Euphylonoids A and B, Two Highly Modified Jatrophane Diterpenoids with Potent Lipid-Lowering Activity from Euphorbia hylonoma

Abstract

Euphylonoids A (1) and B (2), two highly modified jatrophane diterpenoids, were isolated from Euphorbia hylonoma. 1 represents a new 9(10→18)-abeo-8,12-cyclojatrophane skeleton containing a cage-like 3,8-dioxatricyclo[5.1.2.0 4,9 ]decane core, while 2 is a 14(13→20)-abeo-8,12cyclojatrophane featuring an unusual 17-oxatetracyclo[12.2.1.0 1,5 .0 9,13 ]heptadecane framework. Their structural elucidation was completed by spectroscopic, chemical, computational, and single-crystal X-ray diffraction means. 2 significantly inhibited early adipogenesis in 3T3-L1 adipocytes via activating AMP-activated protein kinase signaling.

Discovery of Ingenane Diterpenoids from Euphorbia hylonoma as Antiadipogenic Agents

“…Euphylonane B (2) presented the molecular formula C 34 H 46 O 8 , 32 mass units higher than that of 1, by HRESIMS ([M + Na] + m/z 605.3071, calcd 605.3085). Interpretation of 2D NMR spectra established the carbocyclic skeleton of 2 being identical with that of 1, except that the terminal double bond in 1 was replaced by an oxygenated tertiary carbon (δ C 75.4), a methyl (δ H 1.47; δ C 23.7), and an additional methoxy group (δ H 3.34; δ C 50.9) in 2, implying that 2 was a Δ 2 (19) hydromethoxylated derivative of 1. This hypothesis was corroborated by the observation of HMBC associations of H 3 -19/C-1, C-2, and C-3 and of OCH 3 /C-2 (Figure S1).…”

“…The assembly of these fragments, hydrogen-free carbons, and other functionalities was achieved by analysis of the HMBC data (Figure 1). The HMBC correlations from an exomethylene (H 2 -19) to an sp 2 methine (C-1), a quaternary olefinic carbon (C-2), and an oxymethine (C-3) linked the conjugated diene Δ 1 (10) , Δ 2 (19) to C-3 via C-2. The exchangeable proton of OH-4 (δ H 4.03) was observed to correlate with C-3, an oxymethine (C-5), and two oxygenated tertiary carbons (C-4 and C-9), suggesting the connectivity of C-3, C-5, and C-9 through an intersection (C-4).…”

“…Our prior study on E. hylonoma led to the isolation of trace amounts of two antiadipogenic jatrophane-derived diterpenoids, euphylonoids A and B. 19 As an extension of the study on discovering more antiadipogenic diterpenes and to figure out the landscape of such polycyclic diterpenoids in this plant, 21 Euphorbia diterpenoids including 13 new ones (1−13) were obtained from the remaining fractions. Euphylonanes A and B (1 and 2) are the third and fourth rearranged ingenanes with a 6/6/7/3fused ring system, respectively, 27,44 euphylonane C (3) represents a unique 9,10-epoxy tigliane, while 4−21 are typical ingenanes varying with functionalities, among which the structures of 12 and 13 were revised to their C-17 isomer, respectively.…”

“…By analyzing their SARs, euphylonane D (4) was identified as a promising antiadipogenic candidate, with a comparable EC 50 value to those of euphylonoids A and B (EC 50 = 0.60 ± 0.27, 0.36 ± 0.07, and 0.20 ± 0.03 μM, respectively). 19 Although these three polycyclic diterpenes differed in skeleton types, they all shared a methylcyclopentane unit, which is a potential antiadipogenic pharmacophore. Besides, the common acyl groups at 3-OH in 4 and euphylonoids suggested that proper lipophilicity presumably afforded the activity.…”

Hot off the Press

“…The rearranged jatrophane diterpenoid euphylonoid A 5 has been isolated from Euphorbia hylonoma . 5 A biosynthetic pathway to euphylonoid A 5 has been proposed involving a Michael addition and a ring expansion. The structure of callinteger A 6 , from Callicarpa integerrima , was confirmed by X-ray analysis.…”