Synthesis of 12‐epi‐Protopanaxadiol and Formal Synthesis of Ginsenoside Chikusetsusaponin‐LT₈

Abstract

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‐LT8, isolated from Panax japonicus.