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

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-trifunctional 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 IC50 value 9.5 mu g.mL(-1).