Neo-clerodane Diterpenes from the Hallucinogenic Sage Salvia divinorum

Abstract

Seven new neo-clerodane diterpenes, salvidivins A (2), B, (3), C (4), and D (5), salvinorins H (6) and I (7), and divinatorin [corrected] F (8), along with eight known neo-clerodane diterpenes, salvinorins A (1)-F, divinatorins A and B, and seven other constituents, were isolated from the hallucinogenic sage Salvia divinorum. The structures of 1-7 were elucidated on the basis of 2D NMR spectroscopic studies.

Clerodane diterpenes: sources, structures, and biological activities

“…230 Salvidivins C ( 587 ) and D ( 588 ) from Salvia divinorum are unique neo -clerodane diterpenes that possess a γ-hydroxy-α,β-unsaturated γ-lactone moiety, and are geometrical isomers at the γ-lactone moiety. 235 …”

“…It appears that 686 and 687 are important precursors of 684 (a partial agonist of the κ-opioid receptor) and 685 (the first μ-opioid antagonist with a neo -clerodane skeleton). 235 …”

“…166,167,235,263–266,273,451 (The structures of 409–410 , 659, 686, 1240 , and 1241 are specifically shown, the remaining compounds can be found in the Structure Tables in ESI†.) In a modification study of 9 , salvinorin C ( 659 ) had 250-fold lower KOR affinity compared with 9 ( K i = 1022 nM vs .…”

Blocking Deprotonation with Retention of Aromaticity in a Plant ent‐Copalyl Diphosphate Synthase Leads to Product Rearrangement

“…For example, a number of diterpenoids derived from 3 are of pharmaceutical interest, such as salvinorin A, a known hallucinogen that, along with salvinicins A and B, are potential treatments for Alzheimer’s disease, with the first two operating as κ-opioid agonists, while the latter is a μ-opioid antagonist; as well as barbatins A–C, which showed significant cytotoxic effects against several cancer lines. [16],[17] Indeed, even (−)-kolavenol itself has been shown to exhibit antitumor activity. [18] Finally, the ability of this single residue change (requiring change of only a single nucleotide) to lead to such a dramatic change in product outcome highlights the plasticity of class II diterpene cyclases, which presumably underlies the observed diversification of LRD natural products.…”

Utilizing Nature as a Source of New Probes for Opioid Pharmacology

“…Salvidivin A was isolated from S. divinorum [72]. It was identified as a KOP antagonist and is the first naturally Utilizing nature as a source of new probes for opioid pharmacology | Review occurring diterpene to display this activity [71].…”