Total Synthesis of Cafestol from ent-Kaurenoic Acid

Herein, we present the total synthesis of cafestol, a diterpene from commercially available stevioside, in 19 steps with an overall yield of 1.59 %. This synthesis provides a rapid and scalable entry to the ent-kaurene skeleton and, finally, cafestol through early dihydroxylation and late-stage furan ring construction. A key feature of this synthesis is the intro-duction of the furan ring via an oxa-Michael-Wittig annulation using a vinyl phosphonium salt on an -hydroxy ketone substrate. This paper also highlights the extraction of ent-kaurenoic acid from sunflowers and describes its synthesis toward cafestol in 14 steps.