A domino annulation approach to 3,4-diacylpyrrolo[1,2-a]pyrazines: decoration of pyrazine units

Anuradha Dagar, Yohan Seo, Wan Namkung, Ikyon Kim

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

A new one-pot, sequential three-component access to 3,4-diacylpyrrolo[1,2-a]pyrazine was achieved from the reaction of an α-haloketone, azide, andN-substituted pyrrole-2-carboxaldehyde under mild reaction conditions, through which a polysubstitution pattern on the pyrazine moiety of the scaffold was realized. The formation of multiple bonds (one C-C and two C-N) was enabled by this domino process involving thein situgeneration of α-iminoketones, intermolecular Mannich reaction, intramolecular imine formation, and aromatization. Construction of the relevant 3,4-diacylpyrazino[1,2-a]indole and further expansion of this chemical spaceviasynthetic elaboration of the resulting products were demonstrated as well. Preliminary biological screening of the synthesized derivatives against oral adenosquamous carcinoma cells (CAL-27) and triple negative human breast cancer cells (MDA-MB-231) led us to identify a potent hit compound (7o) having ∼3 times strongerin vitroanticancer activity than that of the anticancer agent, capecitabine.

Original languageEnglish
Pages (from-to)3324-3333
Number of pages10
JournalOrganic and Biomolecular Chemistry
Volume18
Issue number17
DOIs
Publication statusPublished - 2020 May 7

Bibliographical note

Funding Information:
We thank the National Research Foundation of Korea (NRF-2017R1A2A2A05069364, NRF-2018R1A6A1A03023718, NRF-2019R1I1A1A01061117, and NRF-2020R1A2C2005961) for generous financial support.

Publisher Copyright:
© The Royal Society of Chemistry 2020.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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