Synthesis of Δ20-Ginsenosides Rh4, (20E)-Rh3, Rg6, and Rk1: A General Approach To Access Dehydrated Ginsenosides

Abstract

Four representative Δ²⁰-ginsenosides, namely, ginsenosides Rh₄ (1), (20E)-Rh₃ (2), Rg₆ (3), and Rk₁ (4) from Panax Ginseng, were chemically synthesized for the first time. Dehydration of the naturally occurring 20(S)-protopanaxatriol and 20(S)-protopanaxadiol provided all types of Δ²⁰-sapogenins, which were separated due to a judicious choice of protecting groups. The Δ²⁰-sapogenins were then directly glycosylated with glycosyl ortho-alkynylbenzoate donors under the catalysis of Ph₃PAuNTf₂ as key steps. The neutral conditions of the glycosylations were crucial to prevent the acid-labile Δ^20,21 double bond from isomerization.