Synthesis of the Octameric Ring Containing Compound Caulerpin Using a Knoevenagel Reaction Catalyzed by an Amino Acid ‐ Ionic Liquid Solvent

Abstract

A piperidine-free synthesis for the biologically active molecule Caulerpin is presented. Methyl 2-(3-formyl-1H-indol-2-yl) acetate was synthesized and condensed into eight-membered aromatic ring structure through an intermolecular Knoevenagel reaction was catalyzed using an amino acid-ionic liquids solvent, giving yield of 61 %. Furthermore, five 2,3,6-trifunc-tional indole derivatives with 6-position substituents were used to obtain 6,6'-disubstituted derivatives, with yields ranging from 23 % to 31 %. Bioactivity tests demonstrated that 6,6'difluorocaulerpin significantly inhibited the immortalized human lung cancer cell line HeLa, with the IC 50 value 9.5 μg⋅mL À 1 .[a] Z.

The Synthesis of Nitrogen- and Oxygen-Containing Heterocyclic Scaffolds Assisted by Ionic Liquids: A 2022 Literature Survey

“…123 The alkylation of 4-hydroxycoumarin (160) using secondary propargylic alcohol (161) was achieved using For the first time, Xu and co-workers reported the catalytic activity of 1-hexyl-3methyl-imidazolium chloride hexafluorophosphate [HMIM][PF 6 ] and tryptophan for the piperidine-free synthesis of caulerpin and its derivatives (166) via Knoevenagel condensation of methyl 2-(3-formyl-1H-indol-2-yl) acetate (165) in 23-31% yields (Scheme 55). 124 The yield of 166 was found to be reduced when 165 was substituted at the C-6 position on benzenoid nucleus of indole. Further, the synthesized compounds have been evaluated their potential against human lung cancer (HeLa) cell lines.…”