Abstract
Electrophilic aromatic substitution is one of the most thoroughly studied reactions in organic chemistry. In the present paper, the 5-brominated spirobrassinol methyl ethers VII, VIII were obtained by electrophilic substitution of the aromatic core of indoline at the C-5 position in the presence of various brominating agents. The same products were also prepared from 5-bromoindole (IX) following the sequence for the synthesis 1-methoxyspirobrassinol methyl ether (V) from indoline. In addition, the new related 5-bromospiroindoline derivatives XX–XXIII were synthesised and their biological activity on human tumour cell lines was examined. The presence of bromine in the indole or indoline skeleton at the C-5 position resulted in the partial increase in anticancer activity on leukaemia cell lines (Jurkat, CEM). The structures of the newly prepared products were determined by 1H and 13C NMR spectroscopy, including HSQC, HMBC, COSY, NOESY and DEPT measurements.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Acheson, R. M., Hunt, P. G., Littelwood, D. M., Murrer, B. A., & Rosenberg, H. E. (1978). The synthesis, reactions, and spectra of 1-acetoxy-, 1-hydroxy-and 1-methoxy-indoles. Journal of the Chemical Society, Perkin Transactions 1, 1978, 1117–1125. DOI: 10.1039/p19780001117.
Banerjee, T., DuHadaway, J. B., Gaspari, P., Sutanto-Ward, E., Munn, D. H., Mellor, A. L., Malachowski, W. P., Prendergast, G. C., & Muller, A. J. (2008). A key in vivo antitumor mechanism of action of natural product-based brassinins is inhibition of indoleamine 2,3-dioxygenase. Oncogene, 27, 2851–2857. DOI: 10.1038/sj.onc.1210939.
Boyd, E. M., & Sperry, J. (2011). Synthesis of the selective neuronal nitric oxide synthase (nNOS) inhibitor 5,6-dibromo-2’-demethylaplysinopsin. Synlett, 6, 826–830. DOI: 10.1055/s-0030-1259913.
Chandra, T., & Brown, K. L. (2005). Direct glycosylation: Synthesis of α-indoline ribonucleosides. Tetrahedron Letters, 46, 2071–2074. DOI: 10.1016/j.tetlet.2005.01.164.
Hanley, A. B., Parsley, K. R., Lewis, J. A., & Fenwick, G. R. (1990). Chemistry of indole glucosinolates: Intermediacy of indol-3-ylmethyl isothiocyanates in the enzymic hydrolysis of indole glucosinolates. Journal of the Chemical Society, Perkin Transactions 1, 1990, 2273–2276. DOI: 10.1039/p19900002273.
Ishiyama, H., Yoshizawa, K., & Kobayashi, J. (2012). Enantioselective total synthesis of eudistomidins G, H and I. Tetrahedron, 68, 6186–6192. DOI: 10.1016/j.tet.2012.05.071.
Kutschy, P., Dzurilla, M., Takasugi, M., Török, M., Achbergerova, I., Homzová, R., & Rácová, M. (1998). New syntheses of indole phytoalexins and related compounds. Tetrahedron, 54, 3549–3566. DOI: 10.1016/s0040-4020(98)00088-x.
Kutschy, P., Suchý, M., Monde, K., Harada, N., Marušková, R., Čurillova, Z., Dzurilla, M., Miklošová, M., Mezencev, R., & Mojžiš, J. (2002). Spirocyclization strategy toward indole phytoalexins. The first synthesis of (±)-1-methoxyspirobrassinin, (±)-1-methoxyspirobrassinol and (±)-1-methoxyspirobrassinol methyl ether. Tetrahedron Letters, 43, 9489–9492. DOI: 10.1016/s0040-4039(02)02452-8.
Kutschy, P., Salayová, A., Čurillová, Z., Kožár, T., Mezencev, R., Mojžiš, J., Pilátová, M., Balentová, E., Pazdera, P., Sabol, M., & Zburová, M. (2009). 2-(Substituted phenyl) amino analogs of 1-methoxyspirobrassinol methyl ether: Synthesis and anticancer activity. Bioorganic & Medicinal Chemistry, 17, 3698–3712. DOI: 10.1016/j.bmc.2009.03.064.
Monde, K., Taniguchi, T., Miura, N., Kutschy, P., Čurillová, Z., Pilátová, M., & Mojžiš, J. (2005). Chiral cruciferous phytoalexins: Preparation, absolute configuration and biological activity. Bioorganic & Medicinal Chemistry, 13, 5206–5212. DOI: 10.1016/j.bmc.2005.06.001.
Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65, 55–63. DOI: 10.1016/0022-1759(83)90303-4.
Pauletti, P. M., Cintra, L. S., Braguine, C. G., da Silva Filho, A. A., e Silva, M. L. A., Cunha, W. R., & Januário, A. H. (2010). Halogenated indole alkaloids from marine invertebrates. Marine Drugs, 8, 1526–1549. DOI: 10.3390/md8051526.
Pedras, M. S. C., & Zaharia, I. L. (2000). Sinalbins A and B, phytoalexins from Sinapis alba: Elicitation, isolation and synthesis. Phytochemistry, 55, 213–216. DOI: 10.1016/s0031-9422(00)00277-6.
Pedras, M. S. C., Suchý, M., & Ahiahonu, P. W. K. (2006). Unprecedented chemical structure and biomimetic synthesis of erucalexin, a phytoalexin from the wild crucifer Erucastrum gallicum. Organic & Biomolecular Chemistry, 4, 691–701. DOI: 10.1039/b515331j.
Pedras, M. S. C., Yaya, E. E., & Glawischnig, E. (2011). The phytoalexins from cultivated and wild crucifers: Chemistry and biology. Natural Product Reports, 8, 1381–1405. DOI: 10.1039/c1np00020a.
Somei, M., & Kawasaki, T. (1989). A new and simple synthesis of 1-hydroxyindole derivatives. Heterocycles, 29, 1251–1254. DOI: 10.3987/com-89-5037.
Wang, W., Xiong, C. Y., Yang, J. Q., & Hruby, V. J. (2001). Practical, asymmetric synthesis of aromatic-substituted bulky and hydrophobic tryptophan derivatives. Tetrahedron Letters, 42, 7717–7719. DOI: 10.1016/s0040-4039(01)01626-4.
Author information
Authors and Affiliations
Corresponding author
Additional information
Dr. Peter Kutschy passed away on 11 June 2012.
Rights and permissions
About this article
Cite this article
Očenášová, L., Kutschy, P., Gonda, J. et al. Synthesis of new 5-bromo derivatives of indole and spiroindole phytoalexins. Chem. Pap. 70, 635–648 (2016). https://doi.org/10.1515/chempap-2015-0230
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1515/chempap-2015-0230