Diterpenoids from Euphorbia glomerulans with potential reversal activities against P-glycoprotein-mediated multidrug resistance

Discovery of Ingenane Diterpenoids from Euphorbia hylonoma as Antiadipogenic Agents

“…Euphylonanes E ( 5 ) and F ( 6 ) presented the identical molecular formula C 33 H 42 O 7 according to HRESIMS analyses ([M + Na] + m / z 573.2809 and 573.2851, calcd 573.2823). Their NMR spectra (Table ) were closely related to those of euphoglonane A ( 17 ), except for the existence of an additional 2,3-dimethylbutanoate group. Such a moiety was a substituent at C-3 in 5 and at C-5 in 6 , respectively, as gleaned from the downfield-shifted oxymethine signals in 5 and 6 (H-3: δ H 5.38 in 5 , 3.78 in 6 , and 4.41 in 17 ; H-5: δ H 3.73 in 5 , 5.25 in 6 , and 3.48 in 17 ) along with the correlations from the corresponding oxymethines to the corresponding ester carbonyls in the HMBC (Figure S2).…”

“…The structure of 4 was ultimately secured by alkaline hydrolysis of 4 to 20-deoxyingenol (4a) (Scheme 1), whose structure was ascertained by X-ray diffraction analysis 30 and was thereby assigned to be 3-O-(2,3-dimethylbutanoyl)-20deoxyingenol. Their NMR spectra (Table 2) were closely related to those of euphoglonane A (17), 31 except for the existence of an additional 2,3-dimethylbutanoate group. Such a moiety was a substituent at C-3 in 5 and at C-5 in 6, respectively, as gleaned from the downfield-shifted oxymethine signals in 5 and 6 (H-3: δ H 5.38 in 5, 3.78 in 6, and 4.41 in 17; H-5: δ H 3.73 in 5, 5.25 in 6, and 3.48 in 17) along with the correlations from the corresponding oxymethines to the corresponding ester carbonyls in the HMBC (Figure S2).…”

“…Euphylonane I (9) displayed the molecular formula C 34 H 36 O 8 , an oxygen atom more than that of 19 according to HRESIMS analysis ([M + Na] + m/z 595.2318, calcd 595.2302). 31 Compound 9 was spectroscopically similar to 19 (Table 3), except that the Δ 6 in 19 was replaced by two relatively upfield-shifted oxygenated carbons (δ C 63.6 and 61.9) in 9, implying that 9 was a 6,7-epoxide analogue of 19. The hypothesis was corroborated through detailed 2D NMR analysis, especially by the observation of HMBC correlations from H-7 and H 3 -20 to C-6 and from H-14 and H 3 -20 to C-7 (Figure 1).…”

“…Euphylonane G (7) 31 with the only differences being due to the absence of the 20-methyl group and the existence of a hydroxymethyl (δ H 4.23 and 4.20; δ C 67.5) in 8, which was inferred from the chemical shifts of C-6 (Δδ C +1.8 ppm) and C-7 (Δδ C +4.2 ppm) in 8 with respect to those in 19. This hypothesis was further confirmed by correlations from H 2 -20 to C-5, C-6, and C-7 observed in the HMBC spectrum (Figure S2).…”

“…Euphylonane J (10) had the molecular formula C 41 H 40 O 9 as derived from HRESIMS analysis (m/z 699.2585 [M + Na] + , calcd 699.2565). Comparison of its NMR spectroscopic data (Table 3) with those of euphoglonane B (18) revealed that one of the gem-dimethyls in 18 was replaced by a benzoyloxymethyl group in 10, 31 3) were comparable with those of 10, with the main differences being from an elimination of one of the three benzoyl groups in 10 and the upfield-shifted H-5 signal in 11 (δ H = 5.46 in 10 and 3.49 in 11), suggesting that 11 was a 5-O-debenzoylated analogue of 10. This assumption was secured by the observation of HMBC correlations (Figure S2).…”