The reproductive biology of poriferans is still poorly understood. We have investigated the sexual reproductive biology of seven demosponge species, six of them from the Mediterranean (Corticium candelabrum, Crambe crambe, Raspaciona aculeata, Axinella damicornis, Chondrosia reniformis, and Petrosia ficiformis), and one from the Pacific coast of Canada (Asbestopluma occidentalis). The thesis consists of a general introduction, 7 different chapters and a general discussion.Chapter 1. It is well established that in temperate regions invertebrates restrict their reproductive cycles to the warm periods. The sexual cycle of A. damicornis, C. candelabrum, C. reniformis, and R. aculeata is very different in timing and duration, despite all of them shared habitat and thermal regime. While the gametogenesis of R. aculeata and C. reniformis underwent during summer and autumn (warm periods in the Mediterranean), the gametogenesis of C. candelabrum and A. damicornis occurred during winter. Therefore, the relationship between gametogenesis and temperature in temperate waters was not straightforward, and many different relationships appeared.Chapter 2. The oogenesis of C. candelabrum resulted in a surprising long process, with continuous production of oocytes. However, the oocyte maturation extended for 7/8 months during autumn and winter. Spermatogenesis occurred during 4 or 5 at the end of the oocyte maturation (spring and summer). Spermatozoans were primitive but possessed a true C-shaped acrosome. Chapter 3. The gametogenesis of the oviparous demosponge P. ficiformis occurred during autumn and early winter. Large oocytes and round primitive spermatozoans with proacrosomal vesicles were released to the water on December. Recently fertilised eggs were placed in Petri dishes. Since no free-swimming larva was observed, the development in this demosponge was suggested to be direct.Chapter 4. The reproduction of the carnivorous sponge A. occidentalis was studied under light and electron microscopy. It was a contemporaneous hermaphroditic sponge with clusters of oocytes and very complex spermatic cysts. The fertilisation mechanism was unusual for the phylum Porifera, and shared many similarities with the feeding mechanism of this carnivorous sponge.Chapter 5. The spermatogenesis of the common Mediterranean demosponge C. crambe was investigated by light and electron microscopy. The mature spermatozoan was a extremely modified cell, with the body bent at the level of the flagellum insertion, a true acrosome, and a striated rootlet that connected the basal body to the mitochondrion. In addition, such modifications resembled to the sperm morphology of a phoronid, in a well example of adaptive convergence. Chapter 6. The oogenesis in A. damicornis and R. aculeata was very similar, except for the duration. While it extended for 5 months in R. aculeata, A. damicornis required 7 months to complete it. The differences resided in the vitellogenesis. Yolk was almost exclusively auto-synthesized in A. damicornis from digestion of bacteria. However, in R. aculeata the process shortened because of the help of nurse cells in creation of yolk. Chapter 7. Unspawned sperm and precursors of sperm cells were phagocytosed by motile phagocytic cells in the spermatic cysts of P. ficiformis and R. aculeata. All these features observed for the first time in demosponges revealed that sponges contain many complex features and are capable of complex processes that are usually regarded to higher invertebrates and vertebrates.

Els productes naturals són de gran importància en els sistemes de prevenció i de cura de les dolences i malalties de l'ésser humà. Així, un 50% dels fàrmacs actuals estan basats en productes naturals i un 80% de la població mundial depèn, encara avui, de la medicina tradicional. El procés de desenvolupament d'un nou fàrmac a partir d'un producte natural és llarg i complex. Les millores introduïdes recentment i de forma generalitzada a cadascuna de les etapes del procés han suposat una renovació de l'interès de la indústria farmacèutica per nous compostos naturals bioactius. La síntesi química té un paper rellevant en el procés de desenvolupament d'un nou fàrmac: la síntesi química del producte bioactiu permet assegurar la identitat del compost, així com assegurar la producció a gran escala per permetre la realització dels assaigs clínics i donar resposta a les demandes del mercat farmacèutic. La introducció de la química en fase sòlida ha estat una de les millores més importants en l'àrea de la síntesi química, permetent una exploració sintètica més ràpida i eficaç. Aquest canvi ha estat rellevant en la síntesi de pèptids i oligonucleòtids i, especialment determinant, en l'obtenció de depsipèptids cíclics produïts per microorganismes i d'interessant activitat i interès com a nous fàrmacs. Així, en la present tesi s'ha treballat en el desenvolupament de noves síntesis en fase sòlida de dos depsipèptids cíclics: la sirengotoxina i la tiocoralina, amb la finalitat de contribuir en la seva aplicació terapèutica.La sirengotoxina és un lipononadepsipèptid cíclic produït per una bactèria patògena dels arbres cítrics que ha mostrat una interessant activitat contra el paràsit de la Leishmania. En aquest projecte de fàrmac s'ha dissenyat un pèptid anàleg al pèptid natural que conserva els mateixos elements estructurals i la configuració de la cadena peptídico. S'ha obtingut mitjançant una estratègia compatible amb la síntesi del producte natural. En aquesta síntesi s'ha resolt l'obtenció de l'aminoàcid no proteïnogènic així com la seva correcta inserció a la cadena.La tiocoralina és un pèptid bicíclic simètric produït per un microorganisme marí aïllat del corall tou i que presenta una potent activitat com a antitumoral. En aquest projecte s'ha desenvolupat la síntesi d'un anàleg del pèptid natural mitjançant l'aproximació en fase sòlida. En aquest cas, també s'ha resolt la síntesi de dos aminoàcids no proteïnogènics, dues N-metil cisteïnes.Finalment, s'han aïllat nous agents antitumorals d'esponges marines recol·lectades a les costes australianes amb la finalitat d'obtenir nous projectes de fàrmacs així com per ampliar els coneixements en el procés de desenvolupament d'un nou fàrmac. / "Natural Products as a source of new drugs: cyclic depsipeptides synthesis on solid-phase and isolation of antitumoral compounds from marine sponges"TEXT:Natural Products play an important role in the prevention and therapeutic system for human healthy. 50% of drugs in the market are based on natural products and 80% of world depends still from traditional medicine. The drug development process from natural sources is a long and complex way. Recently, several improvements in each step of this process have been determinant for a reinterest from pharmaceutical companies in these kinds of compounds.The chemical synthesis has a relevant role in the drug development process: it allows assuring about identity of compounds, obtaining the bioactive compound in large scale to develop the clinical trial and satisfy the pharmaceutical market demands. The introduction of solid-phase chemistry has been one of the most important improvements in chemical synthesis area because it allows a rapid and efficient exploration about strategic synthetic routes. It has been wide used in peptides and oligonucleotides synthesis and especially useful in cyclic depsipeptides produced by marine microorganism. In the present thesis, is described the development of solid-phase synthesis for two new cyclic depsipeptides, syrengotoxin and thiocoraline with the aim to contribute in its medical use.Syrengotoxin is a cyclic lipononadepsipeptide produced by a pathogen bacterium that shows interesting activity against Leishmania parasite. In this project, it has been designed a analogue peptide which preserve all structural features and the configuration of peptide chain respect natural peptide. The defined synthesis is compatible with syrengotoxin synthesis. It has been developed the non-natural amino acids presents in natural compound and its correct incorporation in the peptide chain.The thiocoraline is a symmetric biclyclic peptide which is produced by a marine microorganism and presents a potent activity as an antitumoral drug. In this project, it has been developed a solid-phase synthesis of a more resistant in plasma analogue. In this case it has been resolved the N-methyl non natural amino acids synthesis that are also present in natural compound.Lastly, it has been isolated new antitumoral compounds from marine sponges collected from south-east Australian coasts which the aim to obtain new drugs and improve the knowledge about drug development from natural sources.