The First Total Synthesis of Racemic Chebulic Acid

The first total synthesis of racemic chebulic acid is reported, which is the aglycon of several antioxidant ingredients of the fruit of the Terminalia chebula tree. The route started with the straightforward preparation of an indanone-based beta-oxoester from a benzaldehyde derivative (84 % over the first five steps). The side chain of the target compound was then introduced by conjugated addition of a cuprate reagent derived from dimethyl succinate, which was followed by the first key step of the synthesis: a cerium-catalyzed alpha-hydroxylation of an beta-oxoester. The second key step was the cyanide-catalyzed ring transformation of the cyclic alpha-hydroxy-beta-oxoester to a delta-lactone. Finally, chebulic acid was obtained after six-fold demethylation of three methyl ester moieties and three phenolic ether functions. The overall synthetic route consists of nine consecutive steps and was accomplished in 15 % overall yield.

Automated summary

The first total synthesis of racemic chebulic acid from the fruit of the Terminalia chebula tree has been reported. The overall synthetic route consists of nine consecutive steps and was accomplished in 15% overall yield.