Abstract
The Fischer reaction of 3,11-dioxo derivatives of fusidic acid and its esters with phenylhydrazine chemoselectively occurred at the 3-position with the formation of indole-fused fusidane triterpenoids. The reaction with 3-chlorophenylhydrazine under similar conditions afforded mixtures of isomeric 6- and 4-chloro derivatives at a ratio of 3:2. 2,4-Dinitrophenylhydrazine reacted with the same fusidane diketones to give the corresponding hydrazones at the 3-oxo group. Biological screening of the synthesized compounds revealed derivatives exhibiting a high antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimum inhibitory concentration of ≤0.25 μg/mL.
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REFERENCES
Sundberg, R.J., Indoles, London: Academic, 1996. https://doi.org/10.1016/B978-0-12-676945-6.X5019-4
Austin, J.F. and MacMillan, D.W.C., J. Am. Chem. Soc., 2002, vol. 124, p. 1172. https://doi.org/10.1021/ja017255c
Wan, Y.C., Li, Y.H., Yan, C.X., Yan, M., and Tang, Z.L., Eur. J. Med. Chem., 2019, vol. 183, article ID 111691. https://doi.org/10.1016/j.ejmech.2019.111691
Wang, Q., Arnst, K.E., Wang, Y., Kumar, G., Ma, D., White, S.W., Miller, D.D., Li, W., and Li, W., J. Med. Chem., 2019, vol. 62, p. 6734. https://doi.org/10.1021/acs.jmedchem.9b00706
Hansen, K.Ø., Andersen, J.H., Bayer, A., Pandey, S.K., Lorentzen, M., Jørgensen, K.B., Sydnes, M.O., Guttormsen, Y., Baumann, M., Koch, U., Klebl, B., Eickhoff, J., Haug, B.E., Isaksson, J., and Hansen, E.H., J. Med. Chem., 2019, vol. 62, p. 10167. https://doi.org/10.1021/acs.jmedchem.9b01006
Chio, C.-M., Huang, Y.-C., Chou, Y.-C., Hsu, F.-C., Lai, Y.-B., and Yu, C.-S., ACS Med. Chem. Lett., 2020, vol. 11, p. 589. https://doi.org/10.1021/acsmedchemlett.0c00064
Zidar, N., Secci, D., Tomasič, T., Mašič, L.P., Kikelj, D., Passarella, D., Argaez, A.N., Hyeraci, M., and Via, L.D., ACS Med. Chem. Lett., 2020, vol. 11, p. 691. https://doi.org/10.1021/acsmedchemlett.9b00557
Chadha, N. and Silakari, O., Eur. J. Med. Chem., 2017, vol. 134, p. 159. https://doi.org/10.1016/j.ejmech.2017.04.003
Ihnen, M., zu Eulenburg, C., Kolarova, T., Qi, J.W., Manivong, K., Chalukya, M., Dering, J., Anderson, L., Ginther, C., Meuter, A., Winterhoff, B., Jones, S., Velculescu, V.E., Venkatesan, N., Rong, H.-M., Dandekar, S., Udar, N., Jänicke, F., Los, G., Slamon, D.J., and Konecny, G.E., Mol. Cancer Ther., 2013, vol. 12, p. 1002. https://doi.org/10.1158/1535-7163.MCT-12-0813
Pham, K.N., Lewis-Ballester, A., and Yeh, S.R., J. Am. Chem. Soc., 2019, vol. 141, p. 18771. https://doi.org/10.1021/jacs.9b08871
McGowan, D.C., Balemans, W., Embrechts, W., Motte, M., Keown, J.R., Buyck, C., Corbera, J., Funes, M., Moreno, L., Cooymans, L., Tahri, A., Eymard, J., Stoops, B., Strijbos, R., den Berg, J.V., Fodor, E., Grimes, J.M., Koul, A., Jonckers, T.H.M., Raboisson, P., and Guillemont, J., J. Med. Chem., 2019, vol. 62, p. 9680. https://doi.org/10.1021/acs.jmedchem.9b01091
Garai, S., Kulkarni, P.M., Schaffer, P.C., Leo, L.M., Brandt, A.L., Zagzoog, A., Black, T., Lin, X., Hurst, D.P., Janero, D.R., Abood, M.E., Zimmowitch, A., Straiker, A., Pertwee, R.G., Kelly, M., Szczesniak, A.M., Denovan-Wright, E.M., Mackie, K., Hohmann, A.G., Reggio, P.H., Laprairie, R.B., and Thakur, G.A., J. Med. Chem., 2020, vol. 63, p. 542. https://doi.org/10.1021/acs.jmedchem.9b01142
Amaradhi, R., Banik, A., Mohammed, S., Patro, V., Rojas, A., Wang, W., Motati, D.R., Dingledine, R., and Ganesh, T., J. Med. Chem., 2020, vol. 63, p. 1032. https://doi.org/10.1021/acs.jmedchem.9b01218
Baqi, Y., Phillaiyar, T., Abdelrahman, A., Kaufmann, O., Alshaibani, S., Rafehi, M., Ghasimi, S., Akari, R., Ritter, K., Simon, K., Spinrath, A., Kostenis, E., Zhao, Q., Köse, M., Namasivayam, V., and Müller, C.E., J. Med. Chem., 2018, vol. 61, p. 8136. https://doi.org/10.1021/acs.jmedchem.7b01768
Baird-Lambert, J., Davis, P.A., and Taylor, K.M., Clin. Exp. Pharmacol. Physiol., 1982, vol. 9, p. 203. https://doi.org/10.1111/j.1440-1681.1982.tb00798.x
Group, P.C., Lancet, 2001, vol. 358, p. 1033. https://doi.org/10.1016/S0140-6736(01)06178-5
Zhou, L.M., Kong, F.D., Fan, P., Ma, Q.Y., Xie, Q.Y., Li, J.H., Zheng, H.Z., Zheng, Z.H., Yuan, J.Z., Dai, H.F., Luo, Q.Q., and Zhao, Y.X., J. Nat. Prod., 2019, vol. 82, p. 2638. https://doi.org/10.1021/acs.jnatprod.9b00620
Findlay, A., Foot, J.S., Buson, A., Deodhar, M., Jarnicki, A.G., Hansbro, P.M., Liu, G., Schilter, H., Turner, C.I., Zhou, W., and Jarolimek, W., J. Med. Chem., 2019, vol. 62, p. 9874. https://doi.org/10.1021/acs.jmedchem.9b01283
Norwood, V.M. IV, Brice-Tutt, A.C., Eans, S.O., Stacy, H.M., Shi, G., Ratnayake, R., Rocca, J.R., Abboud, K.A., Li, C., Luesch, H., McLaughlin, J.P., and Huigens, R.W. III, J. Med. Chem., 2020, vol. 63, p. 5119. https://doi.org/10.1021/acs.jmedchem.9b01924
Allen, G.R., Jr., Pidacks, C., and Weiss, M.J., J. Am. Chem. Soc., 1966, vol. 88, no. 11, p. 2536. https://doi.org/10.1021/ja00963a032
Garbett, N.C. and Graves, D.E., Curr. Med. Chem.: Anti-Cancer Agents, 2004, vol. 4, p. 149. https://doi.org/10.2174/1568011043482070
Gu, X.H., Wan, X.Z., and Jaing, B., Bioorg. Med. Chem. Lett., 1999, vol. 9, p. 569. https://doi.org/10.1016/S0960-894X(99)00037-2
Fischer, E. and Jourdan, F., Ber. Dtsch. Chem. Ges., 1883, vol. 16, p. 2241. https://doi.org/10.1002/cber.188301602141
Porcheddu, A., Mura, M.G., De Luca, L., Pizzetti, M., and Taddei, M., Org. Lett., 2012, vol. 14, p. 6112. https://doi.org/10.1021/ol3030956
Park, J., Kim, D.H., Das, T., and Cho, C.G., Org. Lett., 2016, vol. 18, p. 5098. https://doi.org/10.1021/acs.orglett.6b02541
Salimova, E.V., Magafurova, A.A., Tretyakova, E.V., Kukovinets, O.S., and Parfenova, L.V., Chem. Heterocycl. Compd., 2020, vol. 56, p. 800. https://doi.org/10.1007/s10593-020-02733-1
Salimova, E.V., Mamaev, A.G., Tretyakova, E.V., Kukovinets, O.S., Mavzyutov, A.R., Shvets, K.Yu., and Parfenova, L.V., Russ. J. Org. Chem., 2018, vol. 54, p. 1411. https://doi.org/10.1134/S1070428018090245
Blaskovich, M.A., Zuegg, J., Elliott, A.G., and Cooper, M.A., ACS Infect. Dis., 2015, vol. 1, p. 285. https://doi.org/10.1021/acsinfecdis.5b00044
ACKNOWLEDGMENTS
The in vitro antimicrobial activity of compounds 1–20 was evaluated according to the program of the Community for Antimicrobial Drug Discovery (CO-ADD) under financial support by the Wellcome Trust (UK) and University of Queensland (Australia). The spectral studies were carried out at the Agidel regional joint center (Ufa Federal Research Center, Russian Academy of Sciences).
Funding
This study was performed according to state assignment no. AAAA-A19-119022290012-3.
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Translated from Zhurnal Organicheskoi Khimii, 2022, Vol. 58, No. 1, pp. 36–50 https://doi.org/10.31857/S0514749222010037.
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Salimova, E.V., Parfenova, L.V. Fischer Reaction in the Synthesis of New Triterpene Indoles of the Fusidane Series. Russ J Org Chem 58, 25–37 (2022). https://doi.org/10.1134/S1070428022010031
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DOI: https://doi.org/10.1134/S1070428022010031