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A novel diterpenoid, sarcomililate A (1), possessing a previously undescribed tricyclo[11.3.0.02,16]hexadecane scaffold, along with two new cembranoids, sarcomililatols A and B (2 and 3), and two known related diterpenoids (4 and 5), was isolated from the Hainan soft coral Sarcophyton mililatensis. The complete chemical structure including absolute configuration (AC) of 1 was unambiguously determined by a combination of residual dipolar coupling (RDC)-based NMR analysis, TDDFT-ECD (ECD = electronic circular dichroism) calculation, and Snatzke's method. The AC of 1 was further confirmed by a comparison with 2, whose AC was determined by anomalous X-ray diffraction. A plausible biogenetic relationship of 1-3 was further proposed. All the reported compounds exhibited interesting inhibitory effects on the ConA-induced T lymphocytes and/or lipopolysaccharide (LPS)-induced B lymphocytes proliferation.

A new 5α,8α-epidioxysterol, namely yalongsterol A (1), along with two known related steroids 5α,8α-epidioxy-24-methyl-cholesta-6,24(28)-dien-3β-ol (2) and (22E,24S)-5α,8α-epidioxy-24-methyl-cholesta-6,22-dien-3β-ol (3), were isolated from the South China Sea soft coral Sinularia sp. Their structures were established by extensive spectroscopic analyses and comparisons of the spectral data with those reported in the literature. In bioassay, compounds 1-3 showed moderate immunosuppressive activities against T and/or B lymphocyte cells with IC50 values ranging from 19.30 to 59.49 μM, and low cytotoxicity on murine splenocytes with CC50 values ranging from 40.88 to 62.29 μM.[Formula: see text].

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 fruits, twigs and leaves of Daphniphyllum oldhamii (Hemsl.) K. Rosenthal, collected from Longshan County, Hunan Province, China, were chemically investigated. Three undescribed daphniphyllum alkaloids, namely longshanoldhamines A‒C, and six known related ones have been isolated from the fruits, whereas two undescribed triterpenoids and one undescribed lignan, along with six known triterpenoids, were found in the twigs and leaves. Their structures were elucidated by extensive spectroscopic analysis, X-ray diffraction analysis and comparison with the reported data.

Eleven novel cembranoid derivatives were designed, synthesized, and evaluated for their inflammation related activities on the basis of our isolated and previously reported anti-inflammatory marine cembranoids. In bioassay, compound 11 displayed the most promising inhibitory effects with IC50 value of 1.1 μM for the TNF-α inhibitory activity. The further mechanism study of 11 on the inflammatory signaling transduction of RAW264.7 cells was also performed. This research may give an insight for the discovery of marine cembranoid derived anti-inflammatory drug leads.

Two new diterpene derivatives were obtained by semisynthesis from enzymatically generated catenul-14-en-6-ol. The EI-MS fragmentation mechanisms of three enzyme products and the two semisynthetic derivatives were investigated by extensive 13C-labelling experiments.

A further systematically chemical investigation of the South China Sea soft coral Sinularia erecta led to the discovery of two rare casbane diterpenoids with an uncommon 8,10-peroxide bridge, sinuereperoxides B (1) and C (2), five new casbanes with other oxygenated patterns (3–7), and seven known casbanes (8–14). The structures and absolute configurations of 1–7 were established by extensive spectroscopic data analyses, X-ray diffraction analysis, and/or quantum chemical calculations. In bioassay, compounds 2, 7, 11 and 12 exhibited considerable anti-inflammatory activity by the inhibition of TNF-α release, with IC50 values of 33.8 μM, 5 μM, 9.9 μM and 8 μM.

The chemical investigation of the South China Sea soft coral

Five novel biscembranoids, ximaolides H–L (1–5), along with four known related compounds (6–9) were isolated from the Hainan soft coral Sarcophyton tortuosum. The structures of the new compounds were determined by extensive spectroscopic analysis, quantum chemical calculations, and/or by comparing their CD spectra with those of the known compounds. Compounds 1 and 2 are the first examples of biscembranoids bearing a 1, 35-bridged lactone moiety, 4 is the first biscembranoid comprising an uncommon oxetane ring, and 5 represents the first 36-peroxyl biscembranoid. Ximaolides I (2), K (4) and F (9) exhibited interesting anti-inflammatory activity by the inhibition of LPS-induced TNF-α protein release in RAW264.7 macrophages., This research work was financially supported by the National Natural Science Foundation of China (NSFC, Nos. 81991521, 8202290170, 42076099), the NSFC/CNRS (Centre national de la recherche scientifique) Joint Project (No. 81811530284), the National Key Research and Development Program of China (No. 2018YFC0310903), and the SKLDR/ SIMM Project (No. SIMM1903ZZ-04). X.-W. Li is also thankful for the Shanghai Rising-Star Program (No. 20QA1411100) and SA-SIBS Scholarship Program. We thank Prof. X.-B. Li from Hainan University for the taxonomic identification of the soft coral material.

Litosetoenins A–E (1–5), five new ring-rearranged serrulatane-type diterpenoids with a common tricyclo[3.0.4]decane core, along with a known diterpenoid glycoside (6), a related known diterpenoid (7), and four known sesquiterpenoids (8–11), were isolated from a Balinese soft coral Litophyton setoensis. Spirolitosetoenin A (5a) and isospirolitosetoenin A (5b), featuring an unprecedented spiro[4,5]decane core, were obtained after treatment of compound 5 with HCl in methanol. The structures of new compounds were elucidated by extensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance approach, and chemical methods. A plausible biosynthetic pathway involving an unusual divergent biogenesis was proposed., This work was financially supported by the National Key Research and Development Program of China (no. 2018YFC0310903), the Natural Science Foundation of China (no. 81991521), the SKLDR/SIMM Project (no. SIMM2103ZZ-06), the Indonesian Ministry of Research and Technology/National Agency for Research and Innovation (WCR grant no. 91/UN48.16/LT/2020), and the Ministerio de Ciencia e Innovación (MICIN PID2019-109476RB-C21). The manuscript was proof-edited by Guido Jones, funded by Cabildo de Tenerife under the TFinnova Programme, supported by MEDI and FDCAN. We thank Prof. X.-B. Li from Hainan University for the identification of the soft coral material. SGAI-CSIC and CESGA (Spain) provided access to supercomputing facilities.

A new diterpenoid with an unusual capnosane skeleton, sinuhumilol A (

A novel diterpenoid, sinueretone A (

Two new C29 steroids, xidaosterols A (

A detailed chemical research of the soft coral Sinularia crassa collected from the South China Sea yielded a series of cembrane-type diterpenoids, including four new cembranoids, namely sinulacrassins A − C (1, (+)-2, (+)-4) and ent-xishaflavalin G ((+)-3), along with five known analogs ((-)-3, 5–8). Their structures were elucidated by detailed spectroscopic analysis, chemical methods, and the comparison with those literature data. The absolute configuration of 1 was established by time-dependent density functional theory electronic circular dichroism (TDDFT/ECD) calculation, and the absolute configuration of (+)-2 was determined using the modified Mosher's method. The bioassay results revealed that (+)-2 and 5 were novel α-glucosidase inhibitors with IC50 values of 10.65 ± 0.16 and 30.31 ± 1.22 μM, respectively. In addition, (+)-2 and 5 were nontoxic towards human normal hepatocyte (LO2) cells at 100 μM. The present results highlighted the unusual coexistence of α and β configurations of C-1 in cembranoids from soft coral in the Order Alcyonacea, and provided new chemotype for the development of α-glucosidase inhibitors used in anti-diabetes treatment.

An unprecedented organocatalytic enantioselective [4 + 2] cycloaddition reaction of vinyl quinolines with dienals is achieved with the synergistic activation of CH3SO3H and a chiral aminocatalyst. The power of the process is demonstrated by its high efficiency of the production of new synthetically and biologically valued chiral quinoline architectures in high yields and with excellent enantioselectivities.

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.

A phytochemical investigation on the MeOH extract of the red alga Laurencia composita Yamada led to the discovery of six new highly halogenated sesquiterpenoids, including two bisabolane-type sesquiterpenoids (1 and 2), one nerolidol derivative (7), and three chamigrane-type sesquiterpenoids (9, 10, and 18), together with 13 known sesquiterpenoids. Their structures, including relative configuration, were elucidated by extensive spectroscopic analysis, and by comparison with data for related known compounds. The absolute configuration at C-10 of laurecomposin A (1) was determined by the modified Mosher's method. Halonerolidol (7) is the first naturally occurring halogenated nerolidol derivative, while compositacin L (9) represents the third example of chamigranes having a C-10 carbonyl group. Antifungal, antibacterial, and receptor tyrosine kinase inhibitory activities of these isolates were evaluated. The results showed that compounds 1–3 and 5 exhibited significant antifungal activity against Microsporum gypseum (Cmccfmza) with MIC values of 4, 8, 8, and 4 μg/mL, respectively. Additionally, compounds 1–3 and 5 also displayed promising antibacterial activity against Gram-positive bacteria Staphylococcus aureus Newman strain with MIC values ranging from 10.9 to 26.8 μg/mL.

A systematically chemical investigation of Citrus changshan-huyou Y.B. Chang resulted in the isolation and structure determination of twelve known natural products, including limonoid ( 1 ), nootkatone ( 2 ), scoparone ( 3 ), β-sitosterol ( 4 ), 3,5,6,7,8,3',4'-heptamethoxyflavone ( 5 ), nobiletin ( 6 ), tangeretin ( 7 ), naringin ( 8 ), hesperidin ( 9 ), neohesperidin ( 10 ), 3,5-dihydroxyphenyl β-D-glucoside ( 11 ), β-sitosterol-D-glucoside ( 12 ). The structure modification of the most abundant compound limonin ( 1 ) further led to eight limonoid derivatives, including epi -limonol ( 1a ), epi -limonyl acetate ( 1b ), and six new compounds epi -limonol A ( 1c ), limonol A ( 1d ), limonol B ( 1e ), epi -limonol B ( 1f ), epi -limonol C ( 1g ), epi -limonol D ( 1h ), which enlarged the chemical diversity of limonin related limonoids. The structures of the new limonoid derivatives were identified by extensive spectroscopic analysis. In bioassay, all the isolates, the semi-synthetic derivatives and the previously isolated limonoids ( 13 - 20 ) in our natural product library were subjected for anti-inflammatory activities evaluation, and several limonoids exhibited the inhibition of TNF-α release.

Covering: 2010 to 2020The class of 2,11-cyclized cembranoids is particularly widespread in marine Octocorallia, especially Alcyonacea and Gorgonacea, and has been extensively studied. Following a previous review published in 2010, the accumulated knowledge from the past decade will be presented here. All 2,11-cyclized cembranoids share a bicyclo[8.4.0]tetradecane core that is in most of the known compounds oxidatively modified to result in the 15-oxatricyclo[6.6.1.02,7]pentadecane system. Multiple further oxidation and acylation patterns can be observed, while halogenated compounds are surprisingly rare. One new sulfur-containing and a few seco-compounds have also been reported. The biosynthetic pathways to this fascinating class of natural products have not been studied to date, but a plausible biosynthetic hypothesis is presented that allows for a structured discussion of the compounds according to their carbon skeletons and oxidation patterns. Biological activities towards 2,11-cyclized diterpenes are also included.

Two new steroids, (22R,23S)-3β-hydroxy-23-methyl-17,20-epoxyergost-5-en-22-yl acetate and (22R,23S)-5-hydroperoxy-23-methyl-5α-17,20-epoxyergost-6-ene-3β,22-diol, were isolated from the South China Sea soft coral Lobophytum sp., together with two related known ones. The structures of all compounds were elucidated by extensive spectroscopic analysis and by comparing their spectral data with those previously reported. The structure of (22R,23S)-3β-hydroxy-23-methyl-17,20-epoxyergost-5-en-22-yl acetate was further confirmed through chemical correlation. All the isolates were evaluated for the in vitro inhibitory activity against NF-κB, a potential target for the treatment of cancer, and (22R,23S)-5-hydroperoxy-23-methyl-5α-17,20-epoxyergost-6-ene-3β,22-diol exhibited moderate inhibition activity with IC50 value of 8.96 μg/mL.

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.

A series of novel marine phidianidine derivatives were designed, synthesized, and evaluated for their immunosuppressive activities during our search of potential immunosuppressive agents with high efficacy and low toxicity from marine sources. These compounds were tested for their inhibitory activity on Con A-induced T cell and lipopolysaccharide-induced B cell proliferation. Compounds 14a and 18c, displaying the most promising inhibitory effects and low toxicities, were further found to possess immune-regulatory activities upon cross-linking of T cell receptor (TCR) and B cell receptor (BCR) on purified T and B cells, respectively.

Three new polyoxygenated diterpenes (1, 3 and 4) of eunicellin-type, namely, 8-n-butyryl-litophynol A, 6-keto-litophynol B and 6-epi-litophynol B, respectively, together with two related known ones (2 and 5), were isolated from the soft coral Cladiella krempfi collected off the Weizhou island, Guangxi Zhuang Autonomous Region, China. The structures of the new compounds were elucidated by extensive spectroscopic analysis and chemical correlation. In bioassay, all the new compounds displayed moderate anti-inflammatory effects.

Eight cembrane-type diterpenoids, namely, (+)-(6R)-6-hydroxyisosarcophytoxide (1), (+)-(6R)-6-acetoxyisosarcophytoxide (2), (+)-17-hydroxyisosarcophytoxide (3), sarcomililatins A–D (4–7), and sarcomililatol (8), were isolated from the soft coral Sarcophyton mililatensis collected from Weizhou Island, Guangxi Autonomous Region, together with 2 known related analogues, (+)-isosarcophytoxide (9) and (+)-isosarcophine (10). 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 1 was established by the modified Mosher׳s method, while the absolute configurations of compounds 4 and 5 were assigned by electronic circular dichroism (ECD) spectroscopy and that of compound 8 was established by time-dependent density functional theory electronic circular dichroism (TD-DFT ECD) calculation. In in vitro bioassays, compound 9 displayed significant cytotoxicity against the human cancer cell lines human promyelocytic leukemia cells (HL-60) and human lung adenocarcinoma cells (A-549) with IC50 values of 0.78±0.21 and 1.26±0.80 μmol/L, respectively. Compounds 4 and 9 also showed moderate inhibitory effects on the TNFα-induced Nuclear factor kappa B (NF-κB, a therapeutical target in cancer) activation, showing IC50 values of 35.23±12.42 and 22.52±4.44 μmol/L, respectively., Graphical abstract Eight new cembrane-type diterpenoids (1–8) were isolated from the soft coral Sarcophyton mililatensis. Compound 9 displayed significant cytotoxicity, and compounds 4 and 9 showed inhibitory effects on the TNFα-induced NF-κB.fx1

Three new cholestane-type sterols bearing an unusual ∆22–24-oxo side chain, namely, dictyoptesterols A–C (1–3), were isolated from the brown alga Dictyopteris undulata Holmes, together with five known strutural analogues (4–8). Their structures were elucidated on the basis of by extensive spectroscopic analysis. The absolute configurations of the steroidal nuclei of the new compounds were proposed by a comparison of NMR data with those of related known compounds as well as biogenetic considerations. All of the isolates were evaluated in vitro for their potential to inhibit protein tyrosine phosphatase-1B (PTP1B) activity. The results showed that compounds 1–5 exhibited different levels of PTP1B inhibitory activities with IC50 values ranging from 3.03 ± 0.76 to 15.01 ± 2.88 μM. In particular, compounds 3 and 4 showed promising inhibitory effects towards PTP1B with IC50 values of 3.03 ± 0.76 and 3.72 ± 0.40 μM, respectively, when compared to the positive control oleanolic acid (IC50, 2.83 ± 0.39 μM). The chemotaxonomic significance of these isolated ∆22–24-oxo cholestanes has also been discussed.

Sarcophytonolides are cembranolide diterpenes isolated from the soft corals of genus Sarcophyton. Unified total synthesis of sarcophytonolides C, E, F, G, H, and J and isosarcophytonolide D was achieved. The synthetic routes feature NaHMDS- or SmI2-mediated fragment coupling, alkoxycarbonylallylation, macrolactonization, and transannular ring-closing metathesis. These total syntheses led to the absolute configurational confirmation of sarcophytonolide H, elucidation of sarcophytonolides C, E, F, and G, and revision of sarcophytonolide J and isosarcophytonolide D. We also evaluated the antifouling activity and toxicity of the synthetic sarcophytonolides H and J and their analogues as well as the cytotoxicity of the synthetic sarcophytonolides and the key synthetic intermediates.

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 novel tetrandrine (Tet) derivatives were synthesized through Suzuki -Miyaura reaction and evaluated for their cytotoxicity against human non-small cell lung carcinoma (NSCLC) A549 cells. Interestingly, most of derivatives showed similar cytotoxicity to Tet against NSCLC A549 cells, and particularly, compounds Y5, Y6, Y9 and Y11 showed the most significant cytotoxic effects with IC50 values ranging from 3.87 to 4.66 mM. The present study is expected to contribute to the future design of more effective anticancer agents in lung cancer chemotherapy.

One new sorbicillin derivative, 2-deoxy-sohirnone C (1), one new diketopiperazine alkaloid, 5S-hydroxynorvaline-S-Ile (2), and two naturally occurring diketopiperazines, 3S-hydroxylcyclo(S-Pro-S-Phe) (3) and cyclo(S-Phe-S-Gln) (4), together with three known compounds were isolated from the Chinese mangrove endophytic fungus Penicillium sp. GD6. Their structures were determined on the basis of extensive spectroscopic analyses and by comparison with literature data. The absolute configuration of 3-hydroxyl moiety in 3 was determined by Mosher's method, while the absolute stereochemistry of 2 and 4 was established by comparison with the CD spectra of natural and synthesized diketopiperazines. Compound 1 showed moderate antibacterial activity against Methicillin-resistant Staphylococcus aureus with a MIC value of 80 μg·mL-1.

Two novel nitrogenous diterpenoids, sarinfacetamides A (1) and B (2), featuring an uncommon tricydo[6.3.1.0(1,5)]dodecane scaffold, and a known related diterpene (3) were isolated from the South China Sea soft coral Sarcophyton infundibuliforme. Their structures, including the absolute configuration of 1, were established, by extensive spectroscopic analysis and TDDFT-ECD calculation. Compounds 1 and 3 exhibited interesting promotion effects on the ConA-induced T lymphocyte proliferation. A plausible biosynthetic pathway for 1 and 2 was also proposed.

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).

Two rare new furan butanolides, namely sponalisolides A (1) and B (2), characterized by an unprecedented furan-bearing trinorsesquiterpene alkyl chain connecting either a butanolide (1) or an N-acyl homoserine lactone moiety (2), were isolated in racemic forms from the Beihai sponge Spongia officinalis, and were further separated, by chiral-phase HPLC, to their corresponding enantiomers 1a/1b and 2a/2b, respectively. The structures, including the absolute stereochemistry, of the two pairs of enantiomeric compounds, were unambiguously established by extensive spectroscopic analysis and biomimetic total synthesis, involving a key Johnson-Claisen rearrangement and a lactone cyclization after epoxidation or dihydroxylation. All the new compounds exhibited the Pseudomonas aeruginosa quorum sensing inhibitory activity.

Chemical study of a Hainan sponge Halichondria sp. resulted in the isolation of eight new formamidobisabolene-based sesquiterpenes halichines A–E (1–3, 7, 8), ent-axinyssine G [(−)-4], ent-axinyssine J [(−)-5], and ent-axinyssine K [(−)-6], along with five related known ones [(+)-4, (+)-5, (+)-6, 10, 11]. Their structures were determined on the basis of extensive spectroscopic analyses, and the absolute configuration of halichine A (1) was determined by Snatzke's method. In bioassay, compounds 3 and 7 displayed considerable anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells.

A detailed chemical investigation of two specimen of South China Sea sponges Halichondria sp. (No. 19-XD-47 and No. 17-XD-87) have resulted in the isolation of three new sterols, namely, halichsterols A (1), B (2) and C (3), together with seven related known ones (4–10). Their structures were determined by extensive spectroscopic analysis and by comparison with the spectral data reported in the literature. In bioassay, compound 2 displayed significantly anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells.

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.

Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was confirmed by Western blotting. Among them, compound 30 showed potent NF-κB inhibitory activity (IC50=2.5μM) and anti-proliferative against MCF-7, A549, H157, and HL-60 cell lines (IC50=6.5-36.2μM). The present study indicated that pregnenolone/2-cyanoacryloyl conjugate I can server asa novel scaffold for developing NF-κB inhibitors and anti-proliferative agents in cancer chemotherapy.

A series of new benzothiazol-based 1,3,4-oxadiazole derivatives were synthesized and evaluated for their neuroprotective effects against Aβ25–35-induced toxicity in SH-SY5Y cells. The bioassay results indicated that most of the tested compounds exhibited promising neuroprotective activity. In particular, compound 2-[[[5-[(4-bromophenylmethyl)thio]-1,3,4-oxadiazol-2-yl]methyl]thio]benzothiazole showed the most potent activity (95.7% of cell viability at 10 μM), better than the positive control EGCG (90.7% of cell viability at 10 μM). Furthermore, compounds 2-[[[5-[(2-bromophenylmethyl)thio]-1,3,4-oxadiazol-2-yl]methyl]thio]benzothiazole, 2-[[[5-[(4-bromo-2-fluorophenylmethylyl)thio]-1,3,4-oxadiazol-2-yl]methyl]thio]benzothiazole, and 2-[[[5-[(4-methoxyphenylmethyl)thio]-1,3,4-oxadiazol-2-yl]methyl]thio]benzothiazole displayed neuroprotective activity similar to EGCG (87.7, 89.1, and 87.7% of cell viability, respectively, at 10 μM). The preliminary SARs analysis indicated that benzene ring is the key factor for the neuroprotective activity and the bromo atom substituted at 4-position of the benzene ring favors the neuroprotective activity. In addition, the fluoro group in the benzene ring appears not beneficial for the neuroprotective activity.

A novel sarsolenane diterpene, named secodihydrosarsolenone (1), as a minor component was obtained from the South China Sea soft coral Sarcophyton trocheliophorum Marenzeller. Its structure was elucidated by detailed spectroscopic analysis. Compound 1 exhibited moderate inhibitory activity (IC50=13.7 µmol•L−1) against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment of type 2 diabetes, representing the first report of PTP1B inhibitory activity for sarsolenane diterpenes. This discovery promotes computational prediction of binding mode between the enzyme and the metabolite, suggesting a crucial role of the residues Tyr46, Ser216 and Arg221 in the binding action.