. Bioscience, Biotechnology, and Biochemistry, 70, 193–202; (g) Okombi S, Rival D, Bonnet S, Mariotte AM, Perrier E, Boumendjel A. (2006) Discovery of benzylidenebenzofuran-3(2H)-one (aurones) as inhibitors of tyrosinase derived from human melanocytes. Journal of Medicinal Chemistry, 49, 329–333; (h) Morimoto M, Fukumoto H, Nozoe T, Hagiwara A, Komai K. (2007) Synthesis and insect antifeedant activity of aurones against Spodoptera litura larvae. Journal of Agricultural and Food Chemistry, 55, 700–705; (i) Lee CY, Chew EH, Go ML. (2010) Functionalized aurones as inducers of NAD(P)H: quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR. European Journal of Medicinal Chemistry, 45, 2957–2971; (j) Cheng H, Zhang L, Liu Y, Chen S, Cheng H, Lu X, Zheng Z, Zhou GC. (2010) Design, synthesis and discovery of 5-hydroxyaurone derivatives as growth inhibitors against HUVEC and some cancer cell lines. European Journal of Medicinal Chemistry, 45, 5950–5957; (k) Haudecoeur R, Ahmed-Belkacem A, Yi W, Fortuné A, Brillet R, Belle C, Nicolle E, Pallier C, Pawlotsky JM, Boumendjel A. (2011) Discovery of naturally occurring aurones that are potent allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase. Journal of Medicinal Chemistry, 54, 5395–5402.
12.
XuS., ShangM.Y., LiuG.X., XuF., WangX., ShouC.C., CaiS.Q. (2013) Chemical constituents from the rhizomes of Smilax glabra and their antimicrobial activity. Molecules, 18, 5265–5287.
13.
Ur-RahmanA., ChoudharyM.I., HayatS., KhanA.M., AhmedA. (2001) Two new aurones from marine brown alga Spatoglossum variabile. Chemical and Pharmaceutical Bulletin, 49, 105–107.
14.
BeneyC., MariotteA.M., BoumendjelA. (2001) An efficient synthesis of 4,6- dimethoxyaurones. Heterocycles, 55, 967–972.
15.
HastingsJ.S., HellerH.G. (1972) The stereochemistry of aurones [2-substituted benzylidenebenzofuran-3(2H)-ones]. Journal of the Chemical Society, Perkin Transactions1, 2128–2132.
