Chiral phosphoric acid-catalyzed chemo and enantioselective 1,2-addition of isatin-derived β,γ-unsaturated α-ketoesters with 4-aminoindoles at the C7 position

A protocol for the highly chemo and enantioselective 1,2-addition of isatin-derived beta,gamma-unsaturated alpha-ketoesters with 4-aminoindoles at the C7 position has been described, this process was efficiently catalyzed by a SPINOL-derived chiral phosphoric acid to afford the corresponding bisindole derivatives bearing a quaternary stereogenic center in 40-90% yields with up to 97% ee. Further biological study revealed that the products showed high in vitro cytotoxicity (IC50 < 10 mu M in most cases) towards A549, HCT116, HeLa, and KSYE150 cancer cell lines.

Automated summary

This study presents a protocol for the highly selective addition reaction of isatin-derived beta,gamma-unsaturated alpha-ketoesters with 4-aminoindoles at the C7 position. The reaction, catalyzed by a SPINOL-derived chiral phosphoric acid, yields bisindole derivatives with up to 97% enantiomeric excess. Further biological testing revealed that the products have high cytotoxicity against various cancer cell lines.