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

Alexander S. Filatov, Nickolay A. Knyazev, Stanislav V. Shmakov, Alexey A Bogdanov, Mikhail N Ryazantsev, Andrey A. Shtyrov, Galina L. Starova, Alexander P. Molchanov, Anna G. Larina, Vitali M. Boitsov, Alexander V. Stepakov

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.
Original languageEnglish
Pages (from-to)713-729
Number of pages17
JournalSynthesis
Volume51
Issue number3
DOIs
StatePublished - 2019

Keywords

  • One-pot synthesis
  • Azomethine ylides
  • 1,3-Dipolar cycloaddition
  • cyclopropenes
  • tryptanthrin
  • α-amino acids
  • peptides

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this