Synthesis of 12‐ epi ‐Protopanaxadiol and Formal Synthesis of Ginsenoside Chikusetsusaponin‐LT 8

In the context of the total synthesis of protopanaxadiol, two strategies were explored. One strategy from an optically active trienic epoxide, possessing a 5‐membered ring, prepared from ( S )‐epoxy‐limonene and ( S )‐epoxyfarnesol, which was submitted to Ti‐(III)‐mediated radical cascade to afford an original tetracyclic structure resulting from a 6‐ endo ‐ trig 6‐ endo ‐ trig 8‐ endo ‐ trig process. A second strategy, starting from a Wieland‐Miescher‐type ketone, using a “ring‐by‐ring” synthesis allowed the synthesis of 12‐ epi ‐protopanaxadiol. In this latter strategy, an efficient sequence of reactions to install the two vicinal C8–C14 quaternary centers involves: i) a Barbier type reaction; ii) an oxidative allylic transposition and iii) a nickel‐catalyzed addition of trimethylaluminium. By using this second strategy, 20‐hydroxydammar‐24‐ene‐3,12‐dione was synthesized which represents a formal synthesis of chikusetsusaponin‐LT 8 , isolated from Panax japonicus .