Total synthesis of valerenic acid, a potent GABAA receptor modulator.
The first total synthesis of the sesquiterpenoid valerenic acid, a constituent of Valeriana officinalis, is described. The compound is a potent modulator of the GABA(A) 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.
Ramharter
Jürgen
J
University of Vienna, Institute of Organic Chemistry, Währinger Strasse 38, 1090 Wien, Austria.
Mulzer
Johann
J
D018757:GABA Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006865:Hydrogenation; D007192:Indenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011963:Receptors, GABA-A / Q000187:drug effects*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014632:Valerian / Q000737:chemistry
D018757:GABA Modulators; D007192:Indenes; D011963:Receptors, GABA-A; D012717:Sesquiterpenes; C037133:valerenic acid