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%.

Automated summary

A novel cascade approach for the synthesis of 5-(indol-3-yl)hydantoin framework has been developed, using indole with glyoxylic acid/pyruvic acid in a deep eutectic solution. This method was also successfully applied in the total synthesis of an alkaloid, (+/-)-oxoaplysinopsin B, with an overall yield of 48%.