The chemical constituents of organic extracts of the Formosan soft corals Sinularia sp. and Sinularia lochmodes were studied. Investigation on Sinularia sp. has led to the isolation of eight compounds (1-8), including four new compounds, 1£\,3£]-dihydroxy-24S-methylcholesta-5,9-diene (1), 1£\,3£]-dihydroxy-24-methylencholesta-5-ene (2), 1£\,3£]-dihydroxy -24S-methylcholesta-5-ene (3), sinularioperoxide E (4), and four known compounds, 7-isopropenyl-1,4a-dimethyl-decahydro-naphthalen-1-ol (5), £]-dictyopterol (6), N-(4-hydroxyphenethyl)-3-methyldodecanamide (7), (Z)-N-[2-(4-hydroxyphenyl)ethyl]-3-methyldodec-2-enamide (8). Also, investigation on the chemical constituent of Sinularia lochmodes has led to the isolation of two new compounds, lochmolin A (9) and lochmolin B (10). The structures of 1¡V10 were elucidated by spectroscopic evidences (1D NMR, 2D NMR, IR, and MS). The activity of compounds 2-6 to inhibit the pro-inflammatory iNOS and COX-2 protein expression of LPS-stimulated RAW-264.7 macrophage cells have been estimated.

The chemical constituents of organic extracts of a Formosan soft coral Sinularia lochmodes (Kolonko) (collected at Ken-Ting in Taiwan) was studied and isolated twelve nature compounds (1¡V12), including seven new compounds, lochmodesolides A¡VE (1¡V5), 4,6-dibromo-(2',5'- dibromophenoxy) anisole (6), 3£],11-dihydroxy-5£],6£]-expoxy-24- methylene-9,11-secocholestan-9-one (7), and five know compounds (8¡V12),(1R*,5R*,8R*,10S*,11R*)-11-hydroxyl-1-isopropenyl-8-methyl-3,6-dioxo-5,8-epoxycyclotetradec-12-ene-10,12-carbolactone (8), (1R*, 5S*,8R*,10S*,11R*)-11-hydroxyl-1-isopropenyl-8-methyl-3,6-dioxo-5, 8-epoxycyclotetradec-12-ene-10,12-carbolactone (9), norcembrenolide 5 (10), scabrolides A (11), ineleganolide (12). The structures of 1¡V12 were elucidated by spectroscopic evidences (1D NMR, 2DNMR, IR and MS) and chemical method. The stereochemistry of compound 5 was further confirmed by single-crystal X-ray diffraction analyses. Compounds 8 and 9 showed moderate cytotoxicity against KB, Hela, Med, NCI, DLD-1 and Hepa59T/VGH cancer cell lines.

Abstract Chromatographic purification of a methinol extract of Formosan soft coral Sinularia numerosa (collected in Green Island) led to the isolation of two norcembrane norditerpenoids, (1R*,5S*,8R*,10S*,11R*)¡V11¡Vhydroxy¡V1¡Visopropenyl¡V8¡Vmethyl¡V3,6¡Vdioxo¡V5,8¡Vepoxy¡Vcyclotetradec¡V12¡Vene¡V10,12¡Ðcarbolactone (19) and (1R*,5S*,8R*,10S*,11S*)¡V11¡Vhydroxy¡V1¡Visopropenyl¡V8¡Vmethyl¡V3,6¡Vdioxo¡V5,8¡Vepoxy¡Vcyclotetradec¡V12¡Vene¡V10,12¡Ðcarbolactone (33). Purification of a chloroform extract of the Formosan plant Aglaia elliptifolia (collected in Green Island) resulted in the isolation of six compounds, 3-hydroxy-5,7¡¦,4¡¦-trimethoxyflavone (295), dehydrodorin (135), piriferine (133), foveolin B (218), cyclopenta[b]benzofuran ligan derivative (186) and a new compound (298). Compounds 295,135,133 and 218 are known compounds; compounds 186 and 298 are new compounds. In cytotoxicity assays, compounds from Sinulari numerosa, 19 and 33 exhibited significant cytotoxicities against four cancer cell lines. However, just one compound, 186 from Aglaia elliptifolia , showed significant cytotoxicity; the other compounds were not cytotoxic (ED50 ¡Ù4£gg/mL).

We have searched the bioactive metabolites from the wild-type and cultured soft corals Sinularia flexibilis. This study led to the isolation of fifteen natural products (1¡V15), including four new metabolites (1¡V4), flexibilisolide A (1), flexibilisin A (2), quercifomolide D (3) and quercifomolide B (4) along with eight known compounds (5¡V12) from the wild-type soft coral S. flexibilis, and three new metabolites (13¡V15), flexibilisolide B (13), flexibilisin B (14), flexibilisquinone (15) along with four known compounds (9¡V12) from the cultured soft coral S. flexibilis. The structures of metabolites 1¡V15, including their stereochemistries, have been established by detailed spectroscopic analyses and by comparison with the related physical and spectral data from other known compounds. The relative configuration of metabolite 4 was further confirmed by X-ray single-crystal diffraction analysis. Furthermore, the absolute configuration of 4 was determined by a modified Mosher¡¦s method. The cytotoxicity of 1¡V15 against the growth of human tumor cell lines, including cervical epitheloid (Hela), laryngeal (Hep 2), medulloblastoma (Daoy) and breast (MCF-7) carcinoma cells was studied. The results showed that only compounds 7, 9 and 11 exhibited moderate cytotoxicities against the tested cell lines. Furthermore, compounds 1, 6, 8, 9, 11¡V13 and 15 were found to significantly inhibit the accumulation of the pro-inflammatory iNOS protein in the LPS-stimulated RAW264.7 macrophage cells at 10 £gM. At the same concentrations, compounds 11 and 12 also could significantly inhibit the accumulation of the pro-inflammatory COX-2 protein.

In order to discover and develop new drug from soft corals of Taiwan, we have searched the bioactive metabolites from the organic extracts of a soft coral Sinularia querciformis. This study had led to the isolation of seventeen cembrane-type compounds (1¡V17), including ten new natural compounds (1-10), along with seven known compounds (11-17). The structures of metabolites 1¡V17, including their stereochemistries have been established by spectroscopic analyses (IR, MS, 1D, and 2D NMR) and by comparison of the related physical and spectral data with those of other known compounds. The relative configuration of compound 2 was further confirmed by X-ray single-crystal diffraction analysis. The absolute configurations of 1¡V4, 11 and 12 were determined using a modified Mosher¡¦s method for 1 and 11. In above metabolites, compounds 14 and 17 were found to exhibit inhibition against the growth of cervical epitheloid (Hela), laryngeal (Hep 2), medulloblastoma (Daoy) and breast (MCF-7) carcinoma cells. Furthermore, compounds 3¡V7 and 11¡V17 were found to significantly inhibit the accumulation of the pro¡Vinflammatory iNOS protein at 10 £gM, and compounds 3, 11, 12, 16, and 17 were also found to significantly inhibit the accumulation of the pro¡Vinflammatory COX-2 protein at 10 £gM.

To discover novel and bioactive secondary metabolites is a main mission for natural product researchers. Soft corals of the genus Sinularia were proved to yield a wide variety of secondary metabolites including sesquiterpenoids, diterpenoids and steroids. In the thesis, the chemical examinations on the organic extracts of the soft coral Sinularia capillosa (collected at Dongsha Islands) resulted in the isolation of ten secondary metabolites (1¡V10) including five new secondary metabolites (1¡V5) and five known metabolites (6¡V10). The new secondary metabolites included one new tetraprenylbenzoquinone (1), two furanobenzosesquiterpene (2, 3), one furanosesquiterpene (4), and a novel sesquiterpene (5). The known metabolites included an acid-substituted furanosesquiterpene (6), two furanobenzosesquiterpenes (7, 8), loliolide (9), and the known sesequiterpene (10). The structures of the isolated secondary metabolites were elucidated by 1H-NMR, 13C-NMR, COSY, HSQC, HMBC, NOESY, IR, UV, CD, MS, and optical rotation. The cytotoxicities against cancer cells, anti-inflammatory effects, and anti-HCMV (human cytomegalovirus) activities of these isolated metabolites were evaluated.

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.

Abstract Investigation on the chemical constituents of EtOH extract of the Formosan soft coral Sinularia grandilobata, collected off the Kenting coast, has led to the isolation of six cembrane-type diterpenoids, grandilobatins A-F (1-6), and four steroids, sinugrandisterols A-D (7-10). All metabolites 1-10 are new natural products. The structures of 1-10 were elucidated by the analysis of spectroscopic data (MS, IR, 1D and 2D NMR) and by comparison of the related spectral data with those of related metabolites in literatures. The cytotoxicity assays of compounds 1-10 against the growth of cell lines, including MDA-MB-231(human breast cancer cell), MCF 7 (human breast cancer cell), Hep G2 (human liver carcinoma), and A-549 (human lung carcinoma), were carried out. The result showed that compound 5 exhibited moderate cytotoxicity against MDA-MB-231 cells. Compounds 7 and 8 showed moderate cytotoxicity against Hep G2 and MDA-MB-231 tumor cells and exhibited weak cytotoxicity against A-549 and MCF 7 tumor cells. Compound 9 showed weak cytotoxicity against A-549 and MCF 7 tumor cells.

In our continuing study on the chemical constituents of Taiwanese soft corals, the EtOAc extracts of a gorgonian coral Isis hippuris and a alcyonarian coral Sinularia gibberosa were investigated, respectively. Seven compounds, including 3£\,11£]-dihydroxy-24-methyl-22,25epoxy-5£\- furostan-18,20£]-lactone (1), 3-acetyl-2-deacetyl-22R-hippurin-1 (2), hippuristerone F (3), hippurin-1 (4), 22-epi-hippurin-1 (5), 3-acetyl-2- desacetyl-22-epi-hippurin-1 (6) and 2-desacetyl-22-epi-hippurin-1 (7) were isolated from I. hippuris. Three metabolites, 3£],11-dihydroxy-24- methylene-9,11-secocholest-5-en-9-one (8), 3£],11-dihydroxy-24-methyl-9, 11-secocholest-5-en- 9-one (9) and 3£]-hydroxy-11-acetoxy-24-methylene-9, 11-secocholest-5-en-9-one (10) were isolated from S. gibberosa. Among them, compounds 1¡V3, are new products. All metabolites 1¡V10 are steroids. The structures of 1¡V10 were determined by physical and spectral analysis, including IR, MS, 1D NMR (1H, 13C) and 2D NMR ( 1H-1H COSY, HMQC, HMBC and NOESY ) and by comparison with the related physical and spectral data of the known compounds. The cytotoxicity of the isolates against the P-388 ( mouse lymphocytic leukemia ), A-549 ( human lung adenocarcinoma ) and HT-29 ( human colon adenocarcinoma ) cancer cell lines were studied. Compound 9 and 10 showed significant cytotoxicity against P-388 cancer cell line. Metabolites 6 and 8 showed significant cytotoxicity against P-388 and HT-29 cancer cell lines. Compound 2, 4 and 5 exhibited potent cytotoxicity against the growth of P-388, A-549 and HT-29 cancer cell lines.

This dissertation mainly investigates the constituents of one species of sponge (Ircinia formosana) and three species of soft corals¡]Sinularia flexibilis¡BCespitularia hypotentaculata and Clavularia viridis¡^. These organisms were extracted with EtOAc and analyzed them with chemical methods. Twenty three new natural products were isolated and the cytotoxicity of these copounds was tested and evaluated. Four new C22-sesterterpenoids were isolated from the sponge Ircinia formosana, and designated as irciformonins A-D (1-4). In the investigation of the soft coral Sinularia flexibilis, nine new cembranes were purified, and they were called sinuladiterpenes A-I (5-13). Six new diterpenes, cespihypotins Q-V (14-19) were obtained from the soft coral Cespitularia hypotentaculata. In addition, the soft coral Clavularia viridis afforded four new prostanoids, designated claviridic esters A-D (20-23). The structures of these metabolites including their stereochemistries have been established by detailed spectroscopic analyses, particularly 2D NMR (1H¡V1H COSY, HMQC, HMBC, and NOESY) spectroscopy and mass and by comparison with the related physical and spectral data of known compounds. Cytotoxicity of the isolated compounds was measured by Dr. Kuo Yao-Haur, Institute of Chinese Medicine. Irciformonins C (3) and D (4) from sponge Ircinia formosana showed the cytotoxicity against WiDr (Human colon adenocarcinoma) with ED50 at 6.7 and 4.9 £gg/mL, respectively. Cespihypotin T (17) was found to exhibit the inhibition against Daoy (Human medulloblastoma) and WiDr (Human colon adenocarcinoma) at ED50 9.3 and 7.5 £gg/mL. Claviridic esters A (20) and B (21) exhibited significant cytotoxicity against the growth of Hep2 (Human hepatoma) at ED50 0.19 nad 0.16 £gg/mL, respectively. Claviridic ester B (21) also showed significant cytotoxicity against Daoy (Human medulloblastoma) tumor cells at ED50 0.18 £gg/mL.