Synthesis of crescent shaped heterocycle-fused aromatics via Garratt-Braverman cyclization and their DNA-binding studies

Three crescent shaped heterocycle-fused phenanthrene based systems 1-3 have been synthesized starting from benzene (or substituted benzene) 1,2-bis-propargyl alcohols. Bis-alkylation with propargylic bromides provided the key intermediate, the bis-propargyl bis-ethers. In spite of the possibility of many competing reactions, the latter underwent facile double Garratt-Braverman cyclization to provide compounds 1-3 in near quantitative yield, in a striking reaction involving the formation of four C-C bonds in a single step. Compounds 1-3 showed binding interaction with DNA, predominantly, via groove binding along with partial intercalation (combilexins). Molecular docking study supported the proposed binding modes. (C) 2017 Elsevier Ltd. All rights reserved.