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Chemical investigation of the South-Pacific marine sponge Suberea clavata led to the isolation of eight new bromotyrosine metabolites named subereins 1–8 (2–9) along with twelve known co-isolated congeners. The detailed configuration determination of the first representative major compound of this family 11-epi-fistularin-3 (11R,17S) (1) is described. Their chemical characterization was achieved by HRMS and integrated 1D and 2D NMR (nuclear magnetic resonance) spectroscopic studies and extensive comparison with literature data. For the first time, a complete assignment of the absolute configurations for stereogenic centers C-11/17 of the known members (11R,17S) 11-epi-fistularin-3 (1) and 17-deoxyfistularin-3 (10) was determined by a combination of chemical modifications, Mosher’s technology, and ECD spectroscopy. Consequently, the absolute configurations of all our new isolated compounds 2–9 were determined by the combination of NMR, Mosher’s method, ECD comparison, and chemical modifications. Interestingly, compounds 2–7 were obtained by chemical transformation of the major compound 11-epi-fistularin-3 (1). Evaluation for acetylcholinesterase inhibition (AChE), DNA methyltransferase 1 (DNMT1) modulating activity and antifouling activities using marine bacterial strains are also presented.

Four new brominated tyrosine metabolites, aplyzanzines C&ndash, F (1&ndash, 4), were isolated from the French Polynesian sponge Pseudoceratina n. sp., along with the two known 2-aminoimidazolic derivatives, purealidin A (5) and 6, previously isolated, respectively, from the sponges Psammaplysilla purpurea and Verongula sp. Their structures were assigned based on the interpretation of their NMR and HRMS data. The compounds exhibited quorum sensing inhibition (QSi) and antifouling activities against several strains of bacteria and microalgae. To our knowledge, the QSi activity of this type of bromotyrosine metabolite is described here for the first time.

International audience; Four new brominated tyrosine metabolites, aplyzanzines C-F (1-4), were isolated from the French Polynesian sponge Pseudoceratina n. sp., along with the two known 2-aminoimidazolic derivatives, purealidin A (5) and 6, previously isolated, respectively, from the sponges Psammaplysilla purpurea and Verongula sp. Their structures were assigned based on the interpretation of their NMR and HRMS data. The compounds exhibited quorum sensing inhibition (QSi) and antifouling activities against several strains of bacteria and microalgae. To our knowledge, the QSi activity of this type of bromotyrosine metabolite is described here for the first time.

WOS:000518678100003; Although the French Polynesian reefs are among the most well studied reefs of the world, sponges are still poorly known, with only 199 species or OTUs of sponges having been described from French Polynesia, 167 at an OTU level and 32 at a species level. From those 199 species, just five are calcareous sponges. As it is possible that this number is underestimated, the aim of the present work was to study the diversity of calcareous sponges from French Polynesia. Hence, different French Polynesian archipelagos were surveyed by SCUBA from 3 to 60 m of depth. Identifications were performed using morphological and molecular (ITS and C-LSU) tools. We found a total of nine species of Calcarea, comprising five different genera. Five species are new to science: Clathrina fakaravae sp. nov., Clathrina huahineae sp. nov., Ernstia variabilis sp. nov., Leucascus digitiformis sp. nov., and Leucandra tahuatae sp. nov. With the present work, the number of identified sponges from French Polynesia at a species level increased from 32 to 41. The only calcareous sponge previously known from French Polynesia that was recollected by our group was Leucetta chagosensis. Our results suggest that the Eastern Indo-Pacific Realm shows more affinity with the Central and the Western Indo-Pacific Realms Four species supported these affinities: Ascandra cf. crewsi, previously known only from Papua New Guinea, Leucascus simplex from South Australia, and Leucetta chagosensis and L. microraphis, both widespread species in the Indo-Pacific. These two Leucetta species, however, most likely represent species complexes. Once again the molecular markers ITS and C-LSU helped in the identification of calcareous sponges, showing how important is an integrative taxonomy. Although our work has increased in 250% (6 spp to 15 spp) the diversity of calcareous sponges in French Polynesia, it is most possible that this number is still underestimated.

Treatment of acute myeloid leukemia (AML) patients is still hindered by resistance and relapse, resulting in an overall poor survival rate. Recently, combining specific B-cell lymphoma (Bcl)-2 inhibitors with compounds downregulating myeloid cell leukemia (Mcl)-1 has been proposed as a new effective strategy to eradicate resistant AML cells. We show here that 1(R), 6(S), 1&rsquo, (R), 6&rsquo, (S), 11(R), 17(S)-fistularin-3, a bromotyrosine compound of the fistularin family, isolated from the marine sponge Suberea clavata, synergizes with Bcl-2 inhibitor ABT-199 to efficiently kill Mcl-1/Bcl-2-positive AML cell lines, associated with Mcl-1 downregulation and endoplasmic reticulum stress induction. The absolute configuration of carbons 11 and 17 of the fistularin-3 stereoisomer was fully resolved in this study for the first time, showing that the fistularin we isolated from the marine sponge Subarea clavata is in fact the (+)-11(R), 17(S)-fistularin-3 stereoisomer keeping the known configuration 1(R), 6(S), 1&rsquo, (R), and 6&rsquo, (S) for the verongidoic acid part. Docking studies and in vitro assays confirm the potential of this family of molecules to inhibit DNA methyltransferase 1 activity.

Herein, we describe the isolation and spectroscopic identification of eight new tetrabrominated tyrosine alkaloids 2–9 from the Polynesian sponge Suberea ianthelliformis, along with known major compound psammaplysene D (1), N,N-dimethyldibromotyramine, 5-hydroxy xanthenuric acid, and xanthenuric acid. Cytotoxicity and acetylcholinesterase inhibition activities were evaluated for some of the isolated metabolites. They exhibited moderate antiproliferative activity against KB cancer cell lines, but psammaplysene D (1) displayed substantial cytotoxicity as well as acetylcholinesterase inhibition with IC50 values of 0.7 μM and 1.3 μM, respectively.

WOS:000430461000007; International audience; A new species of Raspailia (Raspaxilla) frondosa sp. nov. is described from the deep seamounts of the Norfolk and New Caledonia Ridges. The morphology of the species resembles that of a frond or a fern, and its unique highly compressed axial skeleton of interlaced spongin fibres without spicules in combination with a radial extra axial skeleton of a perpendicular palisade of spicules, differentiate it from all other species of the subgenus. This species is compared morphologically to all 18 other valid species described in Raspailia (Raspaxilla).

WOS:000449495400028; International audience; Marine sponges are prolific producers of physiologically active secondary metabolites [1, 2]. The chemical exploration of fatty acids derived from of marine organisms is a vital research area [3,4,5]. Fatty acids and lipids obtained from marine sources display unique molecular diversity, including saturated, mono-, di-, and polyunsaturated, branched, halogenated, hydroxylated, methoxylated, epoxide, and non-methylene-interrupted structure [6]. Marine fatty acids exhibit a variety of bioactivities, including antifungal, antibacterial, antimalarial [7], and anticancer [8]. Among the marketed eight marine-derived drugs, the ethyl esters of several omega-3 fatty acids from fish oils, in particular, ethyl esters of the major constituents eicosapentaenoic acid and docosahexaenoic acid, are approved as anti-hypertriglyceridemia and antibacterial drugs [9,10,11].

WOS:000413167100012; International audience; Guided by a "chemistry first" approach using molecular networking, eight new bright-blue colored natural compounds, namely dactylocyanines A-H (3-10), were isolated from the Polynesian marine sponge Dactylospongia metachromia. Starting from ilimaquinone (1), an hemisynthetic phishing probe (2) was prepared for annotating and matching structurally related natural substances in D. metachromia crude extract network. This strategy allowed characterizing for the first time in Nature the blue zwitterionic quinonoid chromophore. The solvatochromic properties of the latter are reported.

Two new acyclic bis-guanidine alkaloids, unguiculins B-C (2–3), were isolated from a French Polynesian sponge Monanchora n. sp. together with the known compound unguiculin A (1). Their structures were established by spectroscopic data interpretation and comparison with the literature. Unguiculins A-C displayed antiproliferative and cytotoxic efficacy against several human cancer cells with IC50 values in the micromolar range.

WOS:000416240300004; International audience; The Indo-Pacific is the world's largest marine biogeographic region, covering the tropical and subtropical waters from the Red Sea in the Western Indian Ocean to the Easter Islands in the Pacific. It is characterized by a vast degree of biogeographic connectivity in particular in its marine realm. So far, usage of molecular tools rejected the presence of cosmopolitan or very widespread sponge species in several cases, supporting hypotheses on a higher level of endemism among marine invertebrates than previously thought. We analysed the genetic diversity of Hyrtios erectus and Stylissa massa, two alleged widespread sponge species of the Indo-Pacific, from the Red Sea and Mayotte in the West Indian Ocean to Polynesia in the Central Pacific. In the region of its type locality, the Red Sea, Hyrtios erectus is genetically distinct, and the populations from the remaining Indo-Pacific are a potentially different species and paraphyletic in respect to H. altus. Stylissa massa falls into different, but widespread genetic clades, one of them (Stylissa cf. massa), with distinct potentially hairpin-forming elements in mitochondrial intergenic regions. The results also indicate that morphologically established demosponge species in the Indo-Pacific can be widespread, but simultaneously harbour cryptic, genetically distinct lineages.

00000; International audience; Dactylospongia metachromia and Dactylospongia elegans collected from French Polynesia were studied with a particular focus on the variation of the diastereomeric ratio between ilimaquinone (4) and 5-epi-ilimaquinone (5). More than 100 samples, covering an area of 4100km(2), were studied to try to clarify this intriguing issue. Nuclear magnetic resonance appeared as the non-destructive, straightforward technique of choice for a relative quantitative study. A random distribution, unique at that point in nature, is observed and leads to biosynthetic considerations. Biological evaluation of both compounds was also performed and showed moderate discrepancies in cytotoxicity and apoptosis induction.

WOS:000414234400035; International audience; Two sporothriolide-related compounds were obtained from an extract of the fungus Hypoxylon monticulosum CLL-205, isolated from a Sphaerocladina sponge collected from the Tahiti coast. Compound 2 is a deoxy analogue of sporothric acid (4). Compound 3 is a newly reported unusual scaffold combining sporothriolide (1) and trienylfuranol A (5) moieties, through a Diels-Alderase-type reaction. Various experimental and analytical arguments supported the biocatalytic origin of compound 3. The structures of the isolated compounds were elucidated using 1D and 2D NMR, HRMS, and IR data. The structure and the absolute configuration of 3 were unambiguously confirmed by a single-crystal X-ray diffraction analysis.

WOS: 000412959500037, PubMed: 28185932, Since the discovery of chitin in skeletal structures of sponges (Porifera) in 2007, studies on search of novel species which possess this structural aminopolysaccharide continue up today. The most potential source of chitin is suggested to be localized in the four families of sponges related to the order Verongida (Demospongiae) which nevertheless require further clarification. Here, we report for the first time the isolation and identification of alpha-chitin from the Suberea clavata demosponge (Aplysinidae: Verongida). Raman spectroscopy, Calcofluor White staining, chitinase test and ESI-MS techniques were used to identify chitin. We suggest that the presence of chitin within fibrous skeletons of diverse species of Verongida order, and, especially in all species of the Aplysinidae family, may be useful for the identification of novel, previously unidentified marine demosponges. (C) 2017 Elsevier B.V. All rights reserved., DFG (Germany) [EH 394-3]; PUT research grant (Poland) [03/32/DSPB/0706/2017], This work was supported by DFG Grant EH 394-3 (Germany) and PUT research grant 03/32/DSPB/0706/2017 (Poland). The authors thank Prof. Dr. Yixin Zhang for the use of the ESI-MS instrument and Rob van Soest for his support and comments.

International audience; In our ongoing search for new pharmacologically active leads from Solomon organisms, we have examined the sponge Theonella swinhoei. Herein we report the isolation and structure elucidation of swinholide A (1) and one new macrolide, swinholide J (2). Swinholide J is an unprecedented asymmetric 44-membered dilactone with an epoxide functionality in half of the molecule. The structural determination was based on extensive interpretation of high-field NMR spectra and HRESIMS data. Swinholide J displayed potent in vitro cytotoxicity against KB cells (human nasopharynx cancer) with an IC(50) value of 6 nM.

The debromokeramadine ( 2a ), which was isolated from the Pacific sponge Agelas cf. mauritiana , is described in this manuscript. We also report the synthesis of the debromokeramadine ( 2a ) and its known brominated analog, keramadine ( 1 ), based on the regioselective oxidative addition of a guanidine derivative on N -acylpyrrole dihydropyridines. This flexible approach was applied to the preparation of three debromo-analogs 2b – d by varying the substitution of the guanidine bis-nucleophile. The reaction is a great progress for the regio- and stereoselective synthesis of debromokeramadine ( 2a ) analogs and interesting library of pyrrole-2-aminoimidazole allowing biological activity studies.

International audience; Symbioses with the dinoflagellate Symbiodinium are widespread among marine invertebrates and protists, especially in nutritionally demanding habitats, such as tropical coral reefs, where they play a major role in ecosystem survival. Moreover, apart from corals and sea anemones, many of the Symbiodinium species and clades involved in these partnerships remain to be characterized. This study provides new insights into nudibranch and sponge associations with Symbiodinium by sequencing regions of the Symbiodinium 28S rDNA and the host mitochondrial COI oxidase. Specimens were sampled between 2011 and 2013 from locations around the islands of Moorea and Tahiti, French Polynesia. Our results revealed that some of the sponges and nudibranchs harbored typical Symbiodinium from clade B or C while others harbored new, undescribed Symbiodinium-like dinoflagellates. A detailed analysis of the different life stages of the nudibranch Phestilla lugubris and of its specific coral prey, Porites rus, suggests a prey-predator horizontal transfer of the symbiont and its vertical inheritance from the parent to the eggs.; Les symbioses à zooxanthelles, dinoflagellés du genre Symbiodinium, sont largement répandues chez les invertébrés marins et les protozoaires, notamment dans les eaux oligotrophes, où ils jouent un rôle important dans la survie des récifs coralliens. De plus, excepté chez les coraux et les anémones, les différentes espèces et clades de Symbiodinium impliqués dans ces associations restent à être caractérisés. Notre étude, grâce à l’utilisation des marqueurs génétiques 28S ADNr des Symbiodinium et la sous-unité 1 de la cytochrome oxydase mitochondriale (COI) de l’hôte, procure de nouvelles données quant aux associations des éponges et des nudibranches avec les Symbiodinium. L’échantillonnage a eu lieu autour de Moorea et de Tahiti (Polynésie française), entre 2011 et 2013. Nos résultats révèlent que certaines espèces d’éponges et de nudibranches possèdent les clades B et C communément retrouvés, chez les coraux notamment, alors que d’autres présentent de nouveaux dinoflagellés « Symbiodinium-like ». Une analyses détaillée des Symbiodinium à différents stades du cycle de vie du nudibranche corallivore Phestilla lugubris et de son corail hôte Porites rus suggèrent l’existence d’un transfert horizontal de Symbiodinium proie–prédateur et un transfert vertical du parent P. lugubris à ses œufs.

Seven 2,5-diketopiperazines (DKPs) were isolated from the Fijian marine sponge Acanthella cavernosa. NMR and circular dichroism (CD) comparison with synthetic L-L DKPs allowed us to determine unambiguously the L-L absolute configuration of the natural DKPs. This work initiated the setting up of an optical properties database of natural DKPs, including specific rotation and CD. 2,5-Diketopiperazines (DKPs) are cyclic secondary metabolites directly resulted from the primary peptidic metabolites. They have been detected in beverages, foods and microorganisms. As the smallest cyclic peptides, DKPs provide interesting biological properties such as organoleptical, antitumoral, antifungal, antibacterial, antifouling and antiviral activities. 2 Many natural metabolites including alkaloids are biosynthetically derived from diketopiperazines by oxidation and rearrangement reactions. They represent an interesting tool for medicinal chemistry since their heterocyclic cores provide a good template for further chemical and stereochemical modification. Proline (Pro) and arginine (Arg) units are usually found in biologically active DKPs. Despite the increasing interest of DKPs, their stereochemical information was not well documented. DKP derivatives have attracted significant attention because of their potential rule as important class of multifunctional biomolecules. Their putative roles as signaling molecules in the chemical ecology context is more and more considered. Thus, determination of absolute configuration of cyclic dipeptides is of significant importance. As a part of our on-going research on bioactive natural compounds from Pacific Axinellidae marine sponges, a scrutinized study of secondary metabolites of a Fijian sample of the marine sponge Acanthella HETEROCYCLES, Vol. 90, No. 2, 2015 1351

The analysis of two Thorectidae sponge samples, Hyrtios sp. and Petrosaspongia sp., collected at Fiji Islands, led to the isolation of five new scalarane derivatives along with fifteen known compounds. Their structures were elucidated on the basis of NMR and MS spectroscopic data. The small library of natural scalarane derivatives was investigated for their ability to modulate the activity of trans-activation response DNA-binding protein of 43 kDa (TDP-43), a key factor in several neurodegenerative conditions and the study resulted in the identification of potent inhibitors of TDP-43 protein.

Metabolites isolated from marine invertebrates, callipeltin A 1, crambescidin 2, ptilomycalin A 3, celeromycalin 4, gymnochrome B 5, gymnochrome D 6 and isogymnochrome D 7 previously shown bioactive on either herpes simplex virus 1 (2, 3, 4) or human immunodeficiency virus (1, 5, 6, 7), were tested on a new in vitro bioassay using the dengue virus 1. Only gymnochrome D and isogymnochrome D isolated from the living fossil crinoid Gymnocrinus richeri are highly potent dengue antiviral agents.

Leucascandrolide A ((+)-1), a doubly O-bridged 18-membered macrolide of a new type, i.e., showing little C1-branching vs. extensive 1,3-dioxygenation and a peculiar side chain, was isolated from a calcareous sponge of a new genus, Leucascandra caveolata BOROJEVIC and KLAUTAU from the Coral Sea. Transesterification of (+)-1 gave the methyl ester 3, derived from the side chain, and the 5-hydroxy derivative (+)-2, derived from the macrolide portion and with the natural configuration at C(5) (axial). Mosher's MTPA esters 4 and 5 obtained from (+)-2 showed scattered Δδ = (δ(S) − δ(R)) data. However, inversion of the configuration at C(5) led, via ketone (+)-6, to the less encumbered 5-equatorial hydroxy derivative (+)-7, whose MTPA esters 8 and 9 gave consistent Δδ data, allowing the assignment of the absolute configuration of (+)-7, and hence of (+)-1. The structural novelty of (+)-1 and its powerful antifungal and cytotoxic activities are likely to renew interest in calcareous sponges, previously limited to scarcely biologically active 2-aminoimidazoles.

From the cytotoxic extracts of the marine ascidian Leptoclinides dubius, N-(p-hydroxybenzoyl)-l-arginine (1), N-(1H-indolyl-3-carbonyl)-d-arginine (2), and N-(6-bromo-1H-indolyl-3-carbonyl)-R, where R is l-Arg (4), l-His (5), and the very rare amino acid l-enduracididine (3), have been isolated and identified by spectroscopic data, hydrolysis, and comparison with authentic samples.

Onchidin B (4) is a cyclic depsipeptide isolated from the pulmonate mollusc Onchidium sp. Its structure was determined by extensive 2D-NMR, FABMS, tandem FAB MS/MS, selective hydrolysis, and synthesis. It contains four α-amino acids [two units of N-methyl valine (MeVal), two units of proline (Pro)], four α-hydroxy acids [two 2-hydroxyisovaleric acids (Hiv), two 2-hydroxy-3-methylpentanoic acid moieties (Hmp)] and two units of the new β-hydroxy acid: 3-hydroxy-2-methyloct-7-ynoic acid (Hymo)]. Selective hydrolysis and direct comparison by chiral GC-MS with authentic samples of the α-amino and α-hydroxy acids allowed us the assignment of the entire absolute stereochemistry of onchidin B. In this way, the α-hydroxy acids were found to be (S)-Hiv and (S,S)-Hmp, and the α-amino acids (R)-proline, (S)-proline, and (R)-MeVal. In order to establish the absolute configuration of the new β-hydroxy acid, Hymo, its four possible stereoisomers were stereoselectively synthesized using chiral N-propionyl oxazolidinones...

The known metabolite heteronemin was isolated from the marine sponge Hyrtios reticulata Thiele, using a bioguided fractionation with the enzyme protein farnesyl transferase as a target (IC50 = 3 µM). In contrast, 12-epi-heteronemin, isolated from a related sponge, Hyrtios erecta Keller, did not show any noticeable inhibitory activity.

Caledonin (1) is a modified peptide isolated from the marine tunicate Didemnun rodriguesi . Caledonin comprises a central L-phenylalanine residue connected via its amino group to ( S )-3-amino-5-mercaptopentanoic acid (a new sulfur-containing β-amino acid), and by its carboxyl group to a six membered cycloguanidine moiety, bearing an n -octyl chain. Caledonin is a natural bolaphile which strongly binds Zn II and Cu I ions.

International audience; Pipestelides A-C (2-4) are three new NRPS-PKS hybrid macrolides containing uncommon moieties, isolated from the Pacific marine sponge Pipestela candelabra. Their structures were elucidated on the basis of spectroscopic data. These cyclodepsipeptides appear to be biosynthetically related to jaspamide (aka jasplakinolide) (1) by chemical modification of the building blocks of the polyketide or peptide chains. Pipestelides A-C (2-4) contain a bromotyrosine [3-amino-3-(bromo-4-hydroxyphenyl)propanoic acid] unit, a polypropionate with a Z double bond, and a 2-hydroxyquinolinone, respectively. Revised chemical shift assignments are provided for the co-isolated known jasplakinolide C(a) (5). In addition, compounds 2 and 3 exhibited cytotoxic activities in the micromolar range.

We report the isolation and pharmacological characterization of conicasterol E isolated from the marine sponge Theonella swinhoei. Pharmacological characterization of this steroid in comparison to CDCA, a natural FXR ligand, and 6-ECDCA, a synthetic FXR agonist generated by an improved synthetic strategy, and rifaximin, a potent PXR agonist, demonstrated that conicasterol E is an FXR modulator endowed with PXR agonistic activity. Conicasterol E induces the expression of genes involved in bile acids detoxification without effect on the expression of small heterodimer partner (SHP), thus sparing the expression of genes involved in bile acids biosynthesis. The relative positioning in the ligand binding domain of FXR, explored through docking calculations, demonstrated a different spatial arrangement for conicasterol E and pointed to the presence of simultaneous and efficient interactions with the receptor. In summary, conicasterol E represents a FXR modulator and PXR agonist that might hold utility in treatment of liver disorders.

DCCC chromatography followed by HPLC purification on the polar extract of marine sponge Theonella swinhoei resulted in the isolation of five new cyclopeptides, perthamides G–K. The new structures, featuring unprecedented amino acid units, were determined by interpretation of extensive spectroscopic and spectrometric data (MS, 1 H and 13 C NMR, COSY, HSQC, HMBC, and ROESY). Pharmacological analysis demonstrated that these natural cyclopeptides are endowed with anti-inflammatory potential as assessed by their ability to reduce carrageenan-induced mouse paw oedema.

Onchidin (1) is a cytotoxic depsipcptide isolatcd from thc pulmonate mollusc Onchidium sp. Its structure is cyclo (MeVal-Amo-Val-Hiv-Hiv-McVal-Amo-Val-Hiv-Hiv) made or two identical halves (C3OH49N307, MeVal-Amo-Val-Hiv-Hiv). Onchidin contains a new s-amino acid: 3-amino-2-methyl- oct-7-ynoic acid (Amo). It has C2-symmetry and this makcs one half homotopic to the other so only signals for a "monomer" can be seen in the NMR spectra. Thc structure and absolute stereochemistry' (all S) of onchidin was determined by extcnsivc spcctroscopic analysis, selective hydrolysis and chiral GCMS. Cyclic peptides with important pharmacological properties have been isolated from manne 0rganisms.l Frequently these metabolites contain D amino acids, hydroxy acids, new a-amino acids, new s-amino acids and thiazole and oxazole rings. In some cases, the cyclic structure incorporates elements of symmetry that complicate the structural determination due to the bonding possib es of the repeating fragments and the simplification of the spectra. The interest of these compounds is well illustrated by dolastatin- IO, the most potent antineoplastic agent known2 and by the didemnins,3 considered as some of the most promising antitumor compounds of marine origin. In this paper we describe the structure (including absolute configuration) of onchidin (1) a new cytoxic depsipeptide with C2 symmetry isolated from a pulmonate mollusc known to be a rich source of y- pyrone poIypropionates4. Onchidium sp. (Pulmonatu, order: Sryfommarophora) (3Kg. fresh weight) collected off New Caledonia was extracted with methanol. P-388 and Kb activity-guided fractioning by solvent partition followed by repeated chromatography (Sephadex, reverse phase HPLC) afforded 3 mg of a pure compound ((a)&'=-140.9'; P-388

A highly cytotoxic macrolide, superstolide A (1), has been isolated from the deep water marine sponge Neosiphonia superstes, collected off New Caledonia. The gross structure was determined by extensive 2D NMR experiments on the lactone 1 and on its opened-ring-derived methyl esters 2 and 3. The relative stereochemistries of the decaline moiety and of the C22-C26 fragment were determined by a combination of NMR data and acetonide analysis on 2. Absolute stereostructure of the decaline portion of 1 has been determined on the basis of GLC-modified Horeau's methodology applied to 4, whereas the results of the application of the modified Mosher's method to 1 and 3 allowed us to propose for the C22-C26 fragment the 22R, 23R, 24R, 25S, 26R configuration. We also propose the solution conformations of superstolide A (1) based on molecular dynamics and mechanics calculations using NMR-derived constraints.

Ten novel polyhydroxylated 9,11-secosterols, 1–10, have been isolated from the New Caledonian sponge Euryspongia sp. and their structures elucidated by spectroscopic studies, selective acetylation and reduction, leading to the complete assignment of all the NMR signals. Euryspongiols A1–A5 differ in their side chains but have the same 2α,3β,4α,6β,11,19 hexahydroxy-9,11-secocholestane skeleton. Euryspongiols B1–B5 are the corresponding 3α epimers. Compounds 1–10 are the most highly hydroxylated secosteroids isolated so far, and are the first hydroxylated at C-4. NaBH4 reduction of the carbonyl group at C-9 of 1 and 2 is stereospecific, producing the heptahydroxylated secosteroids 1a and 2b with a β C-9 hydroxyl group. Compounds 1 and 2 have been found to strongly inhibit the release of histamine from rat mastocysts.

Three new manoalide-related sesterterpenes, fasciospongides A [1], B [2], and C [3], have been isolated from the sponge Fasciospongia sp. and their structures elucidated by spectral methods

Two unprecedented cyclic peptides, solomonamides A and B, were isolated from the marine sponge Theonella swinhoei. The structures were elucidated on the basis of comprehensive 1D and 2D NMR analysis and high-resolution mass spectrometry. A combined approach, involving Marfey's method, QM J based analysis, and DFT J/(13)C calculations, was used for establishing the absolute configuration of the entire molecule. Solomonamide A showed in vivo anti-inflammatory activity.

International audience; Indole derivatives including bromoindoles have been isolated from the South Pacific marine sponges Rhopaloeides odorabile and Hyrtios sp. Their structures were established through analysis of mass spectra and 1D and 2D NMR spectroscopic data. Their potential inhibitory phospholipase A₂ (PLA₂), antioxidant and cytotoxic activities were evaluated. The new derivative 5,6-dibromo-L-hypaphorine (9) isolated from Hyrtios sp. revealed a weak bee venom PLA₂ inhibition (IC₅₀ 0.2 mM) and a significant antioxidant activity with an Oxygen Radical Absorbance Capacity (ORAC) value of 0.22. The sesquiterpene aureol (4), also isolated from Hyrtios sp., showed the most potent antioxidant activity with an ORAC value of 0.29.

Theirintriguingdimeric polycyclic ring systems that were isolated during thelast years revealed their elaborate structures and moleculardiversity which arise from a variety of modes of dimerizationand polycyclization. Structurally, it is assumed that thesemetabolites arise from the crucial intermediates clathrodin

International audience; Bioassay-directed fractionation of South Pacific marine sponges of the genus Xestospongia has led to the isolation of a number of halenaquinone-type polyketides, including two new derivatives named xestosaprol C methylacetal 7 and orhalquinone 8. Chemical characterization of these two new compounds was achieved by extensive 1D and 2D NMR spectroscopic studies. Evaluation of anti-phospholipase A(2), anti-farnesyltransferase and antiplasmodial activities of this series is presented and structure/activity relationships are discussed. Orhalquinone 8 displayed a significant inhibition of both human and yeast farnesyltransferase enzymes, with IC(50) value of 0.40 microM and was a moderate growth inhibitor of Plasmodium falciparum.

1. 1. The hitherto undescribed sterol compositions of three marine sponge species belonging to the genus Cinachyrella are reported: C. alloclada and C. kukenthali from the Senegalese coast, at two different depths, and C. aff. schulzei from the lagoon of Noumea, New Caledonia. 2. 2. Fourteen free sterols have been identified by GC and GC/MS studies, including the 23,24ξ-dimethylcholesta-5,22-dien-3β-ol (10) and the rare 24-norcholesta-5,22-dien-3β-ol (1). 3. 3. The first compound (10) is reported for the second time in a marine sponge and it was found only in Senegalese sponges collected in shallow waters. 4. 4. Sterol (10) has been isolated by HPLC and identified by NMR techniques. 5. 5. Significant amounts of cholest-7-en-3β-ol (7) were also found in the Senegalese sponge species. 6. 6. Apart from these two compounds, the three sponge sterol compositions are found to be very similar.

Eight new polypropionate-derived esters (5-8 and 10-13) have been isolated from pulmonate molluscs of the genus Onchidium collected in the South Pacific. The structures of these compounds were determined spectroscopically in particular by one- and two-dimensional NMR and low and high EIMS. The absolute stereochemistry of the seven asymmetric centers was determined by using the Trost-Mosher methodology