In order to search for bioactive compounds, we have studied the chemical constituents from the organic extracts of two soft corals Sinularia granosa and Sinularia leptoclados. This study had led to the isolation of twenty-one natural compounds 1¡V21, including five new cembrane-type diterpenoids, querciformolide B (1), granosolides A¡VD (2, 3, 5, and 6) and one new secosteroid 3£],11-dihydroxy-5£],6£]-expoxy-24- methylene-9,11-secocholestan-9-one (11) along with seven know compounds from S. granosa, and two new oppositol¡Vtype sesquiterpenoids leptocladolins A and B (14 and 15), and two new steroid 24-methylenecholestan-3£],5£\,6£]-triol 11-acetate (18)¡B24(S*)-24- methylcholestan-3£],5£\,6£]-triol 11-acetate (19) along with four known compounds (16, 17, 20 and 21) from S. leptoclados. The structure of compounds 1¡V21 were established by detailed spectral data analysis (IR, MS, 1D, 2D NMR) and by comparison of the spectral data with those ofthe related known compounds. The relative stereochemistries of compounds 1, 7, 14, and 15 were further confirmed by X-ray single-crystal diffraction analysis. The absolute configurations of 1¡V3 and 14¡V17 were determined using a modified Mosher¡¦s method. The cytotoxicity of compounds 1¡V17 and 19¡V21 against the Daoy (human medulloblastoma), Hep2 (human laryngeal carcinoma), MCF-7 (human breast adenocarcinoma), Hela (human cervical epitheloid carcinoma) CCRF-CEM (human T-cell acute lymphoblastic leukemia), and DLD-1 (human colon adenocarcinoma) tumor cell lines were determined. Compounds 9, 19, and 21 showed moderate activity toward the above five tumor cells. Furthermore, compounds 11 and 17 were found to show significant activity against the accumulation of the pro-inflammatory iNOSand COX-2 protein at 10 £gM.

In order to discover and develop new drug from soft corals and gorgonian corals of Taiwan, we have searched the bioactive metabolites from the organic extracts of three soft corals Nephthea chabrolii, Sinularia manaarensis, Sinularia leptoclados, and one Gorgonian of Briareum genus. This study had led to the isolation of fifty-five natural products (1¡V55), including seventeen new meroditerpenoid-related metabolites (1¡V7 and 9¡V18), two new C18 terpenoid¡Vrelated carboxylic acids (20 and 21), three new sesquiterpenoidalnatural products (22¡V24), and two new steroids (26 and 27), along with three known compounds (8, 19, and 25) from N. chabrolii; nine new cembrane-type diterpenoids (28¡V36), along with two known cembranolides 37 and 38 from S.manaarensis; five new sesquiterpenoids (39¡V43), one steroid (47) isolated for the first time from natural sources and three known metabolites (44¡V46) from S. leptoclados; and three new briarane-type derivatives (48¡V50) and five known briarane-type compounds (51¡V55) from Briareum sp. The structures of metabolites 1¡V55, including their stereochemistries have been established by detailed spectroscopic analyses, particularly mass, 2D NMR (1H¡V1H COSY, HMQC, HMBC, and NOESY) spectroscopy and by comparison with the related physical and spectral data form other known compounds. The relative configuration of metabolite 39 was further confirmed by X-ray single-crystal analysis. Furthermore, the biosyntheses of meroditerpenoids 1, 4, 11, and 20 were proposed. To the best of our knowledge, the incorporation of a methyl group of the related meroditerpene to form a naphthoquinone as discovered herein for the first time. In above metabolites, two compounds (2 and 10) were found to exhibit significant inhibition against the growth of MCF 7, NCI-H460, and SF-268 tumor cells at 20 £gg/mL. Also, compound 2 exhibited significant cytotoxicity against the growth of MDA¡VMB¡V231cancer cell line, and moderate to weak cytotoxicity against Hep G2 and A-549 cancer cell lines and metabolite 10 exhibited moderate to weak cytotoxicity toward MDA¡VMB¡V231, Hep G2 and A-549 cancer cell lines. Furthermore, Two cembranolides (34 and 35) exhibited moderate cytotoxicity against Hepa59T/VGH, KB, Hela, and Med cell lines.

The chemical constituents of organic extracts of two Formosan soft corals Sinularia leptoclados and Sinularia nanolobata were studied. Investigation on S. leptoclados has led to the isolation of eight norditerpenes (1-8), including four new compounds, scabrolide A (1), leptolide A (2), leptolide B (3), leptolide C (4) and four know compounds (5-8), (11, 12)-epileptolide (5), ineleganolide (6), (1R*,5R*,8R*,10S*,11S*)¡V11¡Vhydroxyl¡V1¡Visopropenyl¡V8¡Vmethyl¡V3,6¡Vdioxo¡V5,8¡Vepoxycyclotetradec¡V12¡Vene¡V10,12¡Vcarbolactone (7) and (1R*,5R*,8R*,10S*,11R*)¡V11¡Vhydroxyl¡V1¡Visopropenyl¡V8¡Vmethyl¡V3,6¡Vdioxo¡V5,8¡Vepoxycyclotetradec¡V12¡Vene¡V10,12¡Vcarbolactone (8). Also, investigation on the chemical constituents of S. nanolobata has led to the isolation of two new compounds (9-10), nanolobatallin A (9) and nanolobatallin B (10). The structures of the new metabolites were determined on the basis of spectroscopic analyses, including MS, IR, 1D and 2D NMR. The cytotoxicities of the isolates against the NUGC, HONE-1, KB and Hepa59T/VGH cancer cell lines were studies. Compounds 7, 8 and 10 showed moderate cytotoxicity against KB and Hepa59T/VGH cancer cell lines. Compound 9 exhibited moderate cytotoxicity against Hepa59T/VGH cancer cells.

Soft corals of the genus Sinularia have been proved to yield a wide variety of secondary metabolites. In order to search for novel bioactive substances from marine organisms, we have investigated the secondary metabolites of the soft corals Sinularia leptoclados and Sinularia sandensis. Chromatographic separation of the organic extracts of the Formosan soft coral Sinularia leptoclados, collected at Dongsha Atoll of the South China Sea, led to the isolation of four new steroids (1-3 and 11), along with an unexpected artificial sterol (5) and six known 9,11-secosteroids (4 and 6-10). In addition, the acetone extract of the soft coral, Sinularia sandensis, collected at the Tsau-Lou-Cho Island off the southwestern coast of Taiwan, yielded three novel sesquiterpenoids (12-14). The structures of the isolated metabolites were elucidated by extensive spectroscopic analyses (IR, UV, mass, optical rotations, CD, 1D and 2D NMR) and by comparison of the spectral data with those of the related known compounds. Moreover, the absolute configuration of 12 was established by application of modified Mosher¡¦s method. The cytotoxicity against of P-388 (mouse lymphocytic leukemia), HT-29 (human colon adenocarcinoma), and A-549 (human lung epithelial carcinoma) cells of metabolites 1-4 and 6-14 as well as the anti-HCMV (human cytomegalovirus) activities of metabolites 4, 10, 11, and 13 were evaluated. Metabolites 2, 4 and 6-10 exhibited significant activity against P-388 cell in vitro (IC50¡Ø4 mg/mL).

Chromatographic purification of a methylene chloride extract of Formosan soft coral Sarcophyton crassocaule (collected in Green island) led to the isolation of two new (1S*, 3R*, 4R*, 7E, 11E, 14R*)-3, 4-epoxycembra-7, 11, 15-trien-1, 14-olide (1) and (1R*, 3E, 7E,11R*, 12S*, 14R*)-11, 12-epoxycembra-3, 7, 15-trien-1, 14-olide (2) isomeric diterpenoids , a known cyclic peroxide diterpenoid (1R*, 2S*, 3E, 7S*, 8R*, 11S*, 12Z)-8, 11-epidioxy-7-acetoxycembra-3, 12, 15-trien-1, 2-olide (3), as well as two known (24S)-24-methylcholestane-3b, 5a, 6b-triol (4) and 24x-methyl-cholestane -3b, 5a, 6b, 25-tetrol 25-monoacetate (5) steroids. Chromatographic fractionation of a methylene chloride extract of two Formosan soft corals Sarcophyton elegans (collected in Green island) led to the isolation of a known 24x-methylcholestane -3b, 5a, 6b, 25-tetrol 25-monoacetate (5) steroid, the methylene chloride extract of Sarcophyton trocheliophorum, on the other hand, afforded a known diterpenoid, (+)-isosarcophine (6). Purification of a methylene chloride extract of Octocorallia soft coral (unidentified) led to the isolation of two known steroids, cholesterol (7) and (22E, 24S)-24-methylcholesta-5, 22-dien-3b-ol (8). Compounds 1-7 exhibited cytotoxicity against P388 cancer cell line. Compounds 2 and 5 were active against HT-29 cancer cell line.

The organic extracts of two marine soft corals Pachyclavularia violacea and Subergorgia suberosa, collected along the coast of Kenting, Taiwan, were found to exhibit significant cytotoxicities toward several cancer cell lines (Table 1). In order to discover bioactive compounds, we have investigated the chemical constituents of these two marine organisms. Investigation on P. violacea has led to the isolation of twenty-five compounds, including twenty-one new compounds, pachyclavulariolide G (1), pachyclavulariolide H (3), pachyclavulariolide I (4), pachyclavulariolides J¡VS (6¡V15), pachyclavulariaenones A¡VG (16¡V22), secopachyclavulariaenone A (23), and four known compounds pachyclavulariolide (2), pachyclavulariolide E (5), pachyclavulariolide A (24) and pachyclavulariolide B (25). Also, we have investigated the chemical constituents of S. suberosa. This study led to the isolation of fifteen compounds, including six new compounds, 2b-acetoxysubergorgic acid (27), subergorgiol (31), suberosols A¡VD (34¡V37), and nine known compounds, subergorgic acid (26), 2b-hydroxysubergorgic acid (28), methyl ester of subergorgic acid (29), 2b-acetoxy methyl ester of subergorgic acid (30), buddledin D (32), buddledin C (33), 5b-pregnan-3,20-dione (38), £G1- 5b-pregnen-3,20-dione (39) and 3a-acetoxy -5b-pregnan-20-one (40). Compounds 39, 40 were isolated from natural sources for the first time. Structures of these compounds were determined on the basis of chemical method and spectroscopic evidences. Cytotoxicities of these compounds against P-388, KB, A-549 and HT-29 cancer cell lines also were described. Compound, 7, 32, 33, 36, 37 have been found to show moderate activity toward the above cancer cell lines.

The methylene chloride extracts of Formosan soft coral Sarcophyton crassocule Von. Marenzeller (collected at Green Island off Taiwan) were found to exhibit significant cytotoxicity against P-388, HT-29, and A-549 cancer lines. Chromatographic separation led to the isolation of three known cembrane diterpenoids, GN16-34 (1), GN16-35 (2), GN16-40 (3), and a new cembrane, GN16-62 (4). The methylene chloride and acetone extracts of Formosan soft coral Xenia puerto-galerae Roxas (collected at Green Island off Taiwan) were found to exhibit significant cytotoxicity against P-388 and A-549 cancer cell lines. Chromatographic separation resulted in the isolation of six new cadinane sesquiterpenes, GN44-28 (5), GN44-30 (6), GN44-44 (7), GN44-66 (8), GN44-173 (9), GN44-149 (10), and one known dicarbocyclic diterpenes with a bicyclic [4.3.1] ring system, GN44-199 (11). Compounds 3 and 4 exhibited significant cytotoxicity against P-388, HT-29, and A-549 cancer cell lines. Compounds 1 and 2 exhibited significant cytotoxicity against P-388 cancer cell lines. Compounds 5 and 7 exhibited significant cytotoxicity against A-549 cancer cell line. compound 10 exhibited significant cytotoxicity against P-388 and A-549 cancer cell lines.