Synthesis, Table of Contents Synthesis 2024; 56(11): 1799-1806DOI: 10.1055/a-2259-3283 paper Access to 8-Aminoindolizine Fused with Quinone via Cu(OAc)2-Catalyzed Domino [4+2] Annulation Authors Sunhee Lee‡ Yechan Lee‡ Wan Namkung∗ Ikyon Kim∗ Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract Cu(OAc)2-catalyzed [4+2] annulation of N-substituted pyrrole-2-carbonitriles with quinones allowed access to a wide range of 8-aminoindolizines fused with quinones through a domino process involving a sequence of intermolecular Michael addition, Thorpe–Ziegler type cyclization, and aromatization. Biological evaluation of the resulting quinone-8-aminoindolizine hybrids revealed significant anticancer effects of these compounds in human hepatocellular cells (HepG2) and prostate adenocarcinoma cells (PC-3). Key words Key wordschemical space - quinone - indolizine - hybrid structure - domino reaction - diversity-oriented synthesis - atom-economy - anticancer activity Full Text References References 1a Ali I, Lone MN, Al-Othman ZA, Al-Warthan A, Sanagi MM. Curr. Drug Targets 2015; 16: 711 1b Peerzada MN, Hamel E, Bai R, Supuran CT, Azam A. Pharmacol. Ther. 2021; 225: 107860 1c Dorababu A. Eur. J. Pharmacol. 2022; 920: 174847 2a Kim M, Jung Y, Kim I. J. Org. Chem. 2013; 78: 10395 2b Dagar A, Bae GH, Lee JH, Kim I. J. Org. Chem. 2019; 84: 6916 2c Joshi DR, Seo Y, Heo Y, Park S.-h, Lee Y, Namkung W, Kim I. J. Org. Chem. 2020; 85: 10994 2d Yoon SH, Kim SJ, Kim I. J. Org. Chem. 2020; 85: 15082 2e Dagar A, Kim I. Org. Biomol. Chem. 2020; 18: 9836 2f Lee JH, Yoon SH, Nam S, Kim I. Org. Biomol. Chem. 2021; 19: 6066 2g Joshi DR, Kim I. J. Org. Chem. 2021; 86: 10235 3 Oh H, Kim H, Kim I. J. Org. Chem. 2023; 88: 11748 4a Martínez MJ. A, Benito PB. Stud. Nat. Prod. Chem. 2005; 30: 303 4b Bolton JL, Dunlap T. Chem. Res. Toxicol. 2017; 30: 13 4c Ferreira VF, de Carvalho AS, Ferreira PG, Lima CG. S, de C da Silva F. Med. Chem. 2021; 17: 1073 4d Zhang L, Zhang G, Xu S, Song Y. Eur. J. Med. Chem. 2021; 223: 113632 5a Bowie JH, Johnson AW. Tetrahedron Lett. 1967; 1449 5b Taniguchi M, Nagai K, Watanabe M, Niimura N, Suzuki K.-i, Tanaka A. J. Antibiot. 2002; 55: 30 6 Faulds D, Balfour JA, Chrisp P, Langtry HD. Drugs 1991; 41: 400 7 Joshi DR, Kim I. Tetrahedron 2024; 151: 133787 8a Ho T.-L. Tandem Organic Reactions . John Wiley & Sons; New York: 1992 8b Domino Reactions in Organic Synthesis . Tietze LF, Brasche G, Gericke KM. Wiley-VCH; Weinheim: 2006 9 Lower yields of 4l and 4m at 100 °C were observed, which seemed to be due to instability of the alkyl G moiety of the starting materials/products. 10 Ramrao KU, Ramkumar CA, Anant NA, Ramanuja AN. Synth. Commun. 1991; 21: 1129 11 Duan X, Liu N, Liu K, Song Y, Wang J, Mao X, Xu W, Yang S, Li H, Ma J. Tetrahedron Lett. 2018; 59: 4187 12 See the experimental section for details. Supplementary Material Supplementary Material Supporting Information (PDF)
