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The Richter reaction in the synthesis of combretastatin analogs

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Abstract

The regioselectivity of the Richter cyclization for a series of 4-halo-2-[(3,4,5 trimethoxyphenyl)ethynyl]anilines has been studied to obtain trimethoxybenzoyl-1H-indazoles, heteroanalogs of combretastatin. In aqueous acetonitrile, cinnolin-4(1H)-ones, which are products of 6-endo-dig cyclization, are formed along with 1H-indazoles, products of 5-exo-dig cyclization. In a DMSO:H2O mixture, 3-aroyl-1H-indazoles are formed exclusively. In the case of 2-[(4-methoxyphenyl)ethynyl]-4-haloanilines, the 5-exo-dig cyclization proceeds independently on the used solvent. Among the prepared trimethoxy-benzoyl-1H-indazoles, the 5-chloro-substituted indazole showed the highest cytotoxicity, while the fluoro-substituted indazole exhibited no severe cytotoxicity.

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Authors and Affiliations

  1. Institute of Chemistry, St. Petersburg State University, 26 Universitetskii prosp., Petergof, 198504, St. Petersburg, Russian Federation

    A. A. Babushkina, V. N. Mikhailov, A. D. Ogurtsova, V. N. Sorokoumov & I. A. Balova

  2. Center of Medical Chemistry, Tolyatti State University, 14 ul. Belorusskaya, 445020, Tolyatti, Russian Federation

    A. S. Bunev

Authors
  1. A. A. Babushkina
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  2. V. N. Mikhailov
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  3. A. D. Ogurtsova
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  4. A. S. Bunev
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  5. V. N. Sorokoumov
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  6. I. A. Balova
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Corresponding author

Correspondence to I. A. Balova.

Additional information

Dedicated to Academician of the Russian Academy of Sciences I. P. Beletskaya on the occasion of her anniversary.

This work was performed under financial support of the Russian Science Foundation (Project No. 21-73-00170).

No human or animal subjects were used in this research.

The authors declare no competing interests.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, Vol. 72, No. 4, pp. 1012–1022, April, 2023.

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Babushkina, A.A., Mikhailov, V.N., Ogurtsova, A.D. et al. The Richter reaction in the synthesis of combretastatin analogs. Russ Chem Bull 72, 1012–1022 (2023). https://doi.org/10.1007/s11172-023-3866-3

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