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The detailed chemical investigations of the South China Sea soft corals Sinularia tumulosa and Sinularia depressa, yielded two new compounds, namely tumulosterol A (1) and 11’-hydroxy-α-tocopherylquinone (3), along with four related known ones (2, 5–7). Their structures were determined by extensive spectroscopic analysis and comparison with the spectral data previously reported in the literature. In bioassays, compound 1 displayed significant cytotoxic effects against H1975 and MDA-MB-231 cells with IC50 values of 6.0 and 6.3 µM, respectively. In addition, compound 3 exhibited interesting inhibitory effect on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells with IC50 value of 9.5 µM.

A further study on the rarely reported soft coral Sarcophyton mililatensis disclosed five new flexible cembrane-type macrocyclic diterpenes sarcomililatols C-G (1-5) and two known analogues 6 and 7. The structures and absolute configurations of natural macrocyclic compounds 1-6 were established by the extensive spectroscopic analysis, X-ray diffraction analysis, time-dependent density functional theory/electronic circular dichroism (TDDFT ECD) calculations, chemical reaction, and modified Mosher's method. In the bioassays, the macrocyclic diterpene 2 exhibited potent TNF-α inhibition (IC

Investigation of the South China Sea nudibranch Hexabranchus sanguineus from Sanya Bay afforded, in addition to three known compounds, nine new diterpenoids of the 5,19-cycloclerodane- (sanyanolides A-D), clerodane- (sanyanolide E) and subersin- (sanyanolides F-I) type. Remarkably, six diterpenoids aforementioned from H. sanguineus were also isolated from the sponge Chelonaplysilla sp. from the same water region, suggesting a trophic relationship between H. sanguineus and Chelonaplysilla sp. The structure and absolute configuration of new compounds were established by a combination of spectroscopic data, X-ray diffraction analysis and/or time-dependent density functional theory/electronic circular dichroism calculations. A plausible biogenetic relationship between these diterpenoids, along with the chemo-ecological implications of their co-occurrence in the two organisms investigated, was proposed and discussed. In in vitro bioassays, echinoclerodane A exhibited a potent inhibitory effect (IC50 = 2.81 μM) on LPS-induced inflammatory response in RAW 264.7 macrophage cells. In addition, echinoclerodane A and oculatolide showed considerable antibacterial activities with MIC values ranging from 1.0 to 8.0 μg/mL.

Two new scalarane sesterterpenes, hyrtiosins F and G (

Four new polyoxygenated cembranoids, namely sarcoboettgerol A (1), 12-epi-humilisin D (2), sarcoboettgerol B (3), and sarcoboettgerol C (4), together with one known related analogue, humilisin D (5), were isolated and characterized from the soft coral Sarcophyton boettgeri collected off Ximao island, Hainan Province, China. The structures and absolute configurations of the new compounds were determined by extensive spectroscopic data analyses, Cu kα single crystal X-ray diffraction analysis, and TDDFT-ECD calculations. A plausible biogenetic relationship of 3 and 4 was proposed.

The chemical investigation of the South China Sea soft coral Sinularia humilis has resulted in the isolation of a library of diverse diterpenoids, including four new cembranoids, namely, humilisins A-D (1-4), two new uncommon diterpenoids possessing a tetradecahydrocyclopenta[3',4']cyclobuta[1',2':4,5]cyclonona[1,2-b]oxirene ring system, namely, humilisins E and F (5 and 6), and eight known related compounds (7-14). Humilisin A (1) is the first cembranoid with an ether linkage between C-3 and C-7. The structures and absolute configurations of 1-8 were determined by extensive spectroscopic data analyses, chemical reactions, and a series of quantum chemical calculations including quantum mechanical-nuclear magnetic resonance (QM-NMR), time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD), and optical rotatory dispersion (ORD) methods. In bioassay, compound 6 displayed anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells.

Two new scalarane sesterterpenes, hyrtiosins F and G (1 and 2), along with two known related compounds, hyrtiosin D and sesterstatin 6 (3 and 4), were isolated from the Hainan marine sponge Hyrtios erecta. The structures of new compounds 1 and 2 were determined by detailed analysis of 1D and 2D NMR spectra and by comparison of the spectroscopic data with those reported in the literatures.

Three new diterpenoids with an unusual capnosane skeleton named lobophytrols A-C (1-3) were isolated from the South China Sea soft coral Lobophytum sp. along with one known related diterpene, (11S,12S,1E,3E,7E)-11,12-epoxycembra-1,3,7-triene (7). Their structures were elucidated on the basis of spectroscopic analysis and by comparison with those reported in the literature.

Marine sponges of the genus Stelletta are well known as rich sources of diverse and complex biologically relevant natural products, including alkaloids, terpenoids, peptides, lipids, and steroids. Some of these metabolites, with novel structures and promising biological activities, have attracted a lot of attention from chemists seeking to perform their total synthesis in parallel to intensive biological studies towards new drug leads. In this review, we summarized the distribution of the chemically investigated Stelletta sponges, the isolation, synthesis and biological activities of their secondary metabolites, covering the literature from 1982 to early 2018., Graphical abstract Marine sponges of the genus Stelletta are well known as rich sources of diverse and complex natural products with novel structures and broad biological activities, which have attracted a lot of attention from chemists seeking to perform their total synthesis in parallel to intensive biological studies towards new drug leads. In this review, we summarize the chemical and biological aspects of Stelletta sponges as promising drug sources.fx1

A new brominated polyacetylene xestonariene J (1), bearing a rare 2,4-dibromo-1-ene-3-yne terminal in the molecule, along with two known related analogues (2 and 3), was obtained from Chinese marine sponge Xestospongia testudinaria. Its structure was determined on the basis of detailed spectroscopic analysis and comparison with literature data.

Different chemotypes of Sinularia flexibilis exist in the Hainan island. Thus, a collection of this soft coral from a location different from the one of our previous study afforded three novel cembranoid esters featuring a n-butyl alcohol moiety, a structural element rare in natural products of both terrestrial and marine origin. The structures of the new compounds were elucidated by detailed spectroscopic analysis and by the comparison of their spectroscopic data with those reported in the literature. In addition, the absolute stereochemistry of the previously reported diepoxycembrene (9) was first time determined by the X-ray diffraction analysis. In bioassays, compounds 6-8 exhibited strong anti-inflammatory effect with IC values of 2.7, 4.7, and 4.2 μM, respectively, whereas compound 5 displayed cytotoxicity against several cancer cells with IC values ranging from 8.9 to 27.4 μM. A preliminary structural-activity relationship (SAR) was also described.

The chemical investigation of the South China Sea soft coral

Seven new cembrane-type diterpenes, lobophytolins C–I (3–9), and one new prenylated-guiane-type diterpene, lobophytolin J (10), along with six known related ones (1, 2, 11–14), have been isolated from the soft coral Lobophytum sp. collected off the Xisha Island in the South China Sea. Their structures were elucidated by extensive spectroscopic analysis and quantum mechanical (QM)-NMR methods. The absolute configuration of lobophytolin H (8) was determined by the application of the modified Mosher’s method and chemical transformation. Lobophytolin D (4) exhibited promising cytotoxicities in in vitro bioassays against HT-29, Capan-1, A549, and SNU-398 human cancer cell lines with IC50 values of 4.52, 6.62, 5.17, and 6.15 μM, respectively., This work was financially supported by the Natural Science Foundation of China (Nos. 81991521, 81520108028, 21672230), the National Key Research and Development Program of China (No. 2018YFC0310903), the Drug Innovation Major Project (No. 2018ZX09711-001-001-009), the SKLDR/ SIMM Project (No. SIMM1903ZZ-04) and the Spanish Ministry of Science and Innovation (PID2019-109476RB-C21). A.H.D thanks the CSIC for a JAE-intro grant to C.C.G. This study made use of the SGAI-CSIC supercomputing facilities.

Two new macrocyclic cembranoids were isolated from the South China Sea soft coral

Two new macrocyclic cembranoids were isolated from the South China Sea soft coral Lobophytum sp. Quantum mechanical–nuclear magnetic resonance (QM–NMR) methods were decisive in their structural elucidation. Better performance in arriving at definitive structures was obtained by QM–NMR methods upon incorporation of 3JHH values. The validity of this approach also supported an alternative conformational proposal versus that obtained by X-ray crystallography., We thank a reviewer for suggesting the comparative using the Xray structures. This research work was financially supported by the Natural Science Foundation of China (No. 81991521), the Drug Innovation Major Project (No. 2018ZX09711-001-001- 009). A.H.D thanks the CSIC for a JAE-intro grant to C.C.G. This study made use of the SGAI-CSIC supercomputing facilities. We thank M.H. Dorta for help with graphics edition and G. Jones, funded by Cabildo de Tenerife, TFinnova Programme supported by MEDI and FDCAN for English edition.

Two novel steroidal derivatives, erectsterates A (1) and B (2), a pair of epimers at C-10, were isolated from the South China Sea soft coral Sinularia erecta. Their structures were established by extensive spectroscopic analysis and deduction from biosynthesis route. Compounds 1 and 2 are rare steroids with a highly degradation in ring B and an ester linkage between A and C/D rings, similar with the known compounds chaxines B (3) and D from an edible mushroom Agrocybe chaxingu. To the best of our knowledge, this is the first report of such kind of steroid from soft coral. And a different biosynthetic route from the reported approach of chaxines was proposed in this paper. Interestingly, the ring C of 1 and 2 was formally oxidized by Baeyer-Villiger reaction to provide an unprecedented seven-membered lactone moiety in ring C of steroid. The in vitro anti-proliferative activities of 2 were evaluated against A549, HT-29, SNU-398 and Capan-1 cell lines. The results indicated that it showed weak cytotoxicity against the tested four cell lines.

Eleven new cembrane diterpenes, namely, sarcoehrenins A-J (1-9, 11) and (2S,11S,12S)-isosarcophytoxide (10), along with six known compounds, gibberosene B (12), (13S)-cembra-1,3,7,11-tetraen-13-ol (13), (+)-sarcophtol (14), cembrene-C (15), (1R,4R,2E,7E,11E)-cembra-2,7,11-trien-4-ol (16) and (1S,4R,2E,7E,11E)-cembratrien-4-ol (17) were isolated from the soft coral Sarcophyton ehrenbergi collected from Weizhou Island, Beibu Gulf, South China Sea. The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. The absolute configuration of compound 2 was established by the modified Mosher's method in association with TDDFT ECD calculation, while the absolute configuration of compound 3 was assigned by TDDFT ECD approach. In in vitro bioassays, compounds 13 and 17 showed potent TNF-α inhibitory activities being similar to that of positive control dexamethasone. A preliminary structural-activity relationship was also described.

A new bis-gamma-pyrone polypropionate, 4,16-di-epi-onchidiol (1), along with three known related compounds (2-4) were isolated from the marine pulmonate mollusk Onchidium sp. The structure of compound 1 was elucidated by extensive spectroscopic analysis and by comparison the NMR data with its stereoisomers 2-4, whereas its absolute configuration was determined by the combination of X-ray diffraction analysis and TDDFT-ECD calculation. In bioassay, the isolated compounds exhibited broad cytotoxicity against several cancer cell lines with IC50 values ranging from 24.6 to 88.5?M.

Two new steroids, ximaosteroid E (1) and ximaosteroid F (2), along with two known related compounds (3 and 4), were isolated from the Chinese soft coral Sinularia sp. Notably, 1 possesses an uncommon dihydrofuran group. Their structures were established from extensive spectroscopic analyses and comparisons of their spectral data with those reported in the literature. The absolute configuration of 2 was determined by applying the modified Mosher’s method. In bioassay, compounds 1, 2, and 4 showed significant cytotoxicity against the HL-60 tumor cell line with IC50 values of 1.79, 4.03 and 0.69 μM, respectively.

3-Nor-spongiolide A (1), belonging to the extremely rare 3-nor-spongian carbon skeleton, and spongiolides A (2) and B (3), having γ-butenolide instead of furan ring as usual for ring D, together with six related known metabolites were isolated from South China Sea sponge Spongia officinalis as its metabolic components. Their structures were elucidated on the basis of extensive spectroscopic analysis. The absolute configurations of three new compounds 1–3 were determined by ECD calculations.

A series of highly oxidative new cembranoids with diverse structural features such as a dienoate moiety (sarcophytonolides S – U, 1–3) or an α,β-unsaturated e-lactone (sartrolides H – J, 4–6) were obtained from Hainan soft coral Sarcophyton trocheliophorum, along with known related analogues 7–13. It is an extremely challenging work to determine the absolute configurations of these metabolites. For compounds 1, 3 and 4, solution TDDFT calculation of ECD and specific rotation were applied in combination with conformational analysis and NMR data to determine their relative and absolute configurations, leading to the revision of relative configuration of 14. The absolute configurations of compounds 8–10 were determined by the solid-state TDDFT-ECD approach, and that of 8 was further confirmed by single-crystal X-ray diffraction experiment with Cu Kα radiation. In the bioassays, compound 8 exhibited not only moderate protein tyrosine phosphatase 1B (PTP1B) inhibitory activity (IC50 = 15.4 μM) but also moderate antibacterial activity against Staphylococcus aureus Newman strain (MIC50 = 250 μM).

Ten stigmastane-type steroids bearing unusual Δ28-24-hydroxy side chains, dictyopterisins A–J, including three pairs of C-24 epimers, dictyopterisins B/C, F/G, and I/J, were isolated from the brown alga Dictyopteris undulata Holmes, together with two previously reported analogues, (24S)- and (24R)-saringosterol. Their structures were elucidated on the basis of extensive spectroscopic analysis, with their absolute configurations at the stereogenic center C-24 of the side chain being assigned by a direct comparison of 1H NMR data with those of related known compounds. The absolute configurations of the steroidal nuclei of dictyopterisins A, B, and H were determined using the modified Mosher's method. The mixture of dictyopterisins D and E and dictyopterisin I exhibited promising PTP1B inhibitory activities with IC50 values of 1.88 and 3.47 μM, respectively, comparable to the positive control oleanolic acid (IC50, 2.78 μM). In addition, the mixture of dictyopterisins D and E and dictyopterisins F–J displayed significant cytotoxicities against the human cancer cell lines HL-60 (IC50 from 1.02 to 2.70 μM) and A-549 (IC50 from 1.35 to 2.85 μM).

Five new uncommon cembranoids, named lobophycrasins A–D (1 and 3–5) and (−)-humilisin A (2), together with a known related one (6), have been isolated from Hainan soft coral Lobophytum crassum. Their structures were elucidated by extensive spectroscopic analysis, NMR calculation with DP4+ probability analysis, TDDFT-ECD (time-dependent density functional theory-electronic circular dichroism) calculations and comparison with the reported data. Further, with the aid of X-ray diffraction analysis, the structure of lobocrasol (6), which was announced possessing novel unprecedented skeleton, was firmly revised as 6a. In addition, a plausible biogenetic connection among these isolates was also proposed.

Two new cembranoids, ximaosarcophytols A (1) and B (2), together with three related known ones (3-5), were isolated from the soft coral Sarcophyton trocheliophorum collected off the Ximao Island, Hainan Province, China. Their structures including the absolute configurations were elucidated by extensive spectroscopic analysis, TDDFT/ECD (time-dependent density functional theory/electronic circular dichroism) calculations and comparison with the reported data.

Two pairs of rare naturally occurring racemic lipids, (±)-4,7-dihydroxy-4-methyl-2,5-heptanedione (1), and (±)-7-butoxy-4-hydroxy-4-methyl-2,5-heptanedione (2) were isolated from the red alga Chondria crassicaulis Harv. The structures of the racemic mixtures of 1 and 2 were elucidated by detailed spectroscopic techniques, including 1D and 2D NMR (1H and 13C NMR, 1H–1H COSY, HSQC, and HMBC) as well as mass spectrometry and optical rotation experiments, and by comparison with data for related known analogs. This is the first report of naturally occurring 4-hydroxy-4-methyl-2,5-heptanedione derivatives. Antifungal, PTP1B inhibitory, and receptor tyrosine kinase inhibitory activities of these two compounds were investigated. The results showed that compounds 1 and 2 exhibited good selective inhibition against RET tyrosine kinase activity with IC50 values of 9.56 and 8.93 μM, respectively. Compound 1 also displayed moderate antifungal activity against Cryptococcus neoformans (32609), showing a MIC80 va...

The present study was designed to develop a concise synthetic route for macrolide, with the purpose of confirming the absolute configuration of natural dihydroresorcylide (1) and making it more easily accessible for biological evaluation. The absolute configuration of C-3 in natural 1 was revised to be R by comparison of the rotation sign of synthetic (R)- and (S)-1. The synthetic (R)-1 was found to be a novel highly specific PTP1B inhibitor with an IC50 value of 17.06 μM.

One new dolabellane-type diterpenoid, named clavirolide G (1), and one known related analogue (3), have been isolated from the soft coral Clavularia viridis collected off the Xisha Islands in the South China Sea. Its structure and absolute configuration were determined on the basis of spectroscopic analysis, electronic circular dichroism, and compared with literature model compounds. The cytotoxic activity of these two compounds was evaluated against a panel of human tumor cell lines. Compound 1 showed moderate cytotoxic activity against KB and HL-60 cells.

Three new oxygenated steroids, sinulasterols A–C (1–3), along with seven known related steroids 4–10, were isolated from the Chinese soft coral Sinularia depressa. The structures of the new compounds were established from extensive spectroscopic data analyses and by comparison of their spectral data with those reported in the literature. Among the new compounds, metabolites 1 and 2 featured on unusual C-18 oxygenated pattern. In the TNF-α bioassay, compound 4 exhibited a potent inhibitory activity (IC50 = 12.1 μM), which was analogous to the positive control dexamethasone (IC50 = 8.7 μM), metabolites 1 and 2 displayed a moderate inhibitory activity (IC50 51.1 μM and 22.7 μM respectively).

A detailed chemical investigation of the nudibranch Glossodoris atromarginata collected from Weizhou Island, South China Sea, yielded a new spongian-type diterpene 1, together with the four known-related compounds 2-5. The structure of the new compound 1 was elucidated by the detailed spectroscopic analysis, the comparison of the spectroscopic data with the known diterpene isoagatholactone, and the 13 C chemical shift calculation. In addition, evidence for the absolute stereochemistry of the known compound 2 was, for the first time, provided by the application of time-dependent density functional theory electronic circular dichroism calculation.

Four new cembranoids (1–4) were isolated from the extracts of a soft coral collected from the sea area near Xisha Island, South China Sea. The structures of these compounds were determined mainly by spectroscopic analyses, with the absolute configuration of 1 being established by X-ray diffraction analysis. In bioassay, compounds 1 and 3 displayed moderate inhibitory activity against Aβ42 aggregation (20.6% and 37.2% inhibition at 10 μM). The binding mode of 1 with Aβ42 monomer was predicted by molecular docking. In addition, compounds 1 and 3 did not show cytotoxicity against human tumor cell lines (SH-SY5Y, MDA-MB-426, A549, Hep3B, and HT-29) at 100 μM. Taken together, these cembranoids as new anti-Aβ aggregation agents derived from Sinularia sp. provided a new chemical scaffold for anti-Alzhemer's disease drug discovery.

A new bis-γ-pyrone polypropionate, 4,16-di