Prenylated Phloroglucinol Derivatives from Hypericum perforatum var. angustifolium
Chika Hashida, Naonobu Tanaka, Yoshiki Kashiwada, Makoto Ogawa, Yoshihisa Takaishi
2008
Chemical and pharmaceutical bulletin
Hypericum perforatum (St. John's Wort, Clusiaceae) has been used for centuries in the treatment of burns, bruises, swelling, inflammation, and anxiety, as well as bacterial and viral infections. In addition, H. perforatum has become popular herbal medicine quickly in the world for the treatment of mood disorders, since its effectiveness in the therapy for mild to moderate depression with a smaller side effects profile than that of traditional antidepressant medications has been claimed in the
more »
... ited States. Numerous studies have proven the clinical efficacy of H. perforatum in both human and animal behavioral models of depression. 1) This medicinal herb produces various types of secondary metabolites, including flavonoids, xanthones, naphthodianthrones, and prenylated phloroglucinols. 2) Among others, hyperforin, a main component of H. perforatum being classified as phloroglucinol derivatives, is regarded as a potential leads for new medicinal agents because of its various biological activities (e.g. antibacterial, apoptotic properties, anti-tumor, anti-inflammatory, and anti-depressant). 3, 4) We have been studying the chemical constituents of various Hypericum plants for the purpose of the search for biologically active secondary metabolites. We have so far reported anti-HIV agent, biyouyanagin A 5) and xanthones 6,7) from H. chinense, and prenylated benzophenones and xanthones from H. scabrum. 8, 9) In continuing this program, we have examined the aerial parts of H. perforatum var. angustifolium. Varieties of H. perforatum with "broad" (var. perforatum) and "narrow" (var. angustifolium) sized leaves have been recognized. 10) H. perforatum var. angustifolium was reported to contain a larger quantity of hypericin, and to have a stronger antimicrobial effect than typical variety, H. perforatum var. perforatum. 11) This paper deals with the isolation and characterization of ten prenylated phloroglucinol derivatives, including two new prenylated phloroglucinols named furoadhyperforin isomers A (1) and B (2), together with five xanthones and two flavonoids from this plant material. The methanolic extracts of the air-dried aerial parts of Hypericum perforatum var. angustifolium were successively partitioned between n-hexane, EtOAc, BuOH, and H 2 O. The nhexane, the EtOAc, and the BuOH-soluble fractions were repeatedly subjected to column chromatography, respectively, to afford two new (1, 2) and 15 known (3-17) compounds. Compounds 1 and 2 showed a hydroxyl and a carbonyl absorption bands in their IR spectrum. Their molecular formu-lae were decided as the same of C 36 H 54 O 5 on the basis of the HR-MS data. The 1 H-and 13 C-NMR spectra of 1 and 2 resembled each other, which indicated the presence of a 2methylbutanoyl group, three isoprenyl groups, two carbonyl groups, one enol moiety, one oxygenated quaternary carbon, one oxygenated methine, three quaternary carbons, one methine, four methylenes, and three tertiary methyls (Table 1) . From these data, 1 and 2 were assumed to be prenylated phloroglucinol derivatives having a 2-methylbutanoyl group in each case. Furthermore, the following characteristic spectral features are coincided with those of furohyperforins 12) : d H 4.75 (1H, dd, Jϭ10.4, 8.0 Hz), 2.99 (1H, dd, Jϭ15.0, 10.4 Hz), 2.87 (1H, dd, Jϭ15.0, 8.2 Hz), 1.28 and 1.22 (each 3H, s), d C 92.3, 71.9, 27.1, 24.8, and 23.5 in 1; d H 4.82 (1H, dd, Jϭ12.0, 8.0 Hz), 2.98 (1H, dd, Jϭ14.7, 10.0 Hz), 2.96 (1H, dd, Jϭ14.7, 8.0 Hz), 1.31 and 1.20 (each 3H, s), d C 93.0, 71.5, 27.2, 26.2, and 23.0 in 2. The 13 C-NMR data of 1 was similar to those of hyperforin isomer 1 12) except for the signals of C-2, C-10 to C-14. This fact indicated that 1 had a 2-methylbutanoyl group at C-2 instead of a 2-methylpropanoyl group in furohyperforin isomer 1. In contrast, 2 was regarded as a C-28 stereoisomer of 1 due to the small difference appeared in their chemical shifts of C-28 to C-31 (Table 1 ). The relative stereochemistry of 1 was decided as the same as that of furohyperforin isomer 1 based on the marked similarity of their 13 C-NMR data. However, the C-28 configuration of furohyperforin isomer 1 was not reported previously. The relative stereochemistry of C-28 in 1 and 2 were decided by comparison of the 1 H-NMR chemical shifts with those of garsubellins D and C, respectively, prenylated phloroglucinol derivatives isolated from Garcinia subelliptica, 13) which have the same partial structure as 1 and 2. Since the chemical shifts of H-28 for 1 and 2 (d H 4.75 in 1; d H 4.82 in 2) measured in CDCl 3 were similar, the orientations of H-28 in 1 and 2 could not be compared with those of garsubellins D and C. In contrast, those measured in C 6 D 6 showed distinguishable chemical shifts (d H 4.20 in 1; d H 4.02 in 2), which were in good agreement with those of garsubellins D and C (measured in C 6 D 6 , d H 4.20 in garsubellin D; 4.01 in garsubellin C), respectively. These observations indicated that the orientations of H-28 in 1 and 2 were a and b, respectively. Consequently, the relative stereochemistries of 1 and 2 were established as shown in Fig. 1 , and they were designated furoadhyperforin isomers A and B, respectively. The structures of 3 and 4 were assigned as furohyperforin Two new prenylated phloroglucinol derivatives and 15 known compounds were isolated from the aerial parts of Hypericum perforatum var. angustifolium. Their structures were determined on the basis of spectroscopic evidence.
doi:10.1248/cpb.56.1164
pmid:18670119
fatcat:wkaycekhj5dyzbfy5ksnd5sqvu