Hirsutalins I–M, eunicellin-based diterpenoids from the soft coral Cladiella hirsuta
Graphical abstract
New eunicellin-based diterpenoids, were isolated from the soft coral, Cladiella hirsuta.
Introduction
Previous reports on the chemical constituents of soft corals belonging to the genus Cladiella1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 have shown that eunicellin-based diterpenoids are major secondary metabolites in these marine organisms. During the course of our investigation into new natural substances from the soft coral Cladiella hirsuta, new eunicellin-type metabolites hirsutalins A–H,17 and several polyoxygenated steroids, hirsutosterols A–G,18 were isolated. In our continuing effort toward the discovery of new and bioactive substances from marine invertebrates, the chemical constituents of the soft coral C. hirsuta were further studied. This investigation again led to the isolation of five new eunicellin-based metabolites, hirsutalins I–M (1–5). The structures with relative configuration of compounds 1–5 were established by extensive spectroscopic analysis, including 2D NMR (1H–1H COSY, HSQC, HMBC, and NOESY) spectroscopy. The absolute configuration of 2 was further determined by Mosher's method. Cytotoxicity of metabolites 1–5 against a limited panel of human tumor cell lines including human liver carcinoma (Hep G2), human breast carcinoma (MDA-MB-231) and human lung carcinoma (A-549) and the anti-inflammatory activity of 1–5 to inhibit NO (nitric oxide) production and up-regulation of the pro-inflammatory iNOS (inducible nitric oxide synthase) in LPS (lipopolysaccharide)-stimulated RAW264.7 macrophage cells were studied.
Section snippets
Results and discussion
The frozen bodies of the octocoral C. hirsuta were minced and extracted exhaustively with acetone. The combined organic extract was concentrated to an aqueous suspension, which was partitioned between EtOAc and H2O. The EtOAc-soluble fraction was concentrated under reduced pressure and the residue was repeatedly purified by chromatography to yield metabolites 1–5 (Scheme 1).
Hirsutalin I (1) was isolated as a colorless oil. The HRESIMS of 1 exhibited an [M+Na]+ peak at m/z 505.2780, which
General experimental procedures
Optical rotation was measured on a JASCO P-1020 polarimeter. IR spectra were recorded on a JASCO FT/IR-4100 infrared spectrophotometer. ESIMS spectra were obtained with a Bruker APEX II mass spectrometer. NMR spectra were recorded on a Varian 400 MR FT-NMR at 400 MHz for 1H and 100 MHz for 13C. Silica gel (Merck, 230–400 mesh) was used for column chromatography. Precoated silica gel plates (Merck, Kieselgel 60F-254, 0.2 mm) were used for analytical TLC. High-performance liquid chromatography
Acknowledgements
Financial support awarded to J.-H.S. was provided by the National Science Council of Taiwan (NSC-100-2320-B-110-001-MY2), and the Ministry of Education of Taiwan (01C030205).
References and notes (29)
- et al.
Tetrahedron Lett.
(1977) - et al.
Tetrahedron Lett.
(1980) - et al.
Tetrahedron Lett.
(1992) - et al.
Tetrahedron Lett.
(1989) - et al.
Tetrahedron
(1993) - et al.
Steroids
(2003) - et al.
Biochem. Pharmacol.
(1999) - et al.
Phytomedicine
(2007) - et al.
J. Nat. Prod.
(2010) - et al.
Aust. J. Chem.
(2010)
Chem. Pharm. Bull.
Mar. Drugs
J. Nat. Prod.
J. Nat. Prod.
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