First Total Synthesis of the Neo-Clerodane Diterpenoid Salvinorin F

Abstract

The total synthesis of the neo-clerodane diterpenoid salvinorin F was accomplished for the first time.

Total Syntheses of Clerodane Diterpenoids—A Review

“…Synthesis of (−)-salvinorin F (211). 54 salvinorin F (211), along with isomerization of the 8α-isomer 287.…”

“…Hagiwara et al synthesized salvinorin F ( 211 ) from the lactone 271 , which was employed in the previous synthesis of salvinorin A ( 206 ) (Scheme 30). 54 Treatment of the lactone 271 with SmI 2 in the presence of excess pivalic acid resulted in regioselective reduction of the double bond at C7 to give 8α- and 8β-lactone in a 3:1 diastereomeric ratio. Deprotection of the 8β-isomer 286 led to salvinorin F ( 211 ), along with isomerization of the 8α-isomer 287 .…”

Second Generation Synthesis of the Neo-Clerodane Diterpenoid Methyl Barbascoate

“…Owing to the intriguing physiological activity of clerodane diterpenoids, such as hallucinogenic salvinorins [1], synthetic studies of clerodane diterpenoids have attracted considerable attention of synthetic organic chemists [2]. As a part of our ongoing study for the total syntheses of clerodane natural products, we previously reported the total syntheses of methyl barbascoate (1) [3] and subsequently salvinorins A (2) [4] and F (3) [5] (Figure 1).…”

“…Although the stereochemistry at C-8 was unequivocally controlled in the total synthesis, the lengthy synthetic sequence needed to be improved. As part of our study for the total syntheses of clerodane natural products, we delineate herein a more concise and expedient total synthesis of methyl barbascoate (1), according to the newly developed protocol for the total synthesis of salvinorins A (2) [4b] and F (3) [5], namely double enol triflation and a subsequent palladium catalyzed double carbonylation protocol, followed by regioselective samarium diiodide conjugate reduction. The synthetic strategy is outlined in Scheme 1.…”