C15 Acetogenin Research Articles

Secondary Metabolites with Anti-Inflammatory Activity from Laurencia majuscula Collected in the Red Sea.

The chemical investigation of the organic extract of the red alga Laurencia majuscula collected from Hurghada reef in the Red Sea resulted in the isolation of five C15 acetogenins, including four tricyclic ones of the maneonene type (1-4) and a 5-membered one (5), 15 sesquiterpenes, including seven lauranes (6-12), one cuparane (13), one seco-laurane (14), one snyderane (15), two chamigranes (16, 17), two rearranged chamigranes (18, 19) and one aristolane (20), as well as a tricyclic diterpene (21) and a chlorinated fatty acid derivative (22). Among them, compounds 1-3, 5, 7, 8, 10, 11 and 14 are new natural products. The structures and the relative configurations of the isolated natural products have been established based on extensive analysis of their NMR and MS data, while the absolute configuration of maneonenes F (1) and G (2) was determined on the basis of single-crystal X-ray diffraction analysis. The anti-inflammatory activity of compounds 1, 2, 4-8, 10, 12-16, 18 and 20-22 was evaluated by measuring suppression of nitric oxide (NO) release in TLR4-activated RAW 264.7 macrophages in culture. All compounds, except 6, exhibited significant anti-inflammatory activity. Among them, metabolites 1, 4 and 18 did not exhibit any cytostatic activity at the tested concentrations. The most prominent anti-inflammatory activity, accompanied by absence of cytostatic activity at the same concentration, was exerted by compounds 5 and 18, with IC50 values of 3.69 μM and 3.55 μΜ, respectively.

A new isomaneonene derivative from the red alga Laurencia cf. mariannensis

Determining the structures of new natural products from marine species not only enriches our understanding of the diverse chemistry of these species, but can also lead to the discovery of compounds with novel and/or important biological activities. Herein, we describe the isolation of isomaneonene C (1), a new halogenated C15 acetogenin, and three known compounds, α-snyderol (2), cis-maneonene D (3), and isomaneonene B (4), from the organic extract obtained from the red alga Laurencia cf. mariannensis collected from Iheya Island, Okinawa, Japan. The structures of these secondary metabolites were elucidated spectroscopically. All compounds were inactive at 30 μg/disc against methicillin-resistant Staphylococcus aureus (MRSA) in combination treatment with a β-lactam drug, meropenem.

New halogenated C15 acetogenins from Okinawan sea hare Aplysia dactylomela

Two new C15 acetogenins 1 and 2, along with four known sesquiterpenes isolaurenisol (3), laurokamurene D (4), itomanol (5), and acetylelatol (6), were isolated from sea hare Aplysia dactylomela. The structures, including the relative stereochemistries, of 1 and 2 were determined based on spectroscopic evidence. Finally, the in vitro cytotoxicities of the six compounds against S1T cells, an adult T-cell leukemia cell line, were evaluated.

New C15 Acetogenins from Two Species of Laurencia from the Aegean Sea.

The chemical diversity of the approximately 1,200 natural products isolated from red algae of the genus Laurencia, in combination with the wide range of their biological activities, have placed species of Laurencia in the spotlight of marine chemists’ attention for over 60 years. The chemical investigation of the organic (CH2Cl2/MeOH) extracts of Laurencia microcladia and Laurencia obtusa, both collected off the coasts of Tinos island in the Aegean Sea, resulted in the isolation of 32 secondary metabolites, including 23 C15 acetogenins (1–23), 7 sesquiterpenes (24–30) and 2 diterpenes (31 and 32). Among them, six new C15 acetogenins, namely 10-acetyl-sagonenyne (2), cis-sagonenyne (3), trans-thuwalenyne C (4), tinosallene A (11), tinosallene B (12) and obtusallene XI (17), were identified and their structures were elucidated by extensive analysis of their spectroscopic data. Compounds 1–3, 5–11, 13 and 15–32 were evaluated for their antibacterial activity against Staphylococcus aureus and Escherichia coli.

Unified Approach for the Total Synthesis of Bis-THF C15 Acetogenins: A Chloroenyne from Laurencia majuscula, Laurendecumenyne B and Laurefurenynes A/B

AbstractA highly diastereoselective total synthesis of several bis-THF C15 acetogenin natural products, chloroenyne from Laurencia majuscula, laurendecumenyne B, and laurefurenynes A/B, is reported. Additionally the synthesis of an advanced intermediate reported in the earlier total synthesis of (E/Z)-elatenynes (formal synthesis) is described. The salient features in the synthesis include epoxide opening, Birch reduction, Sharpless asymmetric dihydroxylation-cycloetherification, SN2 halo­genation, and a relay cross metathesis.

Antiproliferative Activity of Mycalin A and Its Analogues on Human Skin Melanoma and Human Cervical Cancer Cells.

Mycalin A, a polybrominated C15 acetogenin isolated from the encrusting sponge Mycale rotalis, displays an antiproliferative activity on human melanoma (A375) and cervical adenocarcinoma (HeLa) cells and induces cell death by an apoptotic mechanism. Various analogues and degraded derivatives of the natural substance have been prepared. A modification of the left-hand part of the molecule generates the most active substances. A structurally simplified lactone derivative of mycalin A, lacking the C1–C3 side chain, is the most active among the synthesized compounds exhibiting a strong cytotoxicity on both A375 and HeLa cells but not but not on human dermal fibroblast (HDF) used as healthy cells. Further evidence on a recently discovered chlorochromateperiodate-catalyzed process, used to oxidise mycalin A, have been collected.

Thuwalallenes A-E and Thuwalenynes A-C: New C15 Acetogenins with Anti-Inflammatory Activity from a Saudi Arabian Red Sea Laurencia sp.

Thuwalallenes A–E (1–3, 5 and 8) and thuwalenynes A–C (4, 6, 7), new C15 acetogenins featuring uncommon ring systems, along with cis-maneonene D (9), thyrsiferol (10) and 23-acetyl-thyrsiferol (11) were isolated from the organic extract of a population of the red alga Laurencia sp., collected at Rose Reef off the village of Thuwal in the Red Sea waters of the Kingdom of Saudi Arabia. The structure elucidation of the isolated natural products was based on extensive analysis of their spectroscopic data. Compounds 1–6, 8, 10 and 11 were evaluated for their anti-inflammatory activity by quantifying nitric oxide (NO) release in response to TLR4 stimulation in macrophages. Besides compound 4 that did not exhibit any activity, all other tested metabolites inhibited NO production from activated macrophages. Among them, thyrsiferol (10) and 23-acetylthyrsiferol (11) displayed activity with IC50 values in the low nM scale without cytotoxicity.

Vagiallene, a Rearranged C15 Acetogenin from Laurencia obtusa.

Vagiallene (1), a rearranged C15 acetogenin with a molecular formula and a carbon skeleton unprecedented in natural products, was isolated as a trace constituent from the organic extract of the red alga Laurencia obtusa from Lefkada island. The planar structure and the relative configuration of 1 were established on the basis of extensive analysis of its spectroscopic data, while its absolute configuration was determined by comparison of its experimental and quantum-mechanically predicted electronic circular dichroism spectra.

New bioactive C15 acetogenins from the red alga Laurencia obtusa

Background and Objective: With regard to the uniqueness of the red algae of the genus Laurencia as the source of C15-acetogenins, along with the diversity of biological applications; the acetogenin content of the Red Sea Laurencia obtusa was investigated. Materials and Methods: Fractionation and purification of the CH2Cl2/MeOH extract were carried out by applying several chromatographic techniques, including column and preparative thin-layer chromatography; followed by a series of 1H nuclear magnetic resonance measurements to give rise of some interesting notes. Toxicity to Artemia salina was evaluated. The apoptosis induced by these two compounds was demonstrated by DNA fragmentation assay and microscopic observation. Results: A new rare chloroallene-based C15 acetogenin, laurentusenin (1) along with a new furan ring containing C15 acetogenin, laurenfuresenin (2), were isolated from the red alga L. obtusa. Comparing 1D and 2D NMR, MS, ultraviolet and infrared radiation spectral data for the newly isolated compounds with the reported bromoallene containing acetogenins spectral data was played the crucial role for characterization of their chemical structures. 1 and 2 exhibited bare toxicity (LD50 >12 mM) in test organism, A. salina and induced apoptotic death confirmed by DNA fragmentation and microscopic investigations. Conclusion: The isolated metabolite 1 showed unusual substituted allene side chain, while 2 inserted furan ring as a new acetogenin nucleus. Both compounds may play a role in apoptosis induction and initiation and propagation of inflammatory responses. Abbreviations used: NMR: Nuclear magnetic resonance; MS: Mass spectrometry; UV: Ultraviolet spectroscopy; IR: infrared radiation; EIMS: Electron ionization mass spectra; TLC: Thin-layer chromatography; PPP: Platelet poor plasma; PRPDS: platelet-rich plasma derived serum. DEPT: Destortionless Enhancement by Polarization Transfer; NOESY: Nuclear Overhauser Effect Spectroscopy; HSQC: Heteronuclear Single Quantum Coherence; HMBC: Heteronuclear Multiple-quantum Correlation; 1H-1H COSY: Correlation Spectroscopy.

Correction to Halogenated C15 Acetogenin Analogues of Obtusallene III from a Laurenciella sp. Collected in Corsica.

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to Halogenated C15 Acetogenin Analogues of Obtusallene III from a Laurenciella sp. Collected in CorsicaSylvain Sutour*Sylvain SutourMore by Sylvain Sutourhttp://orcid.org/0000-0001-9676-7123, Bruno TherrienBruno TherrienMore by Bruno Therrienhttp://orcid.org/0000-0002-0388-2745, Stephan H. von ReussStephan H. von ReussMore by Stephan H. von Reusshttp://orcid.org/0000-0003-4325-5495, and Félix TomiFélix TomiMore by Félix TomiCite this: J. Nat. Prod. 2018, 81, 10, 2306Publication Date (Web):September 26, 2018Publication History Published online26 September 2018Published inissue 26 October 2018https://doi.org/10.1021/acs.jnatprod.8b00784Copyright © 2018 American Chemical Society and American Society of PharmacognosyRIGHTS & PERMISSIONSArticle Views1435Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (241 KB) Get e-Alerts Get e-Alerts

Halogenated C15 Acetogenin Analogues of Obtusallene III from a Laurenciella sp. Collected in Corsica.

NMR chemical profiling of a Laurenciella sp. using a computerized method developed in our laboratory resulted in the identification of five new compounds (1-5) and 17 known compounds, among which 3-(E)-laurenyne represented by far the most abundant metabolite. Compounds 1 to 5 were isolated and fully characterized by detailed spectroscopic analysis. The absolute configuration and structural features of compound 1 were determined by single-crystal X-ray diffraction analysis. Compounds 1 to 4 are 12-membered cyclic ether acetogenins that are present in solution as interconverting conformers exhibiting an (aR) configuration of the bromoallene unit together with an S configuration at C-4. Among these, compound 3 is the first obtusallene derivative with bromine substituents at both the C-7 and C-12 positions. Compound 5 is an acetogenin bearing a [5.5.1]bicyclotridecane ring system. A plausible biosynthetic route to 1-4 is proposed.

Pinnatifidenyne-Derived Ethynyl Oxirane Acetogenins from Laurencia viridis.

Red algae of Laurencia continue to provide wide structural diversity and complexity of halogenated C15 acetogenin medium-ring ethers. Here, we described the isolation of three new C15 acetogenins (3–5), and one truncated derivative (6) from Laurencia viridis collected on the Canary Islands. These compounds are interesting variations on the pinnatifidenyne structure that included the first examples of ethynyl oxirane derivatives (3–4). The structures were elucidated by extensive study of NMR (Nuclear Magnetic Resonance) data, J-based configuration analysis and DFT (Density Functional Theory) calculations. Their antiproliferative activity against six human solid tumor cell lines was evaluated.

Construction of 6,10-syn- and -anti-2,5-Dioxabicyclo[2.2.1]heptane Skeletons via Oxonium Ion Formation/Fragmentation: Prediction of Structure of (E)-Ocellenyne by NMR Calculation.

A highly efficient and stereoselective route to potential synthetic intermediates for ocellenyne and related C15 acetogenin natural products with 6,10-syn- and 6,10-anti-2,5-dioxabicyclo[2.2.1]heptane core structures has been developed by means of an iterative biogenesis-inspired oxonium ion formation/fragmentation sequence. In accordance with chemical transformations, the most likely stereostructure for (E)-ocellenyne on the basis of GIAO 13C NMR calculations possesses a 6,10-anti-2,5-dioxabicyclo[2.2.1]heptane core, as predicted from a plausible biosynthetic pathway, instead of the spectroscopically proposed 6,10-syn-2,5-dioxabicyclo[2.2.1]heptane skeleton.

Substrate-Controlled Asymmetric Total Synthesis and Structure Revision of (-)-Bisezakyne A.

The first asymmetric total synthesis and subsequent structure revision of (-)-bisezakyne A, a Laurencia C15 acetogenin from Alpysia oculifera, has been accomplished. Our substrate-controlled synthesis of this oxolane natural product features a highly stereoselective "protecting-group-dependent" intramolecular amide enolate alkylation strategy for the synthesis of the key 9,10-trans-9,12-cis-10-hydroxytetrahydrofuran intermediate through "nonchelate" control. In addition, our synthesis determined the absolute configuration of the halogenated marine natural product.

C15 acetogenins from the Laurencia complex: 50 years of research – an overview

Acetogenins are secondary metabolites derived from the polyketide pathway and their potential role as chemotaxonomical markers for red algae belonging to the Laurencia complex has been long pointed out. C15 acetogenins from algae are quite different from plant acetogenins: they are usually halogenated, and have an enyne or a bromoallene terminal group. Since they were first reported, laurencin and other algal acetogenins have inspired great curiosity among natural product chemists and also those working with synthesis. This paper reviews the literature about C15 acetogenins, focusing on their distribution, chemical and biological aspects, including their reported biological activities.

A Brazilian sample of the red alga Laurencia nsp., yields sphingosines new to the marine environment

Marine algae belonging to the genus Laurencia are the most prolific producers of secondary metabolites compared to any other marine genus. The secondary metabolites produced by these plants are typically halogenated and have a wide variety of biological properties. The most common structural classes encountered being sesquiterpenes, diterpenes, triterpenes, sterols, C15 acetogenins and long-chain hydrocarbons. Sphingosines are among the lesser reported compounds isolated from this genus, with only one, (+)-N-(2S, 3R)-2-acetamido-3-acetoxyoctadecan-l-ol, being reported to date. In this poster presentation we report the isolation of additional sphingosines, including 1 and 2, from the genus Laurencia, this time from a new species collected in Brazil.

Chemical relationship between red algae genus Laurencia and sea hare (Aplysia dactylomela Rang) in the North Borneo Island

Red algae genus Laurencia is an interesting alga with the ability to produce halogenated secondary metabolites that exhibits ecological and pharmaceutical potential. In nature, Laurencia is selectively grazed by sea hares (Aplysia dactylomela). In this study, Laurencia populations in three islands (Mantanani, Sulug, and Dinawan Islands) in the coastal waters of North Borneo were investigated and their chemical relationship with sea hare determined. Four species of Laurencia were found to grow abundantly in these waters, Laurencia snackeyi, Laurencia majuscula, Laurencia nangii, and Laurencia similis. Sea hares, Aplysia dactylomela, found grazing on Laurencia were collected and their chemical composition determined. A total of 20 halogenated metabolites were isolated and identified via spectroscopic data. Isolated compounds could be grouped into syndrean (5), chamigrane (6), non-chamigrane sesquiterpene (3), cuparane (1), bromoindole (2), and C15 acetogenin (acetylene type) (3). Sea hares from Mantanani, Sulug, and Dinawan Islands contained a total of 9, 10, and 10 compounds, respectively. In addition, 12-acetoxypalisadin B (1), which was isolated from sea hares of Sulug Island is a first record of its existence in nature.

ChemInform Abstract: Bioactive C15 Acetogenins from the Red Alga Laurencia obtusa.

AbstractThree new C15 acetogenins (I)—(III) are isolated from the ether extract of the red alga Laurencia obtusa along with one known compound.

A General Strategy for the Stereocontrolled Preparation of Diverse 8- and 9-Membered Laurencia-Type Bromoethers

A unique procedure to effect a ring-expanding bromoetherification process is described, wherein tetrahydrofurans and tetrahydropyrans are smoothly transformed into 8- and 9-membered bromoethers in a regio- and stereocontrolled manner through the use of BDSB (bromodiethylsulfonium bromopentachloroantimonate). These products resemble the cores of the Laurencia C15 acetogenins. In light of the generality and effectiveness of the approach, this work provides a unique strategy for their laboratory preparation and may implicate a possible biosynthesis pathway.

New Larvicidal Acetogenin from the Red Alga Laurencia papillosa

AbstractA new C15 acetogenin, cyclic enyne (12E)‐cis‐maneonene‐E (1) and (12Z)‐trans‐maneonene‐B (2), together with different secondary metabolites including sesquiterpenoid 2,10‐dibromo‐3‐chloro‐α‐chamigrene (3) and fatty acid aldehydes (4–8) were isolated from the petroleum ether extract of a red alga, identified as Laurencia papillosa, collected from the Saudi Red Sea coast. The L. papillosa crude extract and its active ingredient acetogenin (1) have been evaluated for the ability to control two main economically important pests, the confused flour beetle larvae Tribolium confusum and Culex pipiens mosquito larvae. Compound 1 showed high potential as a natural insecticide against these two pests. In the case of T. confusum larvae, the LD50 values were 0.21 and 0.16% after 6 and 12 days of treatment with crude extract and acetogenin, respectively. On the other hand, the resulting LC50 values of mosquito larvae bioassay were 30.7, 36.9, and 41.8 ppm after 24 h treatment against 2nd, 3rd, and 4th larval instars, respectively. Also, an increase of the insecticidal effects against mosquito larvae was recorded after extending treatment time to 48 h.