A simple, efficient and atom-economic method has been developed for the synthesis of complex alkaloid-like compounds with spiro-fused indolo[2,1-b]quinazoline and cyclopropa[a]pyrrolizine or 3-azabicyclo[3.1.0]hexane moieties. We have found that one-pot, three-component 1,3-dipolar cycloaddition reactions allow the desired products to be obtained from various cyclopropene derivatives with tryptanthrin-derived azomethine ylides generated in situ, in good to high yields and excellent diastereoselectivity. The possibility of ylide generation was exemplified by using α-amino acids (l-proline, l-4-thiazolidincarboxylic acid) and simplest peptides (dipeptide Gly-Gly, tripeptide Gly-Gly-Gly). Quantum chemical investigations indicate that the reaction proceeds through the S-shaped azomethine ylide, the interaction of which with cyclopropenes proceeds via a less sterically hindered endo-transition state. The antitumor activity of some of spiro-tryptanthrin derivatives against erythroleukemia (K562), cervical carcinoma (HeLa) and colon carcinoma (CT26) cell lines was evaluated in vitro by MTS-assay.
|Publication status||Published - 2019|
Filatov, A. S., Knyazev, N. A., Shmakov, S. V., Bogdanov, A. A., Ryazantsev, M. N., Shtyrov, A. A., Starova, G. L., Molchanov, A. P., Larina, A. G., Boitsov, V. M., & Stepakov, A. V. (2019). Concise Synthesis of Tryptanthrin Spiro Analogues with In Vitro Antitumor Activity Based on One-Pot, Three-Component 1, 3-Dipolar Cycloaddition of Azomethine Ylides to Сyclopropenes. Synthesis, 51(3), 713-729.