Synthesis of (+)-Lithospermic Acid

Significance

(+)-Lithospermic acid was isolated in 1975 from Danshen, a herb traditionally used in the treatment of cardiovascular disorders among other medical conditions, and has recently been shown to have potent, nontoxic anti-HIV activity. The Ellman and Bergman groups completed the first total synthesis using a rhodium-catalyzed C-H activation-hydroarylation sequence (J. Am. Chem. Soc. 2005, 127, 13496). This route uses a rhodium-catalyzed C-H insertion reaction to form the dihydrofuran core, followed by a palladium-catalyzed C-H functionalization to unite the two fragments in a convergent fashion.