Spirocyclic Acylphloroglucinol Derivatives from <i>Hypericum beanii</i>

Abstract

Polyprenylated acylphloroglucinols, featured a highly oxygenated bicyclo[3.3.1]-nonane-2,4,9-trione or bicyclo[3.2.1]-octane-2,4,8-trione core decorated with C 5 H 9 or C 10 H 17 (prenyl, geranyl, etc.) side chains, were only isolated from the Guttiferae plants so far.1) This type of metabolites were reported to possess a wide variety of biological activities such as antimicrobial, antidepressant, antioxidant, cytotoxic, and anti-human immunodeficiency virus (HIV) effects. 2-7)As an important member of the family Guttiferae, the genus Hypericum have been proved to be a prolific source of this special type metabolites. [8][9][10][11] H. beanii N. Robson is a shrub of this genus and widely distributed in Guizhou and Yunnan Provinces, P. R. China. 12) Two anti-staphylococcal acylphloroglucinols have been isolated from this plant previously.13) Our phytochemical investigation on the methanol extract of this plant led to the isolation of four new acylphloroglucinols, hyperbeanols A-D (1-4), together with the known hypercalin B (5), 14) (1S,4S,5S,10R)-4,10-guaianediol (6), 15) (ϩ)-alismoxide (7), 16) guaia-6,10(14)-dien-4-ol (8), 17 calycinoxanthone D (9), 18) ugaxanthone (10), 19) 2,5-dihydroxyxanthone (11), 20) 1,3-dihydroxy-6-methoxyxanthone (12), 21) 3,6,7-trihydroxy-1-methoxyxanthone (13), 22) 1,2,5-trihydroxyxanthone (14),28) The cytotoxicity of 1-5 against the cancer cell lines SK-BR-3, HL-60, SMMC-7721, PANC-1, MCF-7, and K562 were examined. Reported herein are the isolation, structure elucidation, and cytotoxic evaluation of compounds 1-5. The MeOH extract (611 g) of the aerial parts of H. beanii (5.3 kg) was successively partitioned with petroleum ether and ethyl acetate. The petroleum ether soluble fraction (252 g) was subjected to silica gel column chromatography, Sephadex LH-20, and preparative HPLC to afford compounds 1-8. The ethyl acetate portion (167 g) was also purified by column chromatography, semipreparative, and preparative HPLC to obtain compounds 9-20.Compound 1 (d 197.3, 113.6, 193.7), one monobenzoyl group (d 197.0, 136.9, 127.8ϫ2, 128.0ϫ2, 132.2) Four new acylphloroglucinols with an unusual 6/6/5 spirocyclic skeleton, hyperbeanols A-D (1-4), were isolated from the methanol extract of Hypericum beanii along with 16 known compounds. Their structures were established on the basis of spectroscopic and X-ray diffraction analysis. Hyperbeanols A-C were three stereoisomers different only at the relative configuration of C-4 and C-13, which were distinguished by the nuclear Overhauser effect spectroscopy (NOESY) spectroscopic data in combination with the single X-ray analysis of hyperbeanol A (1). The cytotoxic activity of hyperbeanols A-D against the cancer cell lines SK-BR-3, HL-60, SMMC-7721, PANC-1, MCF-7, and K562 was also evaluated.

Hyperascyrones A–H, polyprenylated spirocyclic acylphloroglucinol derivatives from Hypericum ascyron Linn.

“…Apart from ten degrees of unsaturation occupied by three double bonds, three carbonyls, and a phenyl group, the remaining ones required a tricyclic ring system for 1. The above information suggested that 1 was a PSAP, whose NMR spectra were similar to those of hyperbeanol A (Chen et al, 2011). The 1 H-1 H COSY spectrum indicated four proton spin systems represented as bold lines (Fig.…”

“…For structural elucidation of tomoeones D and B (Hashida et al, 2008), these researchers explained that the dramatically downfield shifted signal of C-13 in tomoeone D (d C 85.5) was ascribed to a change in relative configuration of C-13 from its epimer tomoeone B (d C 72.7, D = 12.8 ppm). However, in the case of hyperbeanols A and B (C-13 epimers) (Chen et al, 2011), the difference in chemical shift of C-13 between hyperbeanols A (d C 72.3) and B (d C 68.6) was not so obvious (D = 3.7 ppm), and the structure of hyperbeanol A was unambiguously confirmed by a single crystal X-ray diffraction analysis. In another case of the PSAPs, namely harrisotones B and C, two C-13 epimers, only a small difference (D = 3.5 ppm) was observed between the chemical shift of C-13 in harrisotones B (d C 73.0) and C (d C 69.5) (Yin et al, 2009).…”

“…Its relative configuration was elucidated by careful interpretation of its NOESY spectrum (Fig. 3) and comparison of the chemical shifts and coupling constants with those of hyperbeanol B (Chen et al, 2011). NOESY correlations from H-12 to H-7a and H-14a indicated that ring B adopts a chair conformation and that the relative configuration of H-12 was a-ori- The molecular formula of hyperascyrone E (5) was assigned C 31 H 46 O 6 by HRESIMS data (m/z 515.3317, calcd for C 31 H 47 O 6 , 515.3373).…”

“…The above mentioned facts strongly suggest that the former explanation related to the chemical shift of C-13 in tomoeone D was unreasonable, and implied that the dramatically downfield chemical shift of C-13 in tomoeone D could not be arbitrarily attributed to a configuration change at C-13. An extensive literature investigation suggested that only the linkage of a hydroperoxyl group to C-13 can result in such a significant downfield chemical shift of C-13, such as with hyperbeanol D (d C 85.1) (Chen et al, 2011) 85 ppm implied an a-orientation and that at 81 ppm implied a borientation of the hydroperoxyl group. Therefore, the hydroperoxyl groups of tomoeones D and H should be a-oriented.…”

“…Besides H. ascyron Linn., PSAPs occurs only in a limited number of plants belonging to the families Hypericaceae and Simaroubaceae, including H. geminiflorum Hemsl. (Wu et al, 2008), H. beanii N. Robson (Chen et al, 2011), H. chinense L. (Abe et al, 2011), H. pyramidatum Ait. (Force et al, 2014), and Harrisonia perforata (Blanco) Merr.…”