<p> Colonies of the soft coral Sinularia polydactyla collected from the vicinity of Panjang island, Jepara region, Central Java, Indonesia were tested to examine their antibacterial properties. </p> <p> Chemical analysis and bioassay-directed purification by repetitive column chromatography using Vibrio harveyi as tester strain revealed that S. polydactyla possesses antibacterial properties against this test strain. Purification gives a mixture of esters, which inhibited the growth of the marine biofilm forming bacterium, V. harveyi with an EC50 value of 0.075 mg/10 mL of culture medium. </p> <p> Chemical synthesis of the esters Hexadecyl palmitate (1 ), hexadecyl stearate (2), octadecyl palmitate (3), and octadecyl stearate (4) was accomplished from the alcohols and fatty acid acyl halides. Each purified ester was characterized by NMR and MS. Comparison of the MS for these authentic synthetic samples with that for the biologically derived sample showed that the latter was composed predominantly of esters 1 and 3. The individual esters were tested against V. harveyi. Compound 1 was active and 4 was less active, while 2 and 3 were inactive. Hence, 1 is the major active compound against V. harveyi in the natural mixture. </p> / Thesis / Master of Science (MSc)

Marine invertebrate have been found to be a rich source of bioactive secondary metabolites. During the course of our investigation on the bioactive chemical constituents from marine invertebrates, twenty-eight metabolites have been isolated from two soft coral Lobophytum crassum and Dendronephthya griffini. Investigation on L. crassum has led to the isolation of fourteen compounds, including seven new cembranoids, crassumolides A¡VG (1¡V7), and three new glycolipids (2R)-1-hydroxy -3-hexadecyloxy-propyl-£]-D-arabinopyranoside (8), (2R)-1-hydroxy-3- octadecyloxy-propyl-£]-D-arabinopyranoside (9), and (2R)-1-acetoxy-3- hexadecyloxy-propyl-£]-D-arabino-pyranoside (10), coupled with four known compounds, lobohedleolide (11), 17-dimethylaminolobohedleolide (12), sinulariol A (13), and denticulatolide (14). Ten new steroids, griffinisterones A¡VJ (15¡V24), were isolated from the soft coral D. griffini, while a known, 15-chlorogriffinsulfate (25), and three new polychlorinated acyclic compounds¡Agriffinsulfate (26), 15-chlorogriffinol (27), and griffinol (28), were also purified from the same organism. Structures of these metabolites were identified as new natural products by extensive spectroscopic methods. Except for the use of 2D NMR, the 24-epimers of 15 and 16 were identified by a single-crystal X-ray crystallography on 15. Lobohedleolide (11), obtained in large quantity in L. crassum, has also been modified to 29¡V34 by chemical conversion. Oxidation with meta-chloro-peroxybenzoic acid (MCPBA) afforded compounds 29 and 30, and with selenium dioxide led to the formation of 31. Compound 34 is the product of O-coupling reaction of 11 with 1-hydroxybenzotriazole (HOBt). Over 99¢Mdiastereoselectivity was observed in the process of Henbest hydroxyl-directed epoxidation on 11 to yield 32. EDC-coupling with an aid of HCl salt of DMAP afforded methylester 33 in high yield, and proved the absolute stereochemistry of 3. The cytotoxicity and anti-inflammatory activities of the natural and modified compounds were also discussed herein.

This research focuses on diterpenoids from Taiwanese soft corals Xenia umbellata Lamarck, Junceella juncea Pallas and Junceella fragilis Ridley. Twelve diterpenoids in addition to one sesequiterpenoid were isolated. Our investigation of the soft coral X. umbellata Lamarck afforded five natural products, including two new xenicane diterpenes, xenibelatols A-B (1-2), together with two known xenicane diterpenes, 7,8-oxido- isoxeniolide (3), 9-hydroxyxeniolide-F (4), and a cadinene sesequiterpene, xenitorin A (5). Chemical investigation of the gorgonian J. juncea Pallas, has resulted in isolation of a new briarane diterpene, juncenolide H (6). Continuing our investigation of the gorgonian J. fragilis Ridley, we isolated seven briarane diterpenes, including four new briaranes, flajunolides A-D (7-10), along with three known briaranes, junceellolide E (11), umbraculolide A (12), 11This research focuses on diterpenoids from Taiwanese soft corals Xenia umbellata Lamarck, Junceella juncea Pallas and Junceella fragilis Ridley. Twelve diterpenoids in addition to one sesequiterpenoid were isolated. Our investigation of the soft coral X. umbellata Lamarck afforded five natural products, including two new xenicane diterpenes, xenibelatols A-B (1-2), together with two known xenicane diterpenes, 7,8-oxido- isoxeniolide (3), 9-hydroxyxeniolide-F (4), and a cadinene sesequiterpene, xenitorin A (5). Chemical investigation of the gorgonian J. juncea Pallas, has resulted in isolation of a new briarane diterpene, juncenolide H (6). Continuing our investigation of the gorgonian J. fragilis Ridley, we isolated seven briarane diterpenes, including four new briaranes, flajunolides A-D (7-10), along with three known briaranes, junceellolide E (11), umbraculolide A (12),11£\, 20£\-epoxy-4-deacetoxy junceellolide D (13). The new compounds 1,2 and 6-10 possess xenicane-type and briarane-type skeletons respectively. The structures of new compounds were determined by 1D-, 2D-NMR spectroscopic analysis and physical methods such as optical rotation, UV, IR, mass spectrum, as well as comparison with the spectroscopic data reported for related compounds. Compounds 1 and 2 are geometric isomers of compounds 3 and 4. The only difference between them resides in the side chain. The geometry of the side chain influenced the relative spatial proximity of H-12, H-13, H-14 to the carbonyl at C-3, and consequently the extent to which these protons are subjected to the anisotropic effects of the carbonyl. Compounds 6-10 have acetyl groups at C-2, C-9, C-12, C-14 positions. Because of structural difference appears in briarane skeleton, they showed different chemical shifts in specific positions. Biological activity test¡Arevealed that compound 5 exhibited moderate cytotoxic activity against KB and WiDr cancer cell lines with ED50 values at 5.9 and 9.9 £gg/ml respectively.

Global biodiversity losses are being driven by human actions, and coral reef communities are not immune. Local anthropogenic stress and global climate change are rapidly changing coral reefs, through coral bleaching and mortality. How these stressors impact the biodiversity and community structure of corals on tropical reefs will not only affect the communities of fish and invertebrates that rely on coral reefs, but they could have lasting impacts on ecosystem functioning. The record-breaking marine heatwave caused by the 2015/2016 El Niño was superimposed on a strong local human disturbance gradient on Kiritimati, Kiribati, allowing for the investigation of how these combined disturbances affect coral communities. In Chapter 2, I investigated how soft coral cover varies with these disturbances and natural environmental factors, using benthic photoquadrats collected on Kiritimati’s forereefs from 2007 to 2019. Additionally, I conducted a literature review to establish what is already known about soft coral and disturbances, to compare Kiritimati data to that found in the literature. I show that soft corals are grossly understudied, with only a fifth (19/94) of coral studies presenting any results of heat stress effects on soft corals, and even fewer (5%) presenting taxonomic-specific results. On Kiritimati, prior to the 2015/2016 El Niño, soft corals were more common at sheltered sites with lower net primary productivity, but no effect of local disturbance was found. Soft corals were, however, highly vulnerable to heat stress, with a documented complete loss after the heatwave. I also show that soft coral skeletons persisted for years after the heatwave and provided substrate for hard coral recruitment. In Chapter 3, I examined how local and global stressors affected coral diversity, using community composition photoquadrat data collected from 2013 to 2017, and developed a conceptual framework for understanding effects of multiple stressors, when there are both discrete and continuous stressors. Coral alpha diversity (assessed as Hill diversity) exhibited a non-linear relationship with local anthropogenic stress, peaking at intermediate levels, and was negatively impacted by the marine heatwave, such that sites tended to decrease in both coral richness and evenness. Coral beta diversity (assessed as community composition turnover) was significantly impacted by both stressors, but sites exposed to higher levels of anthropogenic stress tended to experience less turnover during the heatwave. Explicitly considering the relationships between the two stressors, I found that it varied depending on the intensity of anthropogenic stress and the diversity metric (i.e., richness vs. composition) examined. For Hill-Richness, I found a tipping point at moderate levels of local anthropogenic stress, below which there was an additive response and above which the response tended towards synergy. In contrast, for Hill-Shannon and Hill-Simpson the responses were additive and there was an antagonistic effect between stressors for community composition. By using the frameworks outlined in this thesis for reporting changes to soft coral due to disturbances, and examining relationships between discrete and continuous stressors, we may better predict how reefs will look in the future and what actions will conserve and assist in the recovery of coral reef ecosystems. / Graduate / 2022-08-10

Le travail présenté dans cette thèse porte sur l’isolement de métabolites secondaires de trois invertébrés marins, ainsi que sur la synthèse de molécules hybrides, notamment à visée antifouling et inhibiteurs de kinases, inspirées des motifs naturels issus des familles dispacamides et 3-alkylpyridines. Les techniques spectroscopiques et les transformations chimiques ont été largement utilisées pour les déterminations structurales. Les nouveaux composés ont été évalués biologiquement.Le travail d’isolement sur le corail mou Sinularia vanderlandi a permis de mettre en évidence trois nouveaux composés de la famille de diterpènes norcembranoïdes, dont les configurations relatives ont été déterminées. Un lien chimique a également été établi entre les nouveaux composés isolés ainsi que ceux de la même famille décrits dans la litérature.Neuf nouvelles molécules ont été obtenues de l’éponge Pipestela candelabra, quatre phopholipides et cinq composés de la famille du jaspamide, les pipestelides A-C ainsi que les 5-hydropéroxy-jasplakinolides Ca et Cb. Des travaux d’hémisynthèse ont été réalisés à partir du jaspamide pour confirmer les structures des dérivés hydropéroxydés. Cette thèse contient également une étude partielle de l’éponge Stylissa carteri qui a mis a jour deux nouvelles benzosceptrines.Les travaux de synthèses ont eu pour but d’établir les voies d’accès à des dérivés l’obtention dispacamide / 3-alkylpyridine. Trois dérivés ont ainsi été synthétisés et les évaluations biologiques sont en cours, notamment pour les activités antifouling. Des aspects structuraux de ce type de dérivés ont été abordés par la synthèse d’autres dérivés. / The work described in this thesis deals with the isolation of new metabolites from marine invertebrates in one hand, and with the synthesis of antifouling and kinase inhibitors hybrid molecules inspired from dispacamide and 3-alkylpyridine scaffolds. Spectroscopic methods and chemical modifications were used for structural determination. The new compounds were biologically evaluated.Three new compounds of the norcembranoid diterpenes were isolated from the Soft Coral Sinularia vanderlandi. The relative configurations of these metabolites were determined and a chemical link was established between these diterpenes.The investigation of the marine Sponge Pipestela candelabra has conducted to the isolation of nine new metabolites, four phospholipids and five new jaspamide congeners including pipestelides A-C and 5-hydroperoxy-jasplakinolides Ca et Cb. Hemisynthesis were conducted from the jaspamide, together with spectroscopic analysis to confirm the structures of the peroxidated compounds.Two new derivatives of benzosceptrine were isolated from a partial study of the marine Sponge Stylissa carteri.The synthesis part of this work described the access to dispacamide / 3-alkylpyridine derivatives. Three hybrids were synthetized and biological evaluation are in progress, particularly for antifouling activities. Structural aspects were also studied by the synthesis of other derivatives