A novel cytotoxic diterpenoid, chabrolin A (1) (possessing an unprecedented terpenoid skeleton), as well as three new cytotoxic sesquiterpenoids, parathyrsoidins E–G (2–4), were isolated by cytotoxicity-guided fractionation from soft corals Nephthea chabroli and Paralemnalia thyrsoides. The structures of the new compounds were determined by extensive analysis of spectroscopic data.
Soft corals belonging to the genera Nephthea and Paralemnalia have proven to be a rich source of bioactive terpenoids. In searching for bioactive compounds from marine organisms, the crude extracts of soft corals Nephthea chabroli and Paralemnalia thyrsoides have been found to exhibit cytotoxicity against murine lymphcytic leukemis cell line, with IC50 values of 12.0 and 15.2 μg/mL, respectively.
Soft corals N. chabroli and P. thyrsoides
Cytotocixity-guided fractionation of soft corals N. chabroli and P. thyrsoides led to the isolation and characterization of a novel cytotoxic diterpenoid, chabrolin A (1) (possessing an unprecedented terpenoid skeleton), as well as three new cytotoxic sesquiterpenoids, parathyrsoidins E–G (2–4). The structures of these metabolites were established by extensive spectroscopic analysis.
Cytotoxicity-guided fractionation of the ethyl acetate extract of the soft corals N. chablroli and P. thyrsoides led to the isolation of a novel diterpenoid, chabrolin A (1) (possessing an unprecedented terpenoid skeleton) as well as three new sesquiterpenoids.
Compounds 1–4 displayed cytotoxicity against P-388, with ED50 values of 3.18, 2.59, 3.31, and 2.49 μg/mL, respectively. However, Compounds 1–4 were not cytotoxic to A549 and HT-29 cell lines and did not show anti-HCMV activity.
The molecular formula of chabrolin A (1) was determined as C20H32O from its HR-FAB-MS, 13C NMR, and DEPT spectroscopic data. The 13C NMR and DEPT spectrum of 1 exhibited the presence of four methyl, seven sp3 methylene, three sp3 methine, two sp2 methine, two sp3 quaternary, and two sp2 quaternary carbons.
The presence of two trisubstituted olefins in 1 was shown by the NMR data [δH 5.59 t (J = 8.0 Hz), 5.13 t (J = 7.2 Hz); δC 144.5 C, 121.6 CH, 130.9 C, 125.3 CH]. The NMR data [δH 0.25 dd (J = 15.2, 7.2 Hz), 0.36 m, 0.49 m, 0.78 dd (J = 14.8, 7.2 Hz); δC 8.6 CH2, 15.6 CH, 23.7 CH] pointed to a 1,2-disubstituted cyclopropane ring in 1.
The 1H NMR spectrum displayed signals for four tertiary methyl groups, (δH 0.52, 0.64, 1.62, 1.69). The presence of the oxygen bearing sp3 methine (δC 74.1 CH) was shown in the 13C NMR spectrum. By interpretation of 1H-1H COSY correlations, it was possible to establish four partial structures of contiguous proton systems extending from H-1 to H-5, from H-7 to H-8, from H-10 to H-12, and from H-14 to H-16.
HMBC correlations of (a) CH3-18 to C-5, C-6, C-7, and C-16, (b) H2-19 to C-8, C-9, C-10, C-13, and C-14, (c) H-8 to C-10, (d) CH3-20 to C-12, C-13, C-14, and C-19 connected four partial structures concluding the planar structure of 1.
The above functionalities revealed that chabrolin A (1) possesses a novel diterpene tricyclic skeleton. The relative configuration of all chiral centers in 1 was deduced from a NOESY experiment.
Assuming the β-orientation of H3-18, NOESY correlations of H3-18/H-15b, H3-18/H-8, H-8/H-10, H-10/H-11b, H-11b/H-14, and H-14/H-15b suggested all to be on the β face of the molecule.
NOESY correlations of H-15a/H-16, H-16/H-19a, H-15a/H3-20, H-16/H3-20, and H2-19/H3-20 suggested H-15a, H-16, H2-19, and H3-20 were on the α face of the molecule