New Cytotoxic Xenia Diterpenoids from the Formosan Soft Coral Xenia umbellata Chang-Yih Duh,* ,† Ali Ali H. El-Gamal, †,‡ Chin-Ying Chiang, † Chih-Ju Chu, † Shang-Kwei Wang, § and Chang-Feng Dai ⊥ Department of Marine Resources, National Sun Yat-sen University, Kaohsiung, Taiwan, Department of Microbiology, Kaohsiung Medical University, Kaohsiung, Taiwan, and Institute of Oceanography, National Taiwan University, Taipei, Taiwan, Republic of China Received June 14, 2002 Seven new cytotoxic xenicane-type diterpenoids, 9-deoxyxeniloide-E (1), 9-deoxy-7,8-epoxyxeniloide-E (2), xeniolide-G (3), 9-deoxyxenialactol-C (4), xenibecin (5), xeniolide-H (6), and xenitacin (7), were isolated from the methylene chloride solubles of the Formosan soft coral Xenia umbellata. The structures were elucidated by 1D and 2D NMR spectral analysis, and their cytotoxicity against selected cancer cells was measured in vitro. Soft corals belonging to the genus Xenia (order Alcyo- nacea, family Xeniidae) have proved to be a rich sources of terpenoids and have afforded several types of bioactive diterpenoids. 1 As part of our search for bioactive substances from marine organisms, the Formosan soft coral Xenia umbellata Lamarck was studied because the CH 2 Cl 2 ex- tracts showed significant cytotoxicity to A549 (human lung adenocarcinoma), HT-29 (human colon adenocarcinoma), and P-388 (mouse lymphocytic leukemia) cell cultures as determined by standard procedures. 2,3 Bioassay-guided fractionations resulted in the isolation of seven new cyto- toxic xenicane-type diterpenoids, 9-deoxyxeniloide-E (1), 9-deoxy-7,8-epoxyxeniloide-E (2), xeniolide-G (3), 9-deoxy- xenialactol-C (4), xenibecin (5), xeniolide-H (6), and xeni- tacin (7), from X. umbellata. Results and Discussion The molecular formula of 1 was established as C 20 H 28 O 3 by HREIMS. This formula, indicating seven degree of unsaturation, was fully supported by 13 C NMR and DEPT spectral data. Subsequent analysis of 2D NMR correlation data, focusing in particular on the interpretation of COSY, HMQC, and HMBC experiments, allowed the structure of 1 to be defined as 9-deoxyxeniolide-E. The 13 C NMR spectrum of 1 showed a carbonyl carbon at δ 173.3 and six additional olefinic carbons (three quaternary, two tertiary, one secondary), which accounted for 4 degrees of unsat- uration. Hence, 1 was clearly a tricyclic diterpene. The 1 H NMR spectrum showed one methyl bearing a trisubstituted double bond [δ 1.64 (3H, br s); 5.39 (1H, dd, J ) 12.0, 4.5 Hz)], one exomethylene [δ 4.91 (1H, s); 5.03 (1H, s)], two methyl groups on an oxygenated carbon [δ 1.35 (3H, s); 1.36 (3H, s)], two geminal lactone methylene protons [δ 4.44 (1H, d, J ) 11.7 Hz); 4.84 (1H, d, J ) 11.7 Hz)], a single allylic methine proton [δ 2.92 (1H, m)], an epoxymethine [δ 2.80 (1H, t, J ) 6.3 Hz)], and a tertiary olefinic methine [δ 5.60 (1H, t, J ) 7.5 Hz)]. Using proton-detected hetero- correlation NMR methods (HMQC and HMBC (Figure 1)), all protons were correlated with their respective carbons and the structural features of 1 were clearly assigned. The relative stereochemistry of 9-deoxyxeniolide-E was estab- lished by a NOESY experiment (Figure 2) and by compari- sons of the relevant vicinal coupling constants with several xeniolides possessing identical partial structures. 4-14 The E configuration of the carbon-carbon double bond (C-4, 12) was determined by a NOESY correlation between H-3 and H-12. The trans-ring junction was assigned according to * To whom correspondence should be addressed. Tel: 886-7-525-2000, ext. 5036. Fax: 886-7-525-5020. E-mail: yihduh@mail.nsysu.edu.tw. † National Sun Yat-sen University. ‡ On leave from Faculty of Pharmacy, Mansoura University, Egypt. § Kaohsiung Medical University. ⊥ National Taiwan University. 1882 J. Nat. Prod. 2002, 65, 1882-1885 10.1021/np020268z CCC: $22.00 © 2002 American Chemical Society and American Society of Pharmacognosy Published on Web 11/01/2002