Studies on the constituents of Hypericum plants (43): Meroterpenes from the leaves of Hypericum chinense

Hypericum plants are recognized as a rich source of structurally interesting meroterpenes [1]. Hyperolactones A–C [2] are meroterpenes isolated from H. chinense possessing a unique 1,7-dioxaspiro[4,4]non-2-ene-4,6-dione skeleton with a s-butyl, isopropyl, and phenyl groups, respectively. Eight hyperolactone congeners have been isolated from H. chinense to date. Among others, biyouyanagin A [3] has an intriguing chemical structure consisting of a sesquiterpene (ent-zingiberene) and meroterpene (hyperolactone C) moieties, and exhibited a potent and selective anti-HIV activity. During the structure-activity relationship study for biyouyanagin A, hyperolactone C was also found to show an anti-HIV activity [4]. These results prompted us to investigate meroterpene constituents of H. Chinense in detail.

The MeOH extract of the leaves of H. chinense was partitioned with n-hexane and water. Repeated chromatographic separations of the n-hexane-soluble materials afforded eight new meroterpenes, merohyperins A–D (1–4), 4-epi-merohyperin D (5), and 4-epi-hyperolactones A–C (6–8). The structures of 1–8 were elucidated by analyses of spectroscopic data as well as comparisons of ECD spectra with those DFT calculated spectra.

Merohyperins A (1) and B (2) are new C₁₅ meroterpenes with a γ-lactone and tetrahydrofuran moieties, respectively. Merohyperin C (3) was obtained as a separable epimeric mixture, and its structure was confirmed by chemical conversion of hyperolactone A² into 3. Merohyperin D (4) has an isobutyl group at C-7 instead of the s-butyl group for hyperolactone A, while 5 was assigned as a 4-epimer of 4. 4-Epi-hyperolactones A–C (6–8) were assigned as epimers of known meroterpenes, hyperolactones A–C, respectively.

Thus, our investigation on the leaves of H. chinense showed its complex meroterpene composition.

Acknowledgements: Mr. Kazuhiko Mori, Mori Botanical Garden, Tokushima, Japan, is acknowledged for plant collection.

Keywords: Hypericum chinense, meroterpenes, hyperolactones, merohyperins.

References:

[1] Tanaka N, Kobayashi J. Prenylated acylphloroglucinols and meroterpenoids from Hypericum plants. Heterocycles 2015; 90: 23 – 40

[2] Aramaki Y, Chiba K, Tada M. Spiro-lactones, hyperolactone A-D from Hypericum chinense. Phytochemistry 1995; 38: 1419 – 1421

[3] Tanaka N, Okasaka M, Ishimaru Y, Takaishi Y, Sato M, Okamoto M, Oshikawa T, Ahmed SU, Consentino LM, Lee KH. Biyouyanagin A, an anti-HIV agent from Hypericum chinense L. var. salicifolium. Org Lett 2005; 7: 2997 – 2999

[4] Nicolaou KC, Sanchini S, Sarlah D, Lu G, Wu TR, Nomura DK, Cravatt BF, Cubitt B, de la Torre JC, Hessell AJ, Burton DR. Design, synthesis, and biological evaluation of a biyouyanagin compound library. Proc Natl Acad Sci 2011; 108: 6715 – 6720

No conflict of interest has been declared by the author(s).