3569-10-6Relevant articles and documents
From planning to optimization: Total synthesis of valerenic acid and some bioactive derivatives
Ramharter, Juergen,Mulzer, Johann
experimental part, p. 2041 - 2053 (2012/05/05)
A detailed study of the total synthesis of valerenic acid, a well known GABAA receptor subtype modulator, is described. Both successful as well as unsuccessful attempts towards the synthesis of the title compound are presented, including four different strategies to synthesize one of the key intermediates. The first two strategies are based on epoxides provided from the chiral pool, whereas the last two approaches rest on stereocontrolled modifications of 2-cyclopentenone. The streamlined synthesis implements a new one-pot reaction, which combines the addition of a Grignard species with an acid-catalyzed isomerization of the intermediate allylic alcohol. Further highlights are a stereo- and regioselective hydroxy-directed Diels-Alder reaction, a hydroxy-directed hydrogenation, and a final Negishi coupling reaction. After optimization of our synthesis, the preparation of several easily available derivatives is also discussed. Amides obtained by functionalization of the carboxyl group are more than twice as active as valerenic acid. The development and optimization of four different approaches towards valerenic acid (1) are described. The shortest approach spans 10 steps and provides valerenic acid in 25 % overall yield by incorporating a new one-pot reaction, an extremely stereo- and regioselective metal-coordinated Diels-Alder reaction, a hydroxy-directed hydrogenation, and a final Negishi coupling reaction. Copyright
Total synthesis of valerenic acid, a potent gabaa receptor modulator
Ramharter, Juergen,Mulzer, Johann
supporting information; experimental part, p. 1151 - 1153 (2009/08/07)
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
