The chemistry of khat. An approach to the synthesis of euonyminol

ABSTRACT An approach to the synthesis of euonyminol, the terpenoid nucleus of the cathedulins, is described. A key step in the construction of the tricyclic core is an “epoxide cascade” which creates the tetrahydrofuran of euonyminol by a sequence of acid-catalyzed epoxide openings terminated by nucleophilic attack in the A ring. A complete regime of oxygen functionality has been installed around the perimeter of the terpenoid frame with the correct configuration at ten of the eleven stereogenic carbons. However, the final reduction of a keto group gave 9-epieuonyminol rather than the natural product. In addition, syntheses of dimethyl cathate and edulindiol were completed in anticipation of their eventual coupling to euonyminol to produce cathedulin K-19, a constituent of the drug “khat”. The asymmetric synthesis of edulindiol established its absolute configuration as (S).