ABSTRACT Soft corals have been proved to be a rich source of bioactive natural products. This research revealed isolation and structure elucidation of bioactive natural products in the Taiwanese soft coral Junceella juncea. The acetone extract of J. juncea collected in Ken-ting exhibited cytotoxicity against tumor cells. Bioassay- directed fractionation of the EtOAc-layer has resulted in the isolation of five new briaranes, designated juncenolides A-E (1-5) along with a known compound, junceellolide C (6). The structures of compounds 1-6 were determined by the physical methods such as mp¡BIR¡Bmass¡Band optical rotation, and 1D¡B2D NMR spectral analysis, as well as the data reported of the related compounds in publications. In addition, the relative configuration of compound 1 was further confirmed by X-ray single crystal analysis. The basic structures of compounds 1-6 contain a 6/10-membered ring linked with a £^-lactone at C-7/8 and an epoxy group at C-11/20 position. Compound 1 had a chlorine atom at C-6 position with two acetoxyl and an isobutyl groups at C-2, 9, 14 positions. Compounds 2-5 had a cis-cis conjugated double bonds system at C-3, 4, 5, 6 positions, Among them , compound 2 had four acetoxyl groups at C-2, 9, 13, 14 positions, while compounds 3 and 4 had five acetoxyl groups at C-2, 9, 12, 13, 14 positions. In particular, compound 4 had a methoxyl group at C-16 position, which was first found in the briarane-type natural products. Compound 5 had three acetyl and a 3-methylbutyl groups at C-2, 9, 13, 14 positions. In a preliminary pharmacological aporach (cytotoxicity), compound 1 exhibited moderate cytotoxicity against human colon adenocarcinoma (DLD) and oral epidermoid carcinoma (KB-16) cells at a concentration of 3.4 and 5.9 £gg/mL, respectively.

This dissertation mainly discussed the investigation of two different Formosan soft corals, Junceella juncea and Cespitularia taeniata, as well as twigs and needles of Taxus sumatrana (Taxaceae). Their EtOAc extracts were investigated by intensive chromatography. Twenty-seven new natural products were isolated and parts of their biological activities were studied. Three new briarane-type natural products, Juncenolides I-K¡]1-3¡^, were isolated from Junceella juncea. In the research of soft coral Cespitularia taeniata, eleven new compounds inculding two new skeleton natural products ¡]4-5¡^of 6/13 bicyclic, one cespitularane-type diterpene (6), four verticillane-type diterpenes (7-10), one 10, 11-seco verticillane-type diterpene (11), three sesquiterpenes (12-14) were purified. Chemical investigation of Taxus sumatrana (Taxaceae) resulted in isolation of thirteen new taxane diterpenes, including tasumatrols R-U, W, Z ¡]15-18, 20, 23¡^, six wallifoliol-type diterpenes, tasumatrols V, Y¡]19, 22¡^ and 11(15¡÷1), 11(10¡÷9) diabeotaxane diterpenes , taiwantaxins B-C ¡]25-26¡^ ; 2(3¡÷20) abeotaxane diterpene, tasumatrol X ( 21¡^; one 11(15¡÷1) abeotaxane diterpene, taiwantaxin A¡]24¡^; one 6/8/6 ring system diterpene, taiwantaxin D¡]27¡^,. All the structures of above compounds were elucidated by physical and spectroscopic analyses (IR, mass, UV, optical rotation and NMR), and also by comparisions with the published data. Cytotoxicity and in vitro anti-inflammatory activities were measured by Dr. Kuo Yao-Haur, respectively. The biological activities of compounds 1-14 against MCF-7 (Human breast adenocarcinoma), Doay (Human medulloblastoma), WiDr (Human colon adenocarcinoma), Hela (Human cervical epitheloid carcinoma) , compounds 12 and 14 showd weak cytotoxicity. Tasumatrol Y (22) exhibited mild cytotoxicity against human liver carcinoma (Hepa2) with ED50 at 3.5 £gg/mL. Taiwantaxin B (25) showed marked cytotoxicity against human prostate cancer (PC-3) cell lines with an IC50 of 5.02 +0.6 £gg/mL (8.96 +0.34 £gM).

In connection with our long-standing interest in the chemical constituents of Formosan octocorals, we have investigated the octocorals Briarium excavatum and Junceella fragilis, collected at southern Taiwan coast. During the investigation, four new metabolites brianthiens D‐G (1‐4), have been isolated from Briareum excavatum. In addition, four 11,20-epoxybriaranes including three new metabolites, fragilides B‐D (5‐7), along with a known briarane (¡V)-11£\,20£\-epoxy-4-deacetoxyjunceellolide D (8), have been obtained from J. fragilis. The structure of 8 was revised as (¡V)-11£],20£]-epoxy-4-deacetoxyjunceellolide D (8) by detailed spectral data analysis. The structures, including the relative configurations of the new briaranes 1‐7, were elucidated by spectroscopic methods. The structure of fragilide B (5) was further confirmed by X-ray diffraction analysis. The relationship between 13C NMR chemical shifts and conformation of the cyclohexane ring in briaranes possessing 11,20-epoxy group, are also described.

This dissertation mainly presented the investigation of natural products from two different Formosan gongonian soft corals, Briareum violacea and Junceella fragilis. Their extracts were examined by intensive chromatographic methods. Eighty-four compounds including fifty new briaranes were isolated, and parts of their biological activities were studied. Natural products investigation of the Taiwanese gorgonian octocoral Junceella fragilis found fifteen new briarane-type diterpenes, namely frajunolides E-S (1-15), ninteen known briaranes, eg. junceellin, junceellolides A-E¡Bjunceellolide K, 11£\,20£\-epoxy-4-deacetoxyjuncellolide D, umbraculolide A, junceellonoid A, juncin P, juncins Y-ZI, frajunolides A-D and praelolide, and a sterol, ergosterol peroxide. Soft coral B. violacea (Quoy and Gaimard) of Taiwan has isolated thirty-five new briarane-type diterpenoids, briaviolides A-Z (16-41) and viobrianolides A-I (42-50), in addition to fourteen known diterpene lactones, stylatulide lactone, excavatolide A, 9-deacetylstylatulide lactone, 4£]-acetoxy-9-deacetylstylatulide lactone¡B Brianthein Z¡B, renillafoulin A, braexcavatolide E, braexcavatolide I, minabein-4, minabein-6, milolide K, solenolide A, and solenolides D-E. Structures of all above compounds were examined by physical and spectroscopic analyses including mass, IR, UV spectra, optical rotation and 1D, 2D NMR, as well as in comparison with the published data. Moreover, the structures of compounds 16, 32 and prarlolide were further confirmed by single X-ray crystallographic analysis. The stereochemistry of these compounds was investigated by NOESY method, and the configuration of compounds 32-38 were determined by Circular Dichroism spectroscopic analysis. Cytotoixcity and in vitro anti-inflammatory activities were studied by Dr. Kuo, Yao-Haur and Dr. Hwang, Tsong-Long, respectively. Junceellin, junceellolide B and juncin ZI exhibited weak cytotoxicity against Hep2 (Human laryngeal carcinoma), Doay (Human medulloblastoma), WiDr (Human colon adenocarcinoma), Hela (Human cervical epitheloid carcinoma). The in vitro anti-inflammatory activities of 1-7 were evaluated for inhibition of elastase release and for the generation of superoxide anion, as tested on human neutrophils. Compounds 1 and 6 exhibited weak inhibition of elastase release and superoxide anion at 10 £gg/mL. The biological activity analysis of compounds 16-50 are in progress.