Total syntheses of panaginsene and jujuyane

Abstract

“Panaginsene” is the one of the sesquiterpene hydrocarbon natural product, containing an angularly fused tricyclic moiety, isolated from the roots of Panax ginseng C. A. Meyer in 2005 and it belongs to the senoxydane family according to the carbon framework. Senoxydene, which had been the only natural product of senoxydane family, was proved that its structure was incorrect through the total syntheses and is still unknown. “Panaginsene”, on the other hand, would be the first senoxydane natural product if the reported structure of panaginsene is confirmed. Through a trimethylenemethane (TMM) diyl mediated tandem cycloaddition reaction a facile total synthesis of the reported structure of panaginsene was accomplished and it show the mismatch of spectroscopic data between the natural product and synthetic compound. We postulated that 11-epi-stereoisomer of the reported structure of panaginsene might be the actual panaginsene based on the plausible biosynthetic mechanism and successfully achieved the total synthesis of it using TMM diyl cycloaddition reaction with high efficiency and stereoselectivity. Through the total syntheses, we confirmed that the original structure of “panaginsene” must be revised to 11-epi-stereoisomer as the correct structure. Jujuyane is a cyclooctanoid sesquiterpene lactone natural product isolated from Stevia jujuyensis in 1992 and it has 5 stereocenters and $\alpha$ -methylene lactone around on 8-membered ring. The eight-membered ring core of jujuyane was constructed using oxidopyrylium dimerization reaction with stereo- and regioselectivity, even though the traditional strategies to eight-membered ring are often inhibited because of difficulties originated in the high degree of ring strain and transannular interactions caused by conformational effect. The first total synthesis of jujuyane was accomplished via highly functionalized eight-membered intermediate through the dimerization of oxidopyrylium ions.