Aliphatic chain-containing macrocycles as diazonamide A analogs

Aliphatic alkyl chain-containing 12–14-membered macrocycles have been designed as structural analogs of antimitotic natural product diazonamide A. Macrocycles were synthesized from 5-bromooxazole in 7 to 9 linear steps using Ru-catalyzed ring-closing metathesis as the key transformation. Heat effect of binding to α,β-tubulin tetramer (T4-RB3 complex) has been measured for the synthesized macrocycles by isothermal titration calorimetry method.

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Acknowledgement

This work was funded by ERDF (project No. 1.1.1.1/16/A/281 “Simplified Analogues of Diazonamide A as Anticancer Agents”).

We thank Prof. K. Jaudzems for assistance with NMR experiments and the ITC assay.

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Correspondence to Edgars Suna.

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Vitkovska, V., Zogota, R., Kalnins, T. et al. Aliphatic chain-containing macrocycles as diazonamide A analogs. Chem Heterocycl Comp 56, 586–602 (2020). https://doi.org/10.1007/s10593-020-02704-6

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Keywords

  • diazonamide A
  • anticancer agents
  • macrocycles
  • ring-closing metathesis