Fragilolides A-Q,norditerpenoid and briarane diterpenoids from the gorgonian coral Junceella fragilis

Chemical investigation of the gorgonian coral Junceella fragilis resulted in the isolation of a new norditerpenoid fragilolide A (1), sixteen new briarane diterpenoids fragilolides B-Q (2–17), together with frajunolides H and N, and three known norcembranoids scabrolide D, sinuleptolide and 5-epi-sinuleptolide. The structures of new compounds were determined on the basis of extensive spectroscopic analysis, including the experimental and calculated ECD data and single-crystal X-ray diffraction for the configurational assignments. The structure of fragilolide A featured an unprecedented 4,13- and 7,11-fused tetracyclic norcembranoid, while the biogenetic relationships of the briarane analogues were postulated. Frajunolide H exerted significant inhibition against a panel of tumor cell lines, and six briarane diterpenoids (3, 6, 8, 12, 16, and frajunolide N) exhibited the inhibitory effects against the HBeAg express of hepatitis B virus in HepAD38 cells. In addition, sinuleptolide and 5-epi-sinuleptolide exerted the effects to inhibit NO production in RAW264.7 macrophage cells, in addition to the activation of ARE and the inhibition of NF-κB expression.     

New hydroperoxybriarane diterpenoids from the octocoral Briareum violaceum

A known briarane, brianthein W (1), along with four new hydroperoxybriaranes, briaviolides R–U (2–5), have been obtained from the octocoral Briareum violaceum. The absolute configuration of 1 was determined by X-ray analysis for the first time and the structures of briaranes 2–5 were established by spectroscopic methods. Bioactivity study showed that briarane 3 decreased the production of superoxide anions from human neutrophils.     

2-Acetoxybriaranes from Briareum violaceum

Five 2-acetoxybriaranes, including two known analogues, excavatolides B (1), E (2), along with three new metabolites, briaviolides V–X (3–5), have been obtained from the octocoral Briareum violaceum. The absolute configurations of 1 and 2 were determined by X-ray analysis for the first time and the structures of 3–5 were established by spectroscopic methods. Bioactivity study showed that briarane 3 decreased the release of elastase from human neutrophils.     

New metabolites with antibacterial activity from the marine angiosperm Cymodocea nodosa

Four new metabolites (1-4) have been isolated from the organic extract of the seagrass Cymodocea nodosa, collected at the coastal area of Porto Germeno, in Attica Greece. Compounds 1 and 2 belong to the structural class of diarylheptanoids, which have been found only once before in marine organisms [Kontiza, I.; Vagias, C.; Jakupovic, J.; Moreau, D.; Roussakis, C.; Roussis, V. Tetrahedron Lett.2005, 46, 2845-2847]. Compound 3 is a new meroterpenoid, while compound 4, to the best of our knowledge, is the first briarane diterpene isolated from seaweeds, and only the second analog of this class with a tricyclic skeleton. Furthermore metabolite 4 is the first brominated briarane diterpene. The structures and the relative stereochemistry of the new natural products were established by spectral data analyses. The new metabolites were submitted for evaluation of their antibacterial activity against multidrug-resistant (MDR) pathogens including methicillin-resistant (MRSA) strains of Staphylococcus aureus, as well as the rapidly growing mycobacteria, Mycobacterium phlei, Mycobacterium smegmatis, and Mycobacterium fortuitum.     

Juncenolide E,A New Briarane from Taiwanese Gorgonian Junceella Juncea

In addition to junceellolides B ( 3 ) and C ( 4 ), a new briarane, juncenolide E ( 1 ) has been isolated from the acetone extract of the red gorgonian Junceella juncea, collected on the southern coast of Taiwan. The structure of juncenolide E was determined by interpretation of MS, COSY, HMQC, HMBC and NOESY spectra.     

Four New Briarane Diterpenoids from the Gorgonian Coral Junceella fragilis

Chemical investigation of the gorgonian coral Junceella fragilis, collected by scuba diving in Taiwan, resulted in the isolation of four new briarane‐type diterpenoids, frajunolides A–D ( 1 – 4 ), along with three known briaranes. Their structures were elucidated on the basis of spectroscopic studies, especially 1‐ and 2D‐NMR as well as HR‐MS experiments. The inhibitory effect of all isolated metabolites towards superoxide‐anion generation and elastase release by human neutrophils in response to formylmethionyl‐leucyl‐phenylalanine/dihydrocytochalasin B (FMLP/CB) was evaluated.     

Junceellonoids A and B,Two New Briarane Diterpenoids from the Chinese Gorgonian Junceella fragilis Ridley

Two new diterpenoids, junceellonoids A and B ( 1 and 2 , resp.), together with the seven known diterpenoids 3 – 9 , all possessing the briarane carbon skeleton, were isolated from the gorgonian Junceella fragilis Ridley , collected in the South Sea of China. The structures and relative configurations of the new metabolites were elucidated based on extensive spectral analysis and by comparison with known spectral data.     

Excavatoids A-D, new polyoxygenated briaranes from the octocoral Briareum excavatum

Three polyoxygenated briaranes, including two new compounds, excavatoids A (1) and B (2), and a known metabolite, briaexcavatin I (3), were isolated from the cultured octocoral Briareum excavatum. Moreover, the wild type B. excavatum, collected off southern Taiwan coast, yielded two new 5,6-epoxybriaranes, excavatoids C (4) and D (5). The structures of new compounds 1, 2, 4, and 5 were determined by spectroscopic methods and the structure of 1 was further confirmed by X-ray diffraction data analysis. The X-ray structure for briaexcavatin I (3) was also reported for the first time. Excavatoid A (1) is the first briarane which possesses six hydroxy groups and a 17-methoxy group. Excavatoid C (4) is the first 12,13-secobriarane which possesses a novel pentacyclic skeleton with an ?-lactone. Excavatoid D (5) displayed moderate inhibitory effects on superoxide anion generation and elastase release by human neutrophils.     

Dichotellides A-E, five new iodine-containing briarane type diterpenoids from Dichotella gemmacea

Five new briarane type diterpenoids, dichotellides A−E (1−5), were isolated from the South China Sea gorgonian Dichotella gemmacea together with four known analogues (6−9). Compounds 1−5 represent the first examples of iodine-containing briarane type diterpenoids from nature. The structures of these diterpenoids were elucidated by spectroscopic analysis, including 1D, 2D-NMR, and HRESIMS, and the absolute configuration of 1 was further confirmed by single crystal X-ray diffraction analysis. All the isolates were evaluated for cytotoxicity activity against four human tumor cell lines, and only 3 exhibited marginal activity against SW1990 (human pancreatic cancer).     

Bis-allylic Reactivity of the Funicolides, 5,8(17)-diunsaturated briarane diterpenes of the sea pen Funiculina quadrangularis from the tuscan archipelago,leading to 16-nortaxane derivatives

Funicolides A–C ( 1–3 ), D ( 5 ), and E ( 7 ) and 7-epifunicolide A ( 4 ), new 5,8(17)-diunsaturated briarane diterpenes, as well as the known analogue brianthein W ( 6 ), were isolated from the pennatulacean coral Funiculina quadrangularis (PALLAS , 1766) collected in the Tuscan archipelago. Easy degradation under oxidative and/or basic conditions served to assign the ester groups at C(2) or C(14), while revealing bis-allylic reactivity at C(7) with formation of 16-nortaxane derivatives.     

New briaranes from the octocorals Briareum excavatum (Briareidae) and Junceella fragilis (Ellisellidae)

Six 12-hydroxybriaranes, including four new diterpenoids, briaexcavatins I-L (1-4), and two known metabolites, excavatolides C (5) and E (6), have been isolated from the cultured scleraxonia Briareum excavatum. In addition, the gorgonian coral Junceella fragilis yielded a new chlorinated briarane, fragilide C (10). The structures of above compounds were determined by spectroscopic methods and the structures of 5 and 6 were further confirmed by X-ray data analysis for the first time. The absolute configuration of 6 was elucidated by chemical conversion. Some of these briaranes have displayed inhibitory effects on superoxide anion generation by human neutrophils.     

Briarenolide E: the first 2-ketobriarane diterpenoid from an octocoral Briareum sp. (Briareidae)

A novel 2-ketobriarane diterpenoid, briarenolide E (1), was isolated from an octocoral Briareum sp. The structure of briarane 1 was elucidated by interpretations of spectral data. Compound 1 displayed modestly inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils.     

Briaexcavatins C-F, four new briarane-related diterpenoids from the Formosan octocoral Briareum excavatum (Briareidae)

Four new briarane-related diterpenoids, designated as briaexcavatins C-F (1-4), were isolated from the Formosan octocoral Briareum excavatum, collected off southern Taiwan coast. The structures of these new metabolites were elucidated by the interpretation of spectroscopic and chemical methods. The configuration of 1 was further supported by molecular mechanics calculations. Briarane 1 has been shown to exhibit mild cytotoxicity toward MDA-MB-231 human breast tumor cells and briarane 3 was found to show activity to inhibit neutrophil elastase release in humans.     

Briarenolide J,the first 12-chlorobriarane diterpenoid from an octocoral Briareum sp. (Briareidae)

A novel 6,12-dichlorobriarane diterpenoid, briarenolide J (1), was isolated from an octocoral identified as Briareum sp. The structure of briarane 1 was elucidated by spectroscopic methods. Briarenolide J (1) is the first metabolite of a briarane-related natural product found to possess a chlorine atom at C-12 and this compound was found to display inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils with IC₅₀ values of 14.98 and 9.96 μM, respectively.     

New Briaranes from the South China Sea Gorgonian Junceella fragilis

Three new briarane diterpenes, junceellonoids C–E ( 1 – 3 ), along with six known briaranes, junceellin A ( 4 ), praelolide ( 5 ), and junceellolides A‐D ( 6 – 9 ), were isolated from the EtOH/CH₂Cl₂ extracts of the South China Sea gorgonian coral Junceella fragilis. The structures of 1 – 3 were established by extensive spectroscopic analysis, including 1D‐ and 2D‐NMR data. Compounds 1 and 2 exhibited mild cytotoxicity against human galactophore carcinoma (MDA‐mB‐231 and MCF‐7) cells at the concentration of 100 μM .     

Briaexcavatins M-P, four new briarane-related diterpenoids from cultured octocoral Briareum excavatum (Briareidae)

Four new briarane-related diterpenoids, designated as briaexcavatins M-P (1-4), were isolated from the cultured octocoral Briareum excavatum. The structures, including the relative configurations of natural products 1-4 were established on the basis of extensive spectral data analysis and by comparison with the spectral data from other known metabolites featuring a briarane carbon skeleton.     

Diterpenoids from cultured Erythropodium caribaeorum

The known antimitotic agent eleutherobin and the briarane diterpenoids erythrolides A and B have been isolated from cultured specimens of Erythropodium caribaeorum in amounts comparable to those reported from wild-harvested reef animals. The novel diterpenoid aquariolide A, having an unprecedented highly rearranged carbon skeleton (named aquariane), has also been found. The aquariane skeleton can be formally derived from the briarane skeleton by sequential di-pi-methane and vinyl-cyclopropane rearrangements. [structure: see text]     

Briaexcavatolides X-Z, three new briarane-related derivatives from the gorgonian coral Briareum excavatum

Three new polyoxygenated briarane-type diterpenoids, briaexcavatolides X-Z (1-3), have been isolated from the gorgonian coral Briareum excavatum. The structures, including the relative configurations of briaranes 1-3, were elucidated by spectroscopic methods, particularly in 1D and 2D NMR experiments. The configuration of briarane 1 was further supported by molecular mechanics calculations.     

Prepatellamide A, a new cyclic peptide from the ascidianLissoclinum patella

A new cyclic peptide, prepatellamide A (1), along with three known cyclic peptides (2)— (4), was isolated from the ascidianLissoclinum patella. The structure of prepatellamide A was determined from one- and two-dimensional¹H and¹³C NMR spectra. The known cyclic peptides were identified as patellamides A (2), B (3) and C (4).     

On the Funicolides,Briaranes of the Pennatulacean Coral Funiculina quadrangularis from the Tuscan Archipelago: Conformational preferences in this class of diterpenes

Kinetic and equilibrium NMR studies of briarane diterpenes isolated from the pennatulacean coral Funiculina quadrangularis showed that funicolide A ( 1 ), funicolide D ( 5 ), and brianthein W ( 6 ), with R² = H_β, undergo slow flipping by rotation of the C(1)? C(2)? C(3)? C(4) dihedral angle, giving rise to two observable conformers in a 4:96 population ratio, both having an axial AcO? C(14) and C(16) pointing ‘downwards’, but differing for pseudoaxial or pseudoequatorial position of R¹O, respectively. δ(C) for the minor conformers could be quickly assigned by an original emulation methodology. Similar studies revealed that funicolide B ( 2 ), 7-epifunicolide A ( 4 ), funicolide E ( 7 ), and unnatural epibrianthein W ( 8 ) undergo similar motions, where, however, the nature of the α-positioned substituent R² determines which conformer predominates: axial R¹O for R² = H_β ( 4 and 8 ) or equatorial R¹O for R² α-OH, ( 2 and 7 ). In contrast, funicolide C ( 3 ) proved to undergo slow conformational motions that involve also the cyclohexene ring, resulting in two observable conformers characterized by either an equatorial AcO? C(14) and trans-diaxial C(2)/C(9) or an axial AcO? C(14) and trans-diequatorial C(2)/C(9) in a 9:1 population ratio, respectively. These observations, and molecular-mechanics calculations for briaranes known to exhibit broad NMR signals, lead to general views on the conformational preferences of diterpenes of this class.