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

Four representative Delta(20)-ginsenosides, namely, ginsenosides Rh-4 (1), (20E)-Rh-3 (2), Rg(6) (3), and Rk(1) (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 Delta(20)-sapogenins, which were separated due to a judicious choice of protecting groups. The Delta(20)-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 Delta(20,21) double bond from isomerization.