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A novel norditerpenoid, sinusiaetone A (1), featuring an uncommon bicyclo[11.3.0]hexadecane carbon skeleton, and four polyoxygenated cembranoids (2-5) were isolated from the Hainan soft coral Sinularia siaesensis. Their structures were established by spectroscopic analysis, X-ray diffraction, quantum chemical computational approaches, and/or a modified Mosher's method. A plausible biosynthetic pathway of 1 and its biogenetic relationship with 2-5 were proposed. New compounds 1-3 displayed an interesting inhibitory activity against lipopolysaccharide-induced inflammation in BV-2 microglial cells.

An extract of a Sinularia sp. soft coral showed inhibitory activity against the E3-ubiquitin ligase casitas B-lineage lymphoma proto-oncogene B (Cbl-b). Subsequent bioassay-guided separation of the extract provided a series of terpenoid-derived spermidine and spermine amides that were named sinularamides A–G (1–7). Compounds 1–7 represent new natural products; however, sinularamide A (1) was previously reported as a synthetic end product. The structures of sinularamides A–G (1–7) were elucidated by analysis of spectroscopic and spectrometric data from NMR, IR, and HRESIMS experiments and by comparison with literature data. All of the isolated compounds showed Cbl-b inhibitory activities with IC(50) values that ranged from approximately 6.5 to 33 μM.

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.

Five new tyrosine derivatives (1-5), one new phenylacetic acid derivative (6), two new quinazolinone analogues (7 and 8), one new naphthalenedicarboxylic acid (9), and one new 3,4-dihydroisocoumarin derivative (10), together with seven known compounds, were isolated from the fungus Xylaria sp. FM1005, which was isolated from Sinularia densa (leather coral) collected in the offshore region of the Big Island, Hawaii. The structures of compounds 1-10 were elucidated by extensive analysis of NMR spectroscopy, HRESIMS, and ECD data. Due to their structure similarity to the antiplatelet drug tirofiban, compounds 1-5 together with 6 were investigated for their antithrombotic activities. Compounds 1 and 2 strongly inhibited the binding of fibrinogen to purified integrin IIIb/IIa in a dose-dependent manner with the IC50 values of 0.89 and 0.61 μM, respectively, and compounds 1 and 2 did not show any cytotoxicity against A2780 and HEK 293 at 40 μM.

A pharmacophore-directed retrosynthesis strategy applied to rameswaralide provided simplified precursors bearing the common 5,5,6 (red) and 5,5,7 (blue) skeleton present in several cembranoid and n...

Chemical examination of the soft coral Sinularia capillosa collected from the South China Sea resulted in the isolation of 14 new asteriscane-type sesquiterpenoids, namely, capillosananes A-N (1-14), four new seco-asteriscanes, capillosananes O-R (15-18), and (-)-sinularone A and sinularone A. Their structures were determined on the basis of extensive spectroscopic analyses, while the absolute configurations were determined by CD and ECD calculation, Mosher's method, and chemical conversion. This is the first report of asteriscane-type sesquiterpenoids from soft corals, and capillosananes Q (17) and R (18) represent new seco-asteriscane skeletons. Capillosanane A exhibited potent antifouling activity against Balanus amphitrite, with an IC₅₀ value of 9.70 μM, while capillosananes B and I and (-)-sinularone A inhibited inflammation-related TNF-α in vitro.

Havellockate (1) was isolated from the soft coral Sinularia granosa located on the Havellock island in the Indian Ocean. This highly compact and polyoxygenated marine diterpene bears a cis-fused hydrindane core that contains eight stereogenic centers as well as a spiro-lactone. To the best of our knowledge, no syntheses of 1 have been reported yet. Herein, we describe the synthesis of the all-carbon framework of havellockate (1) in 18 chemical operations. Our approach highlights the efficiency and utility of the hydroxy-directed Diels-Alder (HDDA) reaction to quickly access the cis-fused hydrindane core and securing the correct stereochemistry at C6 and C7. Moreover, six of the eight stereogenic centers have been installed in the correct stereochemistry.

Two new terpenoids, capillosanol (1) and chabranol (2), possessing unprecedented terpenoid skeletons, were isolated from the soft corals Sinularia capillosa and Nephthea chabroli, respectively. The structures of 1 and 2 were elucidated through extensive spectroscopic analyses. The cytotoxicities of these compounds were tested in vitro.

The effects of natural hybridization on secondary metabolite production and diversification have only recently been studied in plants and have essentially been overlooked in marine organisms. Chemical investigation of the hybrid soft coral Sinularia maxima x S. polydactyla resulted in the isolation of five new terpenoids, 7E-polymaxenolide (1), 7E-5-epipolymaxenolide (2), and polymaxenolides A-C (3-5), possessing a cembrane-africanane skeleton. Their structures were established by detailed analysis of NMR and MS data. The contentious issue of defining the absolute configuration at the stereogenic centers of the conformationally mobile cembrane macrocyclic ring was addressed by joint application of electronic circular dichroism and X-ray diffraction analyses.

Four new cembranoids, querciformolides A-D (1-4), along with two known cembranoids, 7 and 8, have been isolated from the soft coral Sinularia querciformis. Furthermore, chemical investigation of Sinularia granosa has afforded three new cembranoids, querciformolide B (2) and granosolides A (5) and B (6). The structures of the new metabolites were elucidated on the basis of extensive spectroscopic methods, and that of 2 was further confirmed by X-ray diffraction analysis. The absolute configurations of 1 and 2 were determined by a modified Mosher's method. Among these metabolites, 2-6 are rarely found cembranoids possessing a tetrahydrofuran moiety with a 4,7-ether linkage; in addition, 1 is the first epsilon-lactone cembrane found that possesses a tetrahydropyran moiety with a 4,8-ether linkage. None of these compounds were found to be cytotoxic toward a limited panel of cancer cell lines. However, compounds 3, 7, and 8 significantly inhibited the accumulation of the pro-inflammatory iNOS and COX-2 proteins in LPS-stimulated RAW264.7 macrophage cells.

Two new diterpenes, sinulodurin A (1) and sinulodurin B (2), along with two known sterols, 24 S-methyl cholesterol and 24-methylene cholesterol, were isolated from the Palau soft coral Sinularia dura. The structures of the new metabolites were determined on the basis of spectroscopic methods and by comparison of NMR data with those of related metabolites. Sinulodurin A (1) and sinulodurin B (2) showed antiproliferative activity against highly malignant +SA mammary epithelial cells with an IC 50 range of 20-30 microM. They also displayed anti-invasive activity against human highly metastatic prostate cancer PC-3M-CT+ cells in the spheroid disaggregation assay. Furthermore, the antimicrobial activities of the isolates were tested.

The first total synthesis of (−)-trans-cembranolide (1), isolated from Sinularia mayi Luttschw., is described. The key step in the synthesis is the diastereoselective Rh-mediated cyclization of the enantiomerically pure diazo ester 4 to the tetrahydrofuran 3a.

The soft coral Sinularia microclavata collected from the bay of Sanya, Hainan Island, China, yielded a new diterpenoid, microclavatin (1), and a known cembranolide, capillolide (2). The structure of compound 1 was determined on the basis of spectroscopic methods and X-ray single-crystal diffraction analysis. Microclavatin (1) showed cytotoxic activities against tumor cell lines KB and MCF with IC50 values of 5.0 and 20.0 microg/mL, respectively, and capillolide (2) showed potent cytotoxic activity against tumor cell lines (A-549) with an IC50 value of 0.5 microg/mL.

Four new tetraprenyltoluquinols (2−5) have been isolated from the Indo-Pacific soft corals Sinularia dura and Nephthea sp. Sindurol (2), isolated from the Sinularia, is a 1,3,5-trialkylated 2,8-dioxabicyclo[3.2.1]octane, and nephthoside (4), obtained from the Nephthea, is a new substituted hydroquinone d-arabinose glycoside. Compounds 3 and 5 are closely related to nephthoside (4). The structure determination of all new compounds was based mainly on 1D- and 2D-NMR spectroscopy and mass spectrometry, as well as some chemical transformations.

A novel norditerpenoid, horiolide (1), has been isolated from an Indian Ocean soft coral of the genus Sinularia. The structural elucidation was achieved by a study of its spectral characteristics. This compound is structurally characterized by a new carbon skeleton having one six-membered cyclohexane ring bearing an isopropylene moiety, a carbonyl group, and one seven-membered ring attached to a five-membered lactone moiety.

The soft coral Sinularia ovispiculata collected on the coasts of the Andaman and Nicobar Islands of the Indian Ocean yielded two new metabolites, (2E,7E)-4, 11-dihydroxy-1,12-oxidocembra-2,7-diene [4] and (2E,7E) -4, 11-dihydroxy-1,1 2-oxidocembra-2,7,15-triene [7], in addition to three known cembrane diterpenes 1-3, four polyhydroxysterols, (24S)-24-methylcholestane-3β,5α,6β,25-tetraol, (24S)-24-methylcholestane-3β,5α,6β,25-tetraol 25-monoacetate, 24-methylenecholest-5-ene-3β,7β,16β-triol-3-O-α-L-fucopyranoside, and 24-methylenecholestane-1α,3β,5α,6β-tetraol (numersterol A), and pregnenolone. Structural elucidation of all compounds was carried out through spectral analysis and chemical reactions

Two new cembrane-type diterpenoids, 14-0-acetylsarcophytol B and 14-O-acetylsarcophytol J, were isolated from the Okinawan soft cotal Sinularia sp. Structutal assignment was made based on spectroscopic analysis and chemical transformation. The absolute configuration of 14-0-acetylsarcophytol B was confirmed by the modified Mosher method

Bioassay-guided fractionation of an aqueous extract of a Philippine Islands collection of the soft coralLobophytum sp. concentrated its HIV-inhibitory activity into fractions rich in cembranoid diterpenes. Lobohedleolide (1), (7Z)-lobohedleolide (2), and a new compound, 17-dimethylaminolobohedleolide (3), were purified from these fractions by HPLC. The structures of compounds 1-3 were elucidated by spectroscopic analyses and by comparison of their spectral data with previously reported values. The relative stereochemistry of the gamma-lactone ring substituents of 3 was determined by 1D NOESY experiments. While several other cembranoids that contain a dimethylamino functional group have been reported from the soft coral Sinularia sp., compound 3 represents the first cembrane diterpene with this functional group isolated from a Lobophytum species. Diterpenoids 1-3 exhibited moderate HIV-inhibitory activity (EC(50) approximately 3-5 microg/mL) in a cell-based in vitro anti-HIV assay.

A new sterol, (22R,23R,24R)-5α,8α-epidioxy-22,23-methylene-24-methylcholest-6-en-3β-ol (1), as well as two known sterols, numersterol A (2) and pregnenolone (3), have been isolated from a soft coral Sinularia sp. The structure of metabolite 1 was determined by spectral analysis. Cytotoxicity of sterols 1−3 toward various cancer cell lines is also reported.

Three new oxygenated africanenes (1-3) have been isolated from the soft coral Sinularia dissecta and were characterized by spectral and chemical studies.

A new marine norditerpenoid, sinulariadiolide, was isolated from Okinawan soft coral of the genus, Sinularia. Its structure was determined by spectroscopic analysis and chemical reaction. This compound is structurally characterized by a new carbon skeleton and two lactonic moieties, five-membered and nine-membered, the latter being conjugated to a 2-hydroxylated carbon−carbon double bond. A possible biogenesis of sinulariadiolide is briefly discussed.

A novel norditerpenoid, sinuleprolide {(1S,5S,8S,10R,11S)-11 -hydroxy-1-isopropenyl-8-methyl-3,6-dioxo-5,8-epoxycyclotetradec-12-ene-10,12-carbolactone} {1}, was isolated from the Okinawan soft coral Sinularia sp. The structure of 1 was established mainly on the basis of nmr spectroscopic data

A highly oxygenated cembranoid 1 has been isolated as a minor constituent from a soft coral, Sinularia dissecta

1316 cm-'; MS, mle (relative intensity) 217 (M', 4), 175 (13), 174 (loo), 162 (16), 159 (28), 56 (15), 43 (36). Anal. Calcd for Cl3HI5NO2: C, 71.86; H, 6.86; N, 6.45. Found: C, 72.10; H, 6.98; N, 6.49. The ketone 32 was reduced in a similar way as that of 7a to give 33 (85%). 6,7-Dihydro-5hydroxy1,6,6-trimethyl-3,4-benzazepin-2(5H)-one (33): mp 188-189 "C (from ethanol); 'H NMR (CDC13) b 1.14 (s,3 H, MeCMe), 2.10 (s,3 H, MeCMe), 2.62 and 2.90 (ABq, J = 14 Hz, 2 H,NCH,),3.08 (9, 3 H,NMe),3.57 (8, 1 H,HCOH), 4.20 (s, 1 H, OH), 7.2-7.8 (m, 4 H, Ar H); IR (KBr) 3305 (OH), 1625 (amide), 1595, 1428, 1256, 1058 cm-l; MS, mle relative intensity) 219 (M', 100), 190 (61), 161 (56), 44 (100). Anal. Calcd for C13H1,N02: C, 71.20; H, 7.82; N, 6.39. Found C, 71.20; H

The steroid glycoside 1 has been isolated from the Sri Lankan soft coral Sinularia crispa. The structure has been determined by spectroscopic (1H and 13C nmr) techniques. Glycoside 1 showed spermatostatic activity on rat cauda epididymal spermatozoa.