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Natural Products (NP) are essential for the discovery of novel drugs and products for numerous biotechnological applications. The NP discovery process is expensive and time-consuming, having as major hurdles dereplication (early identification of known compounds) and structure elucidation, particularly the determination of the absolute configuration of metabolites with stereogenic centers. This review comprehensively focuses on recent technological and instrumental advances, highlighting the development of methods that alleviate these obstacles, paving the way for accelerating NP discovery towards biotechnological applications. Herein, we emphasize the most innovative high-throughput tools and methods for advancing bioactivity screening, NP chemical analysis, dereplication, metabolite profiling, metabolomics, genome sequencing and/or genomics approaches, databases, bioinformatics, chemoinformatics, and three-dimensional NP structure elucidation., This publication is based upon work from COST Action CA18238 (Ocean4Biotech), funded by the European Cooperation in Science and Technology (COST) Program in the period 2019–2023. SPG: This work is financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the projects UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. LLB: The publication is part of a project that has received funding from the Erasmus + Project No. ECOBIAS_609967-EPP-1-2019-1-RS-EPPKA2-CBHE-JP; GA.2019-1991/001-001. Development of master curricula in ecological monitoring and aquatic bioassessment for Western Balkans HEIs/ECOBIAS. CJ: This work was supported by grants PID2021-122732OB-C22 from MCIN/AEI/10.13039/501100011033/FEDER “A way to make Europe” (AEI, Spanish State Agency for Research and FEDER Programme from the European Union) and RTI2018-093634-B-C22 from the State Agency for Research (AEI) of Spain, co-funded by the FEDER Programme from the European Union, and BLUEBIOLAB (0474_BLUEBIOLAB_1_E), Programme INTERREG V A of Spain-Portugal (POCTEP). FP: This work is financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDB/50006/2020 of the Research Unit on Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE) and for an Assistant Research Position (CEECIND/01649/2021). MC: INTERREG-MAC2/1.1b/279 (AHIDAGRO) and the Ministerio de Ciencia e Innovación (Spain) (grant PID2020-115979RR-C32). ARDM is supported with funds from Proyecto Intramural Especial CSIC [Ref. 202280I032].

The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve di erent pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year.Marine-based pharmaceuticals have started to impactmodern pharmacology and different anti-cancer drugs derived frommarine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use., This publication is based upon work from COST Action CA18238 (Ocean4Biotech), supported by COST (European Cooperation in Science and Technology) programme. This work was partially supported by the Applied Molecular Biosciences Unit-UCIBIO (UID/Multi/04378/2019), financed by national funds from FCT/MCTES. Additionally, support was received from the FCT/MCTES through grant IF/00700/2014 (to SPG); the Slovenian Research Agency research core funding P1-0245 (to AR); TÜB˙ITAK grant number 216Z167 (to AE); the Ministerio de Ciencia e Innovación (grant RTA 2015-00010-C03-02) (to MC); the Agustin de Betancourt Programme (Cabildo de Tenerife, TFinnova Programme supported by MEDI and FDCAN funds) (to ARDM); the MetaboCell project of Canceropôle Provence-Alpes-Côte d’Azur and the Provence-Alpes-Côte d’Azur Region (to MM). This project (to OPT, Grant-Aid Agreements No. PBA/MB/16/01 and PDOC/19/02/01) was carried out with the support of the Marine Institute and funded under the Marine Research Programme by the Irish Government.

This article belongs to the Special Issue Marine Compounds and Inflammation II., Neurodegenerative diseases are age-related disorders caused by progressive neuronal death in different regions of the nervous system. Neuroinflammation, modulated by glial cells, is a crucial event during the neurodegenerative process; consequently, there is an urgency to find new therapeutic products with anti-glioinflammatory properties. Five new furanocembranolides (1-5), along with leptolide, were isolated from two different extracts of Leptogorgia sp., and compound 6 was obtained from chemical transformation of leptolide. Their structures were determined based on spectroscopic evidence. These seven furanocembranolides were screened in vitro by measuring their ability to modulate interleukin-1β (IL-1β) production by microglial BV2 cells after LPS (lipopolysaccharide) stimulation. Leptolide and compounds 3, 4 and 6 exhibited clear anti-inflammatory effects on microglial cells, while compound 2 presented a pro-inflammatory outcome. The in vitro results prompted us to assess anti-glioinflammatory effects of leptolide in vivo in a high-fat diet-induced obese mouse model. Interestingly, leptolide treatment ameliorated both microgliosis and astrogliosis in this animal model. Taken together, our results reveal a promising direct biological effect of furanocembranolides on microglial cells as bioactive anti-inflammatory molecules. Among them, leptolide provides us a feasible therapeutic approach to treat neuroinflammation concomitant with metabolic impairment., This research was funded by the Ministerio de Ciencia e Innovación (grants BFU2015-68149-R to MDG, SAF2016-77871-C2-1R to ICC, and SAF2009-0839 and RTA 2015-00010-C03-02 to MC) and by Consejería de Educación Junta Castilla y León (grant VA086G18 to MDG) and was cofinanced by European Regional Development Fund. MCG was supported by a University of Valladolid Ph.D. fellowship (call#2016). ARDM acknowledges support from Agustin de Betancourt Programme (Cabildo de Tenerife, TFinnova Programme supported by MEDI and FDCAN funds). A.B.G. would like to thank Convenio Universidad de Magallanes, programa interno PR-F2-01-CRN18-19 (Chile), and CSIC, project 2009CL0031, for financial support.

Nine new cembranoids 1–9 containing an α–methylene–γ–butyrolactone together with the known diterpenes 10–15 have been isolated from a crude extract of Eunicea sp. and their structures were established by spectroscopic methods. The proliferative effect of six of these compounds on insulin-producing cells (beta–cells) was evaluated., This work was funded by the Ministerio de Ciencia e Innovación (SAF2009-0839 and RTA 2015-00010-C03-02). ARDM acknowledges financial support from Cabildo de Tenerife and Agustin de Betancourt Programme 2016. GP acknowledges a fellowship from Programa JAE-Pre (CSIC).

This article belongs to the Special Issue Progress on Marine Natural Products as Lead Compounds., Two new chloro-furanocembranolides (1, 2) and two new 1,4-diketo cembranolides (3, 4) were isolated from the crude extract of Leptogorgia sp. together with a new seco-furanocembranolide (5) and the known Z-deoxypukalide (6), rubifolide (7), scabrolide D (8) and epoxylophodione (9). Their structures were determined based on spectroscopic evidence. Four compounds: 1, 2, 7 and 8 were found to activate the proliferation of pancreatic insulin-producing (beta) cells., This work was supported by the Ministerio de Ciencia e Innovación (SAF2009-0839 and RTA 2015-00010-C03-02). ARDM acknowledges funding from IMBRAIN project (FP7-REGPOT-2012-CT2012-31637-IMBRAIN) and from Cabildo de Tenerife (Agustín de Betancourt Programme). A.B.G. would like to thank Convenio Universidad de Magallanes (Chile) and CSIC, project 2009CL0031, for financial support.

This article belongs to the Special Issue Marine Compounds and Inflammation II, 2017., Type 2 diabetes (T2DM) is a complex disease linked to pancreatic beta-cell failure and insulin resistance. Current antidiabetic treatment regimens for T2DM include insulin sensitizers and insulin secretagogues. We have previously demonstrated that leptolide, a member of the furanocembranolides family, promotes pancreatic beta-cell proliferation in mice. Considering the beneficial effects of leptolide in diabetic mice, in this study, we aimed to address the capability of leptolide to improve insulin resistance associated with the pathology of obesity. To this end, we tested the hypothesis that leptolide should protect against fatty acid-induced insulin resistance in hepatocytes. In a time-dependent manner, leptolide (0.1 µM) augmented insulin-stimulated phosphorylation of protein kinase B (PKB) by two-fold above vehicle-treated HepG2 cells. In addition, leptolide (0.1 µM) counteracted palmitate-induced insulin resistance by augmenting by four-fold insulin-stimulated phosphorylation of PKB in HepG2 cells. In vivo, acute intraperitoneal administration of leptolide (0.1 mg/kg and 1 mg/kg) improved glucose tolerance and insulin sensitivity in lean mice. Likewise, prolonged leptolide treatment (0.1 mg/kg) in diet-induced obese mice improved insulin sensitivity. These effects were paralleled with an ~50% increased of insulin-stimulated phosphorylation of PKB in liver and skeletal muscle and reduced circulating pro-inflammatory cytokines in obese mice. We concluded that leptolide significantly improves insulin sensitivity in vitro and in obese mice, suggesting that leptolide may be another potential treatment for T2DM, This research has been funded by Sociedad Española de Diabetes (Ayudas Investigación Básica 2014), Salud Castilla y León (BIO/VA40/15) and Ministerio de Economía y Competitividad-Spain (SAF2014-58702-C2-1-R) to I.C. and Ministerio de Economía y Competitividad-Spain (SAF2014-58702-C2-2-R) to G.P., We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

The cembranoid 1 and the furanocembranolides 2–4 along with the known pukalide were isolated from Leptogorgia sp. and their structures determined spectroscopically. The 1,4-diketo-cembranoid 1 follows an oxidation pattern of C-18 that reinforces the concept of oxidation profile of C-18 as taxonomical marker for octocorals. The co-occurrence within a species of furanocembranolide/1,4-diketo-cembranoid congeners 1/2–4 raises the question about which one is the biogenetic precursor. A biogenetic pathway is proposed.

Two new cyclic peptides, microsporins A and B (7 and 8), were isolated from culture extracts of the marine-derived fungus Microsporum cf. gypseum obtained from a sample of the bryozoan Bugula sp. collected in the U.S. Virgin Islands. The structures of the new compounds were determined by extensive interpretation of 2D NMR data and by chemical methods. Microsporins A and B are potent inhibitors of histone deacetylase and demonstrate cytotoxic activity against human colon adenocarcinoma (HCT-116), as well as against the National Cancer Institute 60 cancer cell panel. The total synthesis of microsporin A on solid-phase is also reported.

The rearranged compound 1, the regular 2 and 3 and the degraded 4 are novel bisabolene-type metabolites that along with the known compounds caespitol, 8-acetylcaespitol, caespitane, caespitenone, laucapyranoid A, and furocaespitane have been isolated from the sea hare Aplysia dactylomela. The structures of these compounds were determined on the basis of spectroscopic evidence. The irregular network of 1 suggested that the halogenated epoxide 6 is a key intermediate for a unified biogenetic pathway of naturally occurring marine algal bisabolene-type metabolites.

5 pages, 4 figures, 1 table.-- Printed version published Oct 3, 2005., Three naturally occurring pyranosyl-like polyhalogenated metabolites 1–3 as well as their likely biogenetic precursor, the linear compound 4, have been isolated from the red alga Ptilonia magellanica. They are the first compounds within the genus that incorporate chlorine in their network. Compound 3 have structural features reminiscent of the universal chemical signal AI-2 (autoinducer-2) for bacterial communication., This work was supported by the Ministerio de Educación y Ciencia (PPQ2002-02494, REN2002-10485-E/ANT), and the Gobierno de Canarias DGUI (PI2002/044). M.L. acknowledges MECESUP MAG0002, Chile, for financial support.

A biogenetically interesting halogen-devoid metabolite chamigrenelactone 1, with a high oxygen-content, has been isolated from Laurencia obtusa from Isla Grande (Caribbean Panama). Its structure and stereochemistry were determined on the basis of spectral studies.

Two novel sesterterpenes 1 and 2 have been isolated from the Antarctic sponge Suberites caminatus. Their structures and relative stereochemistries were determined by spectroscopic methods. Compound 1 features a novel structural type of suberitane network, and an epimer of compound 2 seems to be the biogenetic precursor of 1 and suberitenones A and B. The exclusive prevalence of suberitane-derived sesterterpene metabolites in species of Suberites suggests that this skeleton may be a chemical marker of the genus.

4 pages, 1 figure, 2 tables.-- PMID: 11975508 [PubMed].-- Printed version published Apr 26, 2002., Three new minor linear polyhalohydroxylated marine monoterpenes, plocamenols A−C (1−3), have been isolated from the red alga Plocamium cartilagineum. The structure and relative stereochemistry of these compounds were determined on the basis of spectroscopic evidence., This work was supported by Programa Antártico Español (MCYT), FEDER (projects: 1FD97-0348- C03-03), FONDECYT (1990935), Subdirección General de Cooperación Internacional, and the Program of Cooperation between the Consejo Superior de Investigaciones Científicas (CSIC, Spain)-Universidad de Chile. A.R.D.-M. acknowledges a fellowship from the CICYT.

Pantoneurotriols 1a and 2a are acyclic polyoxygenated monoterpenes isolated from the Antarctic endemism Pantoneura plocamioides together with compounds 3 and 4. The stereochemistries of these compounds were established by spectroscopic methods and pantoneurotriols have been proposed as biogenetic precursors of pantofuranoids, uncommon monoterpenes isolated from the same species. It was interesting to find compounds 4 and 5, metabolites first isolated from Plocamium cartilagineum, in a species belonging to a different order such as P. plocamioides.

Six new polyoxygenated marine monoterpenes have been isolated from the Antarctic alga Pantoneura plocamioides. The structure and relative stereochemistry of these compounds, denominated pantopyranoids A-C (1-3), and pantoisofuranoids A-C (4-6) were determined on basis of spectroscopic evidence.

This is an open-access article distributed under the terms of the Creative Commons Attribution License., There is an urgency to find new treatments for the devastating epidemic of diabetes. Pancreatic b-cells viability and function are impaired in the two most common forms of diabetes, type 1 and type 2. Regeneration of pancreatic b-cells has been proposed as a potential therapy for diabetes. In a preliminary study, we screened a collection of marine products for b-cell proliferation. One unique compound (epoxypukalide) showed capability to induce b-cell replication in the cell line INS1 832/ 13 and in primary rat cell cultures. Epoxypukalide was used to study b-cell proliferation by [3H]thymidine incorporation and BrdU incorporation followed by BrdU/insulin staining in primary cultures of rat islets. AKT and ERK1/2 signalling pathways were analyzed. Cell cycle activators, cyclin D2 and cyclin E, were detected by western-blot. Apoptosis was studied by TUNEL and cleaved caspase 3. b-cell function was measured by glucose-stimulated insulin secretion. Epoxypukalide induced 2.5- fold increase in b-cell proliferation; this effect was mediated by activation of ERK1/2 signalling pathway and upregulation of the cell cycle activators, cyclin D2 and cyclin E. Interestingly, epoxypukalide showed protection from basal (40% lower versus control) and cytokine-induced apoptosis (80% lower versus control). Finally, epoxypukalide did not impair b-cell function when measured by glucose-stimulated insulin secretion. In conclusion, epoxypukalide induces b-cell proliferation and protects against basal and cytokine-mediated b-cell death in primary cultures of rat islets. These findings may be translated into new treatments for diabetes. © 2013 López-Acosta et al., This work was supported by ISCIII-Subdireccion Geeneral de Evaluacion y Fomento de la Investigacion, Spain (PS09/00671 and CP08/00094), Europe-FP7 Marie Curie grant (IRG-247835) and Servicio Andaluz de Salud (PI-0256/2009).

Dactylomelatriol (1), obtained from the sea hare Aplysia dactylomela, is the first naturally occurring omphalane-derived sesquiterpene from the marine environment. From this species the known chamigrene and modified bisabolene sesquiterpenes 2-6 were also isolated. The structure and relative configuration of 1 were established by spectroscopic evidence. Its chemical structure is related to omphalic acid, the unique terrestrial-derived omphalane sesquiterpene isolated from a liverwort. A biogenetic route for this compound is proposed. The antimicrobial activities of compounds 1-6 were evaluated against a panel of microorganisms., This work was supported by the Ministerio de Ciencia e Innovación (BIO2007-61745, SAF2009-08039, SAF2010-16858) and DGUI Gobierno de Canarias (PIO42005, PUB2005/030). We gratefully acknowledge A. Corrales for her technical support of this project.

3 pages, 3 figures, 1 table.-- PMID: 12088448 [PubMed].-- Printed version published Jun 28, 2002., Supporting information (2 pages) available at: http://pubs.acs.org/doi/suppl/10.1021/np010580t, Two new sesquiterpenes belonging to a novel oxacyclic structural type of chamigrene skeleton, oxachamigrene (1) and 5-acetoxyoxachamigrene (2), have been isolated from the red alga Laurencia obtusa. The structures of the compounds were determined on the basis of spectroscopic evidence. A biogenetic route for these metabolites has been proposed., This work was supported by Ministerio de Ciencia y Tecnología (MCYT), FEDER (project 1FD97-0348- C03-03), Subdirección General de Cooperación Internacional, Program of Cooperation between the Consejo Superior de Investigaciones Científicas (CSIC, Spain)-Universidad de Chile and the collaboration of CEBIMAR of Cuba. I.B. acknowledges a grant from the CICYT.

3 pages, 2 figures, 1 table.-- Printed version published Apr 1, 2002., A bromo sesquiterpene, bromocyclococanol 1, containing fused cyclopropane–cyclopentane rings leading a novel carbon skeleton has been isolated from the red alga Laurencia obtusa. The structure and stereochemistry were established by spectroscopic evidence and biogenetic considerations. A biogenetic route for this compound has also been proposed., The structure, configuration and possible biogenesis for bromocyclococanol 1 are described., This work was supported by Ministerio de Ciencia y Tecnología (MCYT), FEDER (project 1FD97-0348- C03-03), Subdirección General de Cooperación Internacional, Program of Cooperation between the Consejo Superior de Investigaciones Científicas (CSIC, Spain)- Universidad de Chile and the collaboration of CEBIMAR of Cuba. I.B. acknowledges a grant from the MCYT.

Two new steroids (1 and 2) and the known pregna-1,4,20-trien-3-one (3) have been isolated from the Pacific octocoral Carijoa multiflora. Compound 1 possesses a novel spiropregnane-based steroidal skeleton. The photochemical transformation of 3 into 1 allowed the assignment of the absolute configuration at C-10 of 1. The antibacterial activities of compounds 1 and 3 were evaluated against a panel of bacterial strains., his work was supported by the Ministerio de Ciencia e Innovación (BIO2007-61745, SAF2009-08039, SAF2010-16858). A.R.D.-M. acknowledges financial support from Programa JAE-Doc (CSIC).

The isolation and structure determination of a new chlorinated benzophenone antibiotic, pestalone (1), is described. The new compound was produced by a cultured marine fungus only when a unicellular marine bacterium, strain CNJ-328, was co-cultured in the fungal fermentation. The fungus, isolated from the surface of the brown alga Rosenvingea sp. collected in the Bahamas Islands, was identified as an undescribed member of the genus Pestalotia. The structure of 1, initially assigned with only modest confidence by combined spectral and chemical data, was confirmed by single-crystal X-ray analysis. Pestalone (1) exhibits moderate in vitro cytotoxicity in the National Cancer Institute's 60 human tumor cell line screen (mean GI(50) = 6.0 microM). More importantly, pestalone shows potent antibiotic activity against methicillin-resistant Staphylococcus aureus (MIC = 37 ng/mL) and vancomycin-resistant Enterococcus faecium (MIC = 78 ng/mL), indicating that pestalone should be evaluated in advanced models of infectious disease.

2 pages, 1 figure, 1 table.-- Article in press., Supporting information available: Figures and NMR spectra of compounds 1 and 2.-- Available at: http://pubs.acs.org/doi/suppl/10.1021/np9000976, Pronuciferine N-oxide (1), a proaporphine N-methyl-N-oxide alkaloid, along with the parent alkaloid pronuciferine (2) were isolated from Berberis coletioides. The structure of the new compound was determined by spectroscopic evidence. Compound 1 is the first naturally occurring proaporphinoid alkaloid with an N-oxide functionality., This work was supported by Universidad de Magallanes and Ministerio de Educación y Ciencia (BIO2007-61745, SAF2006-03004).

4 pages, 2 figures, 1 table, 1 scheme.-- Printed version published Nov 24, 2008., Supporting information (NMR spectra of gomerone, 13 pages) available at: http://dx.doi.org/10.1016/j.tet.2008.09.027, The structures and relative sterochemistry of three halogenated sesquiterpenoids gomerones A–C, 1–3, isolated from Laurencia majuscula are described. They are representative of a novel carbon skeleton, gomerane, biogenetically derived from cyclization of a β-chamigrene precursor. A biogenetic relationship with related sesquiterpenoids from lower terrestrial plants Hepaticae of genera Bazzania, Mannia, Mylia, and Rebouli as well as higher plants of genera Cupressus and Juniperus has been established., This work was supported by the Ministerio de Educación y Ciencia (BIO2007-61745, SAF2006-03004) and DGUI Gobierno de Canarias (PIO42005, PUB2005/030).

6 pages, 5 tables, 2 schemes.-- Printed version published Sep 10, 2007.-- Supporting information (19 pages) available at: http://dx.doi.org/10.1016/j.tet.2007.06.080, The furanocembranolides 1–3 along with the known compounds pukalide, pukalidealdehyde, epoxypukalide, and leptolide were isolated from Leptogorgia spp. and their structures were determined by spectroscopic evidences. An NMR-based method using Pirkle's reagent at low temperature allowed us to determine the absolute configuration at C-10 of a γ-butenolide unit embedded in a flexible furanocembranolide network. The C-18 of furanocembranolides undergoes an oxidation cascade leading from a methyl group to a carboxylic acid/ester that appears to be genus specific. We introduce the concept genus-specific oxidation, a feature that provides a chemotaxonomical marker for several genera of octocorals. This concept also allowed us to propose a biogenetic pathway for these compounds., This work was supported by the MEC (BIO2007-61745, SAF2006-03004) and the DGUI Gobierno de Canarias (PI042005/003, PUB2005/030).

Compounds with three characteristic skeletons of members of the family Bonnemaisoneaceae were found to coexist in the alga Delisea fimbriata. The two new acetates 1 and 2a were also isolated; this is the first isolation of acetates from this genus. The structures, chemical transformation, and biogenetic significance of 1 and 2a are described.

3 pages, 1 figure, 2 tables.-- PMID: 16309323 [PubMed].-- Printed version published Nov 28, 2005., Three new chamigrenes, compound 1, acetyldeschloroelatol 2 (2-bromo-1,1,9-trimethyl-5-methylenespiro[5.5]undec-8-en-3-yl acetate), and acetylelatol 4 (2-bromo-8-chloro-1,1,9-trimethyl-5-methylenespiro[5.5]undec-8-en-3-yl acetate), and the known metabolites deschloroelatol 3, elatol 5, 8-acetylcaespitol 6, and caespitol 7 have been isolated from the sea hare Aplysia dactylomela. The structures of 1, 2, and 4 were determined on the basis of spectroscopic evidences. The in vitro cytotoxicity of six of these compounds against two cancer cell lines (HeLa and Hep-2) and nontumoral Vero cells was evaluated. The results support the hypothesis that the acetate derivatives decrease the toxicity of the corresponding alcohols in a strategy to store toxic metabolites acquired through the diet., This work was supported by the DGUI Gobierno de Canarias (PI2002/044), the Ministerio de Educación y Ciencia (PPQ2002-02494, REN2002-10485-E/ANT), and DGES (BQU2003-09558-CO2-01).

4 pages, 2 figures, 2 tables.-- Printed version published May 31, 2004., Two novel monoterpenes, 1 and 2, containing an unusual 1,2-bromochloro vinylic portion, were analyzed to study the influence of γ-substituents on the C-1 and H-1 chemical shifts of the 1,2-dihalo vinylic residue. This study reinforces the validity of the empirical rules based on 13C and 1H NMR spectroscopy as a helpful tool for determining the regio- and stereochemistry of substituted vicinal vinyl dihalides., This work was supported by the Ministerio de Ciencia y Tecnología (MCYT) projects REN2002-10485-E/ANT and PPQ2002-02494; DGUI of Canary Islands Government project PI2002/044 and by the Instituto Antártico Chileno (INACH).

6 pages, 1 figure, 2 tables, 1 scheme.-- Available online Dec 30, 2003., New degraded and rearranged diterpenoids, 5–8, have been isolated from the Antarctic sponge Dendrilla membranosa. The structure and relative stereochemistry of these compounds were determined by spectroscopic data. The absolute stereochemistry of 5 was determined by spectroscopic data using a chiral reagent. Conformational studies allowed us to assign also the absolute stereochemistry of 6–8, as well as those previously isolated spongian-derived metabolites with known relative stereochemistries., This work was supported by Ministerio de Ciencia y Tecnología (MCYT, projects: REN2002-10485-E/ANT and PPQ2002-02494), Instituto Antártico Chileno (INACH), and DGUI (Gobierno de Canarias: PI2002/044). A.R.D.-M. acknowledges an I3P grant from the CSIC and E.D. acknowledges a fellowship (FPI) from the CICYT.

4 pages, 2 figures, 1 table.-- Available online Dec 19, 2003., Two unique chloro-pregnane steroids have been isolated from the eastern Pacific octocoral Carijoa multiflora and their structures and stereochemistries were determined on the basis of spectral studies and molecular mechanics calculations., This work was supported by MCYT (PPQ2002-02494), DGUI of Canary Islands Government (PI2002/044) and DID project CSMAR 02/6-2 of the Universidad de Chile.

4 pages, 1 figure, 1 table.-- Printed version published Oct 14, 2002., Three new halogenated monoterpenes, 1–3, have been isolated from Plocamium cartilagineum. The structure and relative stereochemistry of these compounds were determined by spectroscopic data. Also the relative stereochemistry at C-7 for furoplocamioids A–C has been assigned., This work was supported by the Comisión Interministerial de Ciencia y Tecnología (CICYT), FEDER, MCYT (project PPQ2002-02494), Subdirección General de Cooperación Internacional and the Cooperation Programme between the Consejo Superior de Investigaciones Científicas (CSIC, Spain)-Universidad de Chile. A. R. D.-M. acknowledges a fellowship from the CICYT.

4 pages, 1 figure, 1 table, 1 scheme.-- Printed version published Mar 17, 2003., The stereochemistry at C-3 of the known compounds atomaric acid 2a, 5'a-desmethyl-5'-acetylatomaric acid 4a, and stypoquinonic acid 5a is revised to 2, 4, and 5 on the basis of a careful study of 2D NOESY experiments and also from comparison of their 1H and 13C chemical shifts with those of the related metabolites 6 and 7 isolated from Stypopodium zonale. Compound 7 is a novel unusually functionalized 1-keto-5'a-desmethyl atomaric acid derivative whose structure and stereochemistry were determined by spectroscopic means., This work was supported by the Ministerio de Ciencia y Tecnología PPQ2002-02494, FEDER and Dirección General de Universidades del Gobierno de Canarias PI2002/044. We are grateful to Professor J. Afonso-Carrillo (University of La Laguna) for the taxonomic classification of the alga. E. D. acknowledges a fellowship (FPI) from the CICYT. M. C. and A. R. D.- M. acknowledge an I3P grant from the CSIC.

5 pages, 2 figures, 1 table.-- Printed version published Jun 23, 2003., Four new labdane diterpenes, 1-4, with an unusual oxidation pattern have been isolated from the marine pulmonate Trimusculus peruvianus. The structure and stereochemistry of these compounds were determined by spectroscopic data and chemical transformations. The absolute stereochemistry of 4 was assigned by application of the modified Mosher method. These compounds exhibit in vitro moderate cytotoxic activity against human colon carcinoma cell lines., This work was supported by the Ministerio de Ciencia y Tecnología (MCYT), project ref: PPQ2002-02494, DGUI of the Canary Islands Government PI2002/044, DID project CSMAR 02/6-2 of the Universidad de Chile, Cooperation Programme between CSIC (Spain)–CONICYT (Chile), and DI of the Universidad de Antofagasta. We are grateful to BIOMAR, S.A. for performing the bioassays. A. R. D.-M. acknowledges an I3P grant from the CSIC and E. D. an FPI grant from the MCYT.

4 pages, 2 figures, 1 table.-- PMID: 12444716 [PubMed].-- Printed version published Nov 22, 2002., Three new terpenoids, 1a−3a, and the known metabolites atomaric acid, stypoquinonic acid, and 5'a-desmethyl-5'-acetylatomaric acid have been isolated from the tropical brown alga Stypopodium zonale. The structures and relative stereochemistry of the methyl ester of 1a−3a were determined by spectral methods. The methyl ester of 3a exhibits in vitro cytotoxic activity against human lung and colon carcinoma., This work was supported by the Comisión Interministerial de Ciencia y Tecnología (CICYT) and FEDER. E.D. acknowledges a fellowship (FPI) from the CICYT. We are grateful to BIOMAR S.A. for the performance of the bioassays.

4 pages, 2 figures, 1 table, 1 scheme.-- Printed version published Dec 9, 2002., A new diterpenoid of mixed biogenesis, stypolactone 8, containing a tricyclic terpenoid moiety which in combination with its spirolactone ring, leads to a novel carbon skeleton, has been isolated from the brown alga Stypopodium zonale. It's structure and relative stereochemistry were established by spectroscopic evidence and biogenetic considerations., The structure, stereochemistry and possible biogenesis for stypolactone 8 are described., This work was supported by the MCYT (project PPQ2002-02494) and DGU (Gobierno de Canarias). We are grateful to BIOMAR S. A. for performing the bioassays and to Professor J. Afonso-Carrillo (University of La Laguna) for the taxonomic classification of the alga. E.D. acknowledges a fellowship (FPI) from the CICYT. M.C. and A.R.D.-M. acknowledge an I3P grant from the CSIC.

5 pages, 1 figure, 4 tables, 1 scheme.-- PMID: 11908973 [PubMed].-- Printed version published Mar 22, 2002., Six new prenylated bromohydroquinones, 3'-methoxy-7-hydroxycymopol (1), 3-hydroxycymopolone (2), 3,7-dihydroxycymopolone (3), 7-hydroxycymopochromanone (4), 7-hydroxycymopochromenol (5), and a related 6-hydroxy derivative of cymopochromenol (6), have been isolated from the green marine alga Cymopolia barbata. The structures of these cymopol-related metabolites were determined by spectral methods., This work was supported by the Comisión Interministerial de Ciencia y Tecnología (CICYT), FEDER (projects: ANT98-1069 and 1FD97-0348-C03-03), Subdirección General de Cooperación Internacional, and the Cooperation Programme between the Consejo Superior de Investigaciones Científicas (CSIC, Spain)-Universidad de Chile and the collaboration of CEBIMAR, Cuba. E.D. acknowledges a fellowship (FPI) from the CICYT.

Three new tetrahydrofuran derivatives, marine monoterpenes, with an unusual chlorobromo vinyl functional group, have been isolated from the red alga Plocamium cartilagineum. The structure and relative stereochemistry of these compounds were determined on the basis of spectroscopic evidence and molecular mechanics (MM2) calculations. These compounds are related to pantofuranoids isolated from the antarctic Pantoneura plocamioides, which strongly suggests a close relationship between these species.

3 pages, 1 table.-- PMID: 9868144 [PubMed].-- Printed version published Dec 28, 1998., Four new marine monoterpenes have been isolated from two species of marine red algae, Plocamium cartilagineum and Pantoneura plocamioides. The structures and relative stereochemistry of these compounds were determined on the basis of spectroscopic evidence and suggest a relationship between P. cartilagineum and P. plocamioides., This work was supported by the Comisión Interministerial de Ciencia y Tecnología (CITYT) (ANT98-1069) and Instituto Antártico Chileno (INACH) and Subdirección General de Cooperación Internacional. M. Cueto acknowledges a fellowship from the Programa Nacional de la Antártida.

8 pages, 3 figures, 1 table., The participation of oxygen in the biogenesis of marine monoterpenes allowed us to isolate, from the Antarctic alga Pantoneura plocamioides, a variety of new monoterpenes that have a tetrahydrofuran ring. The structure and relative stereochemistry of these six compounds, pantofuranoids A-F (1–6), were established by spectroscopic methods. A biogenetic route for those compounds has also been proposed., The participation of oxygen in the biogenesis of marine monoterpenes allowed us to isolate from P. plocamioides a new structural type of monoterpenes, pantofuranoids A-F (1–6), containing a tetrahydrofuran ring., This work was supported by the Comisión Interministerial de Ciencia y Tecnologia (CITYT) (ANT94-0047) and INACH (Instituto Antártico Chileno). M. Cueto acknowledges a fellowship from the Programa Nacional de la Antártida.