A Cascade Approach for the Synthesis of 5‑(Indol-3-yl)hydantoin: An Application to the Total Synthesis of (±)-Oxoaplysinopsin B

A cascade
approach to the synthesis of 5-(indol-3-yl)­hydantoin
framework has been developed by the reaction of indole with glyoxylic
acid/pyruvic acid under a deep eutectic solution, (+)-tartaric acid-dimethylurea. N,N′-Dimethylurea from a deep eutectic
solution functions as a reactant as well as a solvent mixture. Isolation
of the intermediate, 5-hydroxyhydantoin, and its reaction with indole
provides the mechanistic evidence for this reaction. This method was
successfully applied in the first total synthesis of an alkaloid,
(±)-oxoaplysinopsin B, with an overall yield of 48%.