Chlorahololides A and B, Two Potent and Selective Blockers of the Potassium Channel Isolated from Chloranthus holostegius

Abstract

[structure: see text] Chlorahololides A(1) and B(2), two highly complex sesquiterpenoid dimers, were isolated from Chloranthus holostegius. Their structures and absolute configurations were established by NMR spectroscopy, X-ray crystallography, and CD. Chlorahololides A (1) and B (2) exhibited potent and selective inhibition on the delayed rectifier (IK) K+ current, with an IC50 of 10.9 and 18.6 microM, respectively.

Total Syntheses of Sarcandrolide J and Shizukaol D: Lindenane Sesquiterpenoid [4+2] Dimers

“…Many molecules among these natural products exhibit intriguing bioactivities. For example, chlorahololide A ( 2 ) is a potent and selective potassium channel blocker, and shizukaol B ( 3 ) induces toxicity mediated immunosuppression against B cells, inhibits PMA‐induced homotypic aggregation of HL‐60 cells without cytotoxicity (MIC value of 34.1 n m ), inhibits TNF‐α‐induced surface expression of cell adhesion molecules, and shows anti‐HIV activity . Shizukaol D ( 4 ) can activate AMP‐activated protein kinase, increase ACC phosphorylation in HepG2 cells, and repress the growth of human liver cancer cells .…”

“…Construction of these congested dimeric molecular skeletons through an intermolecular [4+2] cycloaddition presents a considerable synthetic challenge, which is indicated by the distance as short as 2.51 between 13H and 12'C as determined by X-ray crystallography of 2 (Figure 1 a). [4] Thus we resorted to the biosynthetic pathway of these sesquiterpenoid dimers for inspiration. Formation of lindenane sesquiterpenoid dimers, such as 1, was proposed through a intermolecular [4+2] Diels-Alder reaction.…”

Atypical Lindenane-Type Sesquiterpenes from Lindera myrrha

“…These compounds also differ from 1 by the constant occurrence of a ∆ 7,11 moiety. Remarkably, a wealth of seco d-lindenanes were reported within lindenane sesquiterpenoid [4 + 2] dimers, especially from the Sarcandra species, e.g., sarcandrolides [22,26]; and various Chloranthus plant species such as shizukaol species [27][28][29], chlorahololides [30,31], spicachloranthins E and F [32], and chlorajaponilides [33], among many others. The biosynthesis of dimeric lindenane sesquiterpenes is deemed to proceed via a Diels-Alder reaction with ∆ 4,15 and ∆ 5,6 representing the diene reactive unit [34].…”

Current Applications of Suzuki–Miyaura Coupling Reaction in The Total Synthesis of Natural Products: An update

“…They showed interesting biological activities. Chlorahololide A 274 is a potent and selective potassium channel blocker, and Shizukaol B induces toxicity mediated immunosuppression against B cells, inhibits PMA‐induced homotypic aggregation of HL‐60 cell. On the other hand, Shizukaol D 275 can activate AMP‐activated protein kinase .…”