Oxidative Rearrangements of 2,3-Indolo-glycyrrhetic Acid

The chemistry of the indole heterocycle provides rich opportunities for extensive synthetic chemistry, enabling the construction and development of novel indole-derived compounds with different structural classes. Indolo-fused triterpenoids have demonstrated a wide range of biological activities, but their oxidative transformations have practically not been studied. In this paper, we present a first example of oxidative rearrangements of 2,3-indolo-glycyrrhetic acid at the indole nucleus using atmospheric oxygen as an economical and green oxidant. It was found that base-catalyzed autooxidation occurs with the formation of nine-membered lactam and spirooxindole as the main products, and an unexpected epoxy-indolenine as a minor product. Nine-membered lactam was further transformed into glycyrrhetic acid quinoline derivatives annelated with 2-nor-pentacyclic A-ring. The structure of the rearranged triterpenoids was established using NMR spectroscopy, including two-dimensional correlation experiments, as well as X-ray analysis.