Ximaoornatins A–C,Polyoxygenated Diterpenoids from the Hainan Soft Coral Sinularia ornata

Three complex polyoxygenated diterpenoids possessing uncommon tetradecahydro-2,13:6,9-diepoxybenzo[10]annulene scaffold, namely ximaoornatins A–C (1–3), one new eunicellin-type diterpene, litophynin K (4), and a related known compound, litophynol B (5) were isolated from the South China Sea soft coral Sinularia ornata. The structures and absolute configurations of 1–4 were established by extensive spectroscopic analysis, X-ray diffraction analysis, and/or modified Mosher’s method. A plausible biosynthetic relationship of 1 and its potential precursor 4 was proposed. In a bioassay, none of the isolated compounds showed obvious anti-inflammatory activity on LPS-induced TNF-α release in RAW264.7 macrophages and PTP1B inhibitory effects.     

A New Spatane Diterpenoid from the Cultured Soft Coral Sinularia leptoclados

A new spatane diterpenoid, leptoclalin A (1), along with two previously reported known norcembranoid diterpenes (2 and 3), were isolated from a cultured soft coral Sinularia leptoclados. The structures were determined by extensive spectroscopic analyses and by comparison with the spectral data of related known compounds. Metabolite 1 is rarely found in spatane skeletons reported from soft corals. In addition, compound 1 exhibited weak cytotoxicity towards human tumor cell lines T-47 D and K-562.     

Lochmolins A-G, New Sesquiterpenoids from the Soft Coral Sinularia lochmodes

Seven new sesquiterpenoids, lochmolins A-G (1-7), were isolated from a Taiwanese soft coral Sinularia lochmodes. The structures of these metabolites were elucidated by extensive spectroscopic study. Compounds 1-4 were found to inhibit the accumulation of the LPS-induced pro-inflammatory COX-2 protein in RAW264.7 macrophage cells.     

Secosteroids and Norcembranoids from the Soft Coral Sinularia nanolobata

Two new 9,11-secosteroids, 22α-acetoxy-24-methylene-3β,6α,11-trihydroxy-9,11-seco-cholest-7-en-9-one (1) and 11-acetoxy-24-methylene-1β,3β,6α-trihydroxy-9,11-seco-cholest-7-en-9-one (2), as well as two known norcembranoids, 5-epi-sinuleptolide (3) and sinuleptolide (4), were isolated from the soft coral Sinularia nanolobata. The structures of these metabolites were elucidated on the basis of extensive spectroscopic analysis. The anti-HCMV (human cytomegalovirus) activity of 1–4 and its cytotoxicity against selected cell lines were evaluated.     

Chemical Diversity and Biological Activity of Secondary Metabolites from Soft Coral Genus Sinularia since 2013

Sinularia is one of the conspicuous soft coral species widely distributed in the world’s oceans at a depth of about 12 m. Secondary metabolites from the genus Sinularia show great chemical diversity. More than 700 secondary metabolites have been reported to date, including terpenoids, norterpenoids, steroids/steroidal glycosides, and other types. They showed a broad range of potent biological activities. There were detailed reviews on the terpenoids from Sinularia in 2013, and now, it still plays a vital role in the innovation of lead compounds for drug development. The structures, names, and pharmacological activities of compounds isolated from the genus Sinularia from 2013 to March 2021 are summarized in this review.     

New Sinularianin Sesquiterpenes from Soft Coral Sinularia sp.

Four new sesquiterpenes, sinularianins C–F (3–6), together with known sinularianins A (1) and B (2) were identified from a South China Sea soft coral Sinularia sp. Compounds 1–6 were evaluated for inhibition of NF-κB activation using the cell-based HEK293 NF-κB luciferase reporter gene assay. Compounds 1 and 4 were exhibited a potent effect with inhibitory rates of 41.3% and 43.0% at the concentration of 10 µg/mL, respectively.     

Secondary Metabolites from the Soft Coral Sinularia arborea

Two new 13-hydroxycembrane diterpenoids, arbolides A (1) and B (2), along with a known trihydroxysteroid, crassarosterol A (3), were isolated from the soft coral Sinularia arborea. The structures of new cembranes 1 and 2 were elucidated by spectroscopic methods. Steroid 3 was found to exhibit cytotoxicity toward K562 and MOLT-4 leukemia.     

Polyoxygenated Sterols from the South China Sea Soft Coral Sinularia sp

Chemical investigation of the ethanol extract of soft coral Sinularia sp. collected from the South China Sea led to the isolation of three new polyoxygenated sterols, (3S,23R,24S)-ergost-5-ene-3β,23α,25-triol (1), (24S)-ergostane-6-acetate-3β,5α,6β,25-tetraol (2), (24S)-ergostane-6-acetate-3β,6β,12β,25-tetraol (3) together with three known ones (4-6). The structures, including relative configurations of the new compounds (1-3), were elucidated by detailed analysis of spectroscopic data (IR, UV, NMR, MS) and by comparison with related reported compounds. The absolute configuration of 1 was further determined by modified Mosher's method. Compound 5 exhibited moderate cytotoxicity against K562 cell line with an IC(50) value of 3.18 μM, but also displayed strong lethality toward the brine shrimp Artemia salina with a LC(50) value of 0.96 μM.     

New Cembrane Diterpenoids from a Hainan Soft Coral Sinularia sp

Five new cembrane diterpenoids, named sinuflexibilins A–E (1–5), along with nine other known diterpenoids (6–14), have been isolated from the organic extract of a Hainan soft coral Sinularia sp. Their structures were determined on the basis of extensive spectroscopic analyses and by comparison of their spectral data with those of related metabolites. Compound 13, flexibilide, exhibited significant inhibitory activity of NF-κB activation using the cell-based HEK293 NF-κB luciferase reporter gene assay.     

Antimicrobial Terpenoids from South China Sea Soft Coral Lemnalia sp.

Chemical investigation of the South China Sea soft coral Lemnalia sp. afforded 13 structurally diverse terpenoids, including three new neolemnane sesquiterpene lineolemnenes E–G (1–3); a new aristolane-type sesquiterpenoid, 2-acetoxy-aristolane (4); four new decalin-type bicyclic diterpenes, named biofloranates A−D (5−8); a new serrulatane, named euplexaurene D (9); and a new aromadendrane-type diterpenoid cneorubin K (10), together with three known related compounds (11−13). The structures of the new compounds were elucidated by NMR spectroscopy, the Mosher’s method, and ECD analysis. Compounds 1–13 were tested in a wide panel of biological assays. Lineolemnene J (3) showed weak cytotoxicity against the CCRF-CEM cancer cell line. The isolated new diterpenes, except euplexaurene D (9), demonstrated moderate antimicrobial activity against Bacillus subtilis and Staphylococcus aureus with a MIC of 4−64 μg/mL. Compound 2 exhibited a mild inhibitory effect against influenza A H1N1 virus (IC₅₀ = 5.9 µM).     

Cembrane Derivatives from the Soft Corals,Sinularia gaweli and Sinularia flexibilis

A new norcembranoidal diterpene, 1-epi-sinulanorcembranolide A (1), and a new cembranoidal diterpene, flexibilin D (2), were isolated from the soft corals, Sinularia gaweli and Sinularia flexibilis, respectively. The structures of new metabolites 1 and 2 were elucidated by spectroscopic methods, and compound 2 was found to significantly inhibit the accumulation of the pro-inflammatory iNOS and COX-2 proteins of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. In addition, S. flexibilis yielded a known cembrane, 5-dehydrosinulariolide (3); the structure, including its absolute stereochemistry, was further confirmed by single-crystal X-ray diffraction analysis.     

Bioactive cembrane-based diterpenoids from the soft coral Sinularia triangular

Chemical examination of the Taiwanese soft coral Sinularia triangular led to the isolation of five cembrane-based diterpenoids 1-5, including two new metabolites, triangulenes A (1) and B (2). The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis, particularly mass spectroscopy and 2D NMR ((1)H-(1)H COSY, HMQC, HMBC, and NOESY) spectroscopy. Metabolites 3 and 5 exhibited moderate cytotoxicity to human tumor cell lines CCRF-CEM and DLD-1. Furthermore, 3-5 displayed significant in vitro anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein. Metabolites 4 and 5 also effectively reduced the expression of the COX-2 protein in the macrophages.     

Isolation of Sesquiterpenoids and Steroids from the Soft Coral Sinularia brassica and Determination of Their Absolute Configuration

Two undescribed rearranged cadinane-type sesquiterpenoids (1–2), named sinulaketol A-B, together with one new chlorinated steroid (3), one new gorgosterol (4), one known sesquiterpene (5), one known dibromoditerpene (6) and two known polyhydroxylated steroids (7–8) were isolated from the soft coral Sinularia brassica. The structures of these compounds were established by extensive spectroscopic analysis, including HRESIMS, 1D, and 2D NMR spectroscopy. Their absolute configurations were also determined by the ECD calculations and DP4+ probability analysis. Antileishmanial activity of compounds 1–8 was evaluated in vitro against the amastigote forms of Leishmania donovani, in which compounds 3, 6, and 7 inhibited the growth of L. donovani by 58.7, 74.3, 54.7%, respectively, at a concentration of 50 μM. Antimicrobial effect of the isolated compounds were also evaluated against Candida albicans, Staphylococcus aureus, and Escherichia coli. Compound 6, a brominated diterpene, exhibited antimicrobial effect against S. aureus.     

Six New Diterpene Glycosides from the Soft Coral Lemnalia bournei

A chemical study on the extracts of soft coral Lemnalia bournei resulted in the isolation and identification of six new bicyclic diterpene glycosides including three new lemnaboursides E–G (1–3), and three new lemnadiolboursides A–C (4–6), along with three known lemnaboursides (7–9). Their structures were elucidated by detailed spectroscopic analysis, ECD analysis, chemical methods, and comparison with the literature data. Lemnadiolboursides A–C (4–6) contained a lemnal-1(10)-ene-7,12-diol moiety compared with the lemnaboursides. All these compounds were evaluated for antibacterial activity; cell growth inhibition of A549, Hela, HepG2, and CCRF-CEM cancer cell lines; and inhibition of LPS-induced NO production in RAW264.7 macrophages. The results indicated that compounds 1, 2, and 4–6 exhibited antibacterial activity against Staphylococcus aureus and Bacillus subtilis (MIC 4–16 μg/mL); compounds 1–9 displayed low cytotoxicity on the CCRF-CEM cell lines (IC₅₀ 10.44–27.40 µM); and compounds 1, 2, and 5 showed weak inhibition against LPS-induced NO production (IC₅₀ 21.56–28.06 μM).     

New Terpenes from the Egyptian Soft Coral Sarcophyton ehrenbergi

Chemical investigations of the Egyptian soft coral Sarcophyton ehrenbergi have led to the isolation of compounds 1–3 as well as the previously reported marine cembranoid diterpene sarcophine (4). Structures were elucidated by comprehensive NMR and HRMS experimentation. Isolated compounds were in vitro assayed for cytotoxic activity against human hepatocarcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines.     

Capilloquinol: a novel farnesyl quinol from the Dongsha atoll soft coral Sinularia capillosa

Capilloquinol (1), possessing an unprecedented farnesyl quinoid skeleton, was isolated from the Dongsha Atoll soft coral Sinularia capillosa. The structure of capilloquinol was elucidated by extensive analysis of spectroscopic data. The cytotoxicity and antiviral activity against human cytomegalovirus of 1 was evaluated in vitro.     

Cubitanoids and Cembranoids from the Soft Coral Sinularia nanolobata

Two new cubitanoids, nanoculones A and B (1 and 2), and three new cembranoids, nanolobols A–C (3–5), as well as six known compounds, calyculone I (6), sinulariuol A (7), sinulariols C, D, H, and J (8–11), were isolated from the soft coral Sinularia nanolobata, collected off the coast of the eastern region of Taiwan. Their structures were elucidated on the basis of extensive spectroscopic analysis. Cytotoxicity of compounds 1–11 was evaluated. The nitric oxide (NO) inhibitory activity of selected compounds was further measured by assay of lipopolysaccharide (LPS)-stimulated NO production in activated RAW264.7 cells. The results showed that none of 1–11 exhibited cytotoxicity against the tested cancer cell lines, whereas compound 8 was found to significantly reduce NO production.     

Bisdioxycalamenene: A Bis-Sesquiterpene from the Soft Coral Rhytisma fulvum fulvum

A dichloromethane extract of the soft coral Rhytisma fulvum fulvum collected in Madagascar afforded a novel compound possessing an unprecedented pentacyclic skeleton, bisdioxycalamenene (1), as well as seven known sesquiterpenes. The structures of the compounds were elucidated using 1D and 2D NMR techniques, as well as high-resolution mass spectrometry. The absolute configuration of 1 was determined using X-ray diffraction analysis and anomalous dispersion effects. The structure elucidation and a possible biogenesis of the compound are discussed.