Bioactive Sesterterpenes and Triterpenes from Marine Sponges: Occurrence and Pharmacological Significance

Marine ecosystems (>70% of the planet’s surface) comprise a continuous resource of immeasurable biological activities and immense chemical entities. This diversity has provided a unique source of chemical compounds with potential bioactivities that could lead to potential new drug candidates. Many marine-living organisms are soft bodied and/or sessile. Consequently, they have developed toxic secondary metabolites or obtained them from microorganisms to defend themselves against predators [1]. For the last 30–40 years, marine invertebrates have been an attractive research topic for scientists all over the world. A relatively small number of marine plants, animals and microbes have yielded more than 15,000 natural products including numerous compounds with potential pharmaceutical potential. Some of these have already been launched on the pharmaceutical market such as Prialt® (ziconotide; potent analgesic) and Yondelis® (trabectedin or ET-743; antitumor) while others have entered clinical trials, e.g., alpidin and kahalalide F. Amongst the vast array of marine natural products, the terpenoids are one of the more commonly reported and discovered to date. Sesterterpenoids (C25) and triterpenoids (C30) are of frequent occurrence, particularly in marine sponges, and they show prominent bioactivities. In this review, we survey sesterterpenoids and triterpenoids obtained from marine sponges and highlight their bioactivities

Nouvelles applications des sulfoxydes en synthèse asymétrique (Réaction de type reformatsky et de cyclisation réductrice)

Deux étapes clé impliquant la participation du groupement sulfinyl comme inducteur de chiralité ont été utilisés pour créer trois de cinq centres asymétriques présent dans le fragment C15-C26 de la ( )-dictyostatine. Premièrement, la réaction de type Reformatsky asymétrique en présence de SmI2 et un aldéhyde chiral nous a permis d obtenir un stéréoadduit majoritaire avec une très bonne sélectivité syn, pour la création de deux nouveaux centres stéréogènes. Deuxièmement, la réduction diastéréosélective avec DIBALH du -cétosulfoxyde résultant de ce couplage de type Reformatsky a servi à générer le troisième centre obtenant ainsi le 1,3-syn-diol présente dans le fragment envisagé. La synthèse a été menée avec succès en 13 étapes avec un rendement global de 24% à partir de l ester de Roche (S) commercialement disponible comme produit de départ.La préparation des unités tétrahydropyranniques par une séquence réactionnelle qui débute par une réaction de type Reformatsky asymétrique suivie d une cyclisation réductrice a été réalisée avec succès sur deux séries d aldéhydes. Deux séries de tétrahydropyrannes trisubstitués ont été synthétisés. La première partante d un diol-1,3-syn et la deuxième partant d un diol-1,3-anti. Dans les deux cas, nous avons constaté la perte de l hydroxyle de cette unité qui ne participe pas dans l étape de cyclisation réductrice. Cette approche synthétique a été par la suite appliquée à la synthèse du fragment C1 C8 du ( )-herboxidiène. La synthèse arrivant à un intermédiaire tétrahydropyrannique clé a été réalisée en 11 étapes avec un rendement de 3.6%.The sulfinyl group as chiral inductor was used to generate three of the five asymmetric centres in the fragment C15-C26 of the ( )-dictyostatine. First, the Reformatsky reaction type in presence of SmI2 and a chiral aldehyde gave rise with high stereoselection to the syn adduct so two new stereocenters were installed. Secondly, the reduction by DIBALH of the resulting -ketosulfoxyde gave the 1,3-syn-diol present in the fragment. The synthesis was accomplished successfully in 13 steps and 24% yield from the commercially available Roche s ester as starting material.The preparation of tetrahydropyranic units by a reaction sequence which involves a Reformatsky type reaction was tested with two different aldehydes. The synthetic sequence followed by a diastereoselective reduction and a reductive cyclisation process. Two series of tetrahydropyrans were synthesized one form a 1,3-syn-diol and a second from a 1,3-anti-diol. In both cases, we observed the lost of one hydroxyl group. This synthetic approach was applied to the preparation of the C1 C8 fragment of the ( )-herboxidiene. which was achieved in 11 steps and a 3.6% global yield.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceSpainFRE

Highly Stereoselective Total Synthesis of (+)-9-epi-Dictyostatin and (–)-12,13-bis-epi-Dictyostatin Eur. J

19 páginas, 9 esquemas, 2 tablas -- PAGS nros. 2643-2661The total syntheses of (+)-9-epi-dictyostatin (1a) and (–)-12,13-bis-epi-dictyostatin (1b), diastereomers of the antimitotic marine sponge-derived macrolide (–)-dictyostatin (1), were achieved by creating 11 stereogenic centers and 4stereogenic double bonds with a high level of stereocontrol. The yield for the 29-step longest linear sequence from Roche ester was 1.53 and 1.52 %, respectively. The final key steps to these unnatural products were the addition of vinylzincates C10-C26 to aldehyde C1–C9 (leading surprisingly to complete stereoselectivity for the 9R-configuration in 28a and for the 9S-configuration in 12,13-bis-epimeric 28b), followed by Yamaguchi macrolactonization and global deprotection. (–)-12,13-Bis-epi-dictyostatin (1b) displayed a dramatic decrease of cytotoxicity and of the affinity toward the paclitaxel binding site of microtubulesWe thank the Ministero dell'Università e della Ricerca (MIUR) for financial support (PRIN prot. 2008J4YNJY) and for a PhD fellowship (Borsa di dottorato, Progetto giovani, to C. Z.). L. P. thanks Milan University for a postdoctoral fellowship (Assegno di ricerca). Z. H. (Lanzhou University, PRC) thanks the China Scholarship Council for a PhD mobility grant. J. F. D. thanks the Spanish Ministerio de Ciencia e Innovación (MICINN) for support (grant number BIO2010-16351Peer reviewe