Total Synthesis of Valerenic Acid, a Potent GABAA Receptor Modulator

Ramharter, Juergen; Mulzer, Johann.   

Organic Letters  (2009),  11(5),  1151-1153.

The first total synthesis of the sesquiterpenoid valerenic acid, a constituent of Valeriana officinalis, is described. The compound is a potent modulator of the GABAA receptor and may thus be useful in the treatment of various dysfunctions of the central nervous system. The synthesis is enantio-, diastereo-, and regiocontrolled and utilizes an enyne-RCM, a metal-coordinated Diels−Alder reaction, a hydroxy-directed Crabtree hydrogenation, and a Negishi methylation as key steps.