Marine natural products which contain a £]- carboline skeleton are widely distributed in marine invertebrates. The discovery of natural £]- carboline metabolites as potent antitumor and antival agents has stimulated a great interest on the synthetic and pharmatological studies of£]- carboline derivatives. Herein, the preparation, charactrization and biolgical evaluation of 1-substituted 1,2,3,4-tetrahydro-£]- carboline and 3,4-dihydro-£]- carboline derivatives are reported. A facile synthetic method by the application of Pictet-Sengler reaction and DDQ oxidation allowed the preparation of compounds 63-72. Compounds 63-67 were synthesized from tryptamine and N-substituted-3-carbazole carboxaldehyde via Pictet-Spengler cyclization. Subsequent oxidation of compounds 63-67 by DDQ furnished compounds 68-72. The structures of compounds 63-67 were determined by several spectroscopic methods. A series of 1-substituted-1,2,3,4-tetrahydro-£]- carboline (63-67) and 3,4-dihydro-£]- carboline derivatives (68-72) have been evaluated to possess cytotoxicity against human tumor cells including KB16, DLD and NCI cell lines. On the other hand, chromatographic separation of acetone extract of Formosan grogonian coral Isis hippuris (collected in Gree island) has led to the isolation of four marine steroids namely hippurin-1 (74), 22-epi-hippurin-1 (80), 2-deacetylhippurin-1 (82) and 2-deacetyl-22-epi-hippurin-1 (83), as well as a new compound 4-hydroxy-5-(p-hydroxy phenyl)-pentane-2, 5-dione (86). The structures of all above compounds were established on the basis of spectral analysis. Biological studies revealed that compounds 74, 80, 82, 83 exhibited potent cytotoxicity against NUGC tumor cells, but compound 86 was inactive.

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.

Several terpenoids isolated from a Formosan gorgonian coral Isis hippuris have shown significant cytotoxic activity against various cancer cell lines. In our studies, the EtOAc and n-Hexane extracts showed potent cytotoxic response toward P-388, A549 and HT-29 cancer cell lines. In order to search other active components, we have studied the chemical constituents of I. hippuris from a Green Island specimen. Thus, the investigation on the chemical content of this extract was carried out. After our hard working, we haved isolated eleven new steroids (1- 11) , A-nor-2-carboxy-22-epi-hippurin-1 (1)¡B2a-acetoxy-3a-hydroxy- 11b-hydroxy-24-methyl-22,25-epoxy-5a-furostan-18,20b-lactone (2)¡B2a,3a-dihydroxy-11b-hydroxy-24-methyl-22,25-epoxy-5a-furostan-18,20b-lactone (3)¡B2a-hydroxy-3a-acetoxy-11b-hydroxy-24-methyl-22, 25-epoxy-5a-furostan-18,20b-lactone (4)¡B2a-hydroxy-3a-acetoxy-24- methyl-11b,18;18,20b;22,25-triepoxy-5a-furostane (5)¡B2a-acetoxy- 3a-hydroxy-24-methyl-11b,18;18,20b;22,25-triepoxy-5a-furostane (6)¡Bhippuristerone K (7)¡Bhippuristerone L (8)¡B hippuristerol F (9)¡B1a, 3b,5b,11a-tetrahydroxy gorgostan-6-one (10)¡B22-epi-hippuristan-11-one (11). We also isolated two known compounds, 22-epi- hippuristanol (19)¡B 2-desacetyl-22-epi-hippurin-1 (25). The structures of new compounds (1-11) were elucidated by spectroscopic evidences (IR, MS, 1D NMR, 2D NMR) and the comparison of literature. Among those, the stereochemistry of compound 1, with a new skeleton, were confirmed by single-crystal X-ray diffraction analyses. Unfortunately, because of the poor yield, the cytotoxicity test can not be carry out. But now, we try to get enough by semisynthesis.

Previous studies on the secondary metabolites of Formosan octocoral Isis hippuris were collected only at Green Island. In the course of our studies on secondary metabolites from marine organisms, the acetone-solubles of the Formosan octocoral Isis hippuris collected at Orchid Island has led to the isolation of eleven polyoxygenated steroids (1¡V11), along with two known compounds (12 and 13). The structures of these compounds were determined on the basis of their spectroscopic and physical data, including NMR, IR, MS, etc. The cytotoxicity against of A-549 (human lung epithelial carcinoma), HT-29 (human colon adenocarcinoma), and P-388 (mouse lymphocytic leukemia) cells, and anti-HCMV (human cytomegalovirus) activity of metabolites 1¡V13 were evaluated. Compounds 12 and 13 displayed cytotoxicity against P-388 cell line with ED50 values of 3.2 and 3.6 £gg/mL, respectively. Compound 12 exhibited cytotoxicity against A-549 cell line with an ED50 value of 3.8 £gg/mL. Compound 8 exhibit inhibitory activity against HCMV, with EC50 values of 2.0 £gg/mL.

Abstract In our continuing studies on the chemical constituents of Taiwanese octocorals, the gorgonian coral Isis hippuris and the sea pen coral Virgularia juncea, which were collected from the coast of Green Island and Peng-Hung Islands, respectively, have been the subjects of our investigations. Six compounds, including two new steroids, hippuristerones A and E (1 and 2), along with three known steroids 3£]-hydroxy-5£\-pregnan -20-one (3), prenga-4-ene-3,20-dione (4), prenga-1,4-diene-3,20-dione (5) and a known sesquiterpene subergorgic acid (6) were isolated from I. hippuris. Four compounds, incoulding a new sesquterpene, junceol A (7) and two known diterpenoids, sclerophytin A (8), cladiellisin (9) and a known steroid 24-methylenecholesterol (10) were isolated from V. juncea. The structures of above isolates were determined by physical (mp and optical rotation) and extensive spectral (UV, IR, MS, HRMS, 1D and 2D NMR) analysis and by comparison with the related physical and spectral data from other known compounds. The structure, including the relative configuration of hippuristerone A (1) was further confirmed by a single-crystal X-ray analysis.Furthermore, the relative configuration of hippuristerone E (2) was supported by the chemical dynamics calculations.

Abstract Several sesquiterpenes isolated from a Formosan gorgonian coral Isis hippuris have shown significant cytotoxic activity against various cancer cell lines. In order to search other active components, we have investigated the chemical constituent of I. hippuris from a Green Island specimen. In the cytotoxcity assay, the EtOAc extract showed potent cytotoxic response toward P-388, A549 and HT-29 cancer cell lines. Thus, the investigation on the chemical content of this extract was carried out. This study finally led to the isolation of twelve steroids(1-12). Nine metabolites, hippuristerone G (1)¡Bhippuristerone H (2), hippuristerone I (3)¡Bhippuristerone J (4)¡Bhippuristerol E (5)¡B2a,3a-diacetoxy-24-methyl- 11b,18; 18,20b; 22,25-triepoxy-5a-furostane (7)¡B2a,3a-diacetoxy-11b- hydroxy-24-methyl-22,25-epoxy-5a-furostan-18,20b-lactone (10)¡B3a- acetoxy-11b,18a-dihydroxy-24-methyl-18,20b; 22,25-diepoxy-5a- furostane (11) and 2a,3a-diacetoxy-11b,18a-dihydroxy-24-methyl-18, 20b; 22,25-diepoxy-5a-furostane (12) are new compounds, whereas hippuristerone A (6), 3a-acetoxy-24-methyl-11b,18; 18,20b; 22,25- triepoxy-5a-furostane (7) and 3a-acetoxy-11b-hydroxy-24-methyl-22,25- epoxy-5a-furostan-18,20b-lactone (9) are known compounds. The structures of 1-12 were elucidated by spectroscopic evidences (IR, MS, 1D NMR, 2D NMR) and chemical method. The stereochemistries of compounds 7 and 9 were further confirmed by single-crystal X-ray diffraction analyses. Cytotoxicity test revealed that hippuristerone I (3) exhibited moderate inhibition toward NCI cancer cell line.

Abstract The n-hexane extract of Formosan gorgonian coral Isis hippuris (Isididae) collected from Green Island was found to exhibit significant cytotoxicity against P-388, A-549 and HT-29 cell lines. Cytotocicity-guided fractionation of this extract led to isolation of a known subersenone (1), five new suberosanane analogues, suberosanone (2), suberosenol A (3), suberosenol B (4), suberosenal A acetate (5) and suberosenol B acetate (6), two sesquiterpenes of novel skeletons, isishippuric acid A (7) and B (8). Three known compounds, subergorgic acid (9). 3-hexadecyl-5-hydroxy- 5-methyl-5-hydrofuran-2-one (10) and prenga-1,4-diene-3,20-dione (11) were also isolated along with the novel compound. Compounds 2-6 and 8 showed potent cytotoxicities against P-388, A-549 and HT-29 cells.