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Chemical investigation of the soft coral Cespitularia sp. led to the discovery of twelve new verticillane-type diterpenes and norditerpenes: cespitulins H–O (1–8), one cyclic diterpenoidal amide cespitulactam L (9), norditerpenes cespitulin P (10), cespitulins Q and R (11 and 12), four new sesquiterpenes: cespilins A–C (13–15) and cespitulolide (16), along with twelve known metabolites. The structures of these metabolites were established by extensive spectroscopic analyses, including 2D NMR experiments. Anti-inflammatory effects of the isolated compounds were studied by evaluating the suppression of pro-inflammatory protein tumor necrosis factor-α (TNF-α) and nitric oxide (NO) overproduction, and the inhibition of the gene expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide-induced dendritic cells. A number of these metabolites were found to exhibit promising anti-inflammatory activities.

In the present study, a new ceramide, namely 2S, 3R-4E, 8E-2-(heptadecanoylamino)-heptadeca-4, 8-diene-1, 3-diol (1), along with four known steroids, including 24-methylcholesta-5, 24(28)-diene-3β-ol (2), 24-methylcholesta-5, 24(28)-diene-3β-acetate (3), 4-methyl-24-methylcholesta-22-ene-3-ol (4), and cholesterol, was isolated and characterized from CH2Cl2/MeOH extract of Cespitularia stolonifera. A new acetate derivative of compound 1, termed 2S, 3R-4E, 8E-2-(heptadecanoylamino)-heptadeca-4, 8-diene-1, 3-diacetate (1a), was also prepared in the present study. All the structures were established on the basis of modern spectroscopic techniques, including FT-IR, 1D, 2D-NMR, HRESI-MS, and GC-MS, in addition of chemical methods. (-)-Alloaromadendren, ledane, (1)-alloaromadendren oxide, isoaromadendrene epoxide and (-)-caryophellen oxide were identified from the n-hexane fraction using GC-MS. The extract and the two ceramides (1) and (1a) exhibited significant cytotoxic activity against lung cancer A549 cells, while the extract and the two steroids (2) and (3) exhibited significant cytotoxic activity against breast cancer MCF-7 cells. The CH2Cl2/MeOH extract exhibited significant antiulcer activity in both ethanol and acetic acid induced ulcer models in rats, as evidenced by histopathological, histochemical, and biochemical examinations.

In our current study, alcyonolide and its congeners isolated from the Okinawan soft coral, Cespitularia sp., have shown an antitumor activity in HCT116 colon cancer cells. This study investigated the biological activities of these compounds (1-12) for the apoptotic activity in the HCT116 cells and the anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. As a result, the apoptotic cells with a nuclear condensation were detected by treatment with these compounds. The apoptotic cells dependent on the caspase 3/7 activation was also induced in the low concentration range of 2.5-10 μM. While a similar concentration of the compounds inhibited the NO production in the LPS-stimulated inflammatory RAW264.7 cells, the pro-inflammatory gene expressions of the iNOS and COX-2 mRNA were also suppressed. The structurally unique alcyonolides (5, 12) having the dual biological activity of apoptotic activity and anti-inflammatory effect could be a potential development as pharmaceutical agents.

An Okinawan soft coral Cespitularia sp. has proven to be a good source of cytotoxic metabolites having a carbon skeleton of the seco-type variety of xenicin. This soft coral yielded alcyonolide, the major constituent, and other related compounds, all of which have proven to be cytotoxic. Reinvestigation of the cytotoxic ethyl acetate extracts of the coral yielded two new alcyonolide congeners, trisnorditerpenoid 1 and diterpenoid 2 , possessing the same carbon skeleton. Their structures were elucidated by a detailed analysis of spectroscopic data (1D, 2D NMR, and MS). Metabolites 1 and 2 showed cytotoxicity against HCT116 cells (IC 50 6.04 and 47.0 μM, respectively) and a dose dependent, anti-inflammatory effect in LPS/IFN-γ-stimulated inflammatory RAW 264.7 macrophage cells.

Four novel diterpenoids, designated cespitulins A–D ( 1 – 4 ) were isolated and characterized from the Taiwanese soft coral Cespitularia taeniata . Their structures were determined by extensive spectroscopic analyses ( 1 H- 1 H COSY, HMQC, HMBC, NOESY). Compounds 1 – 4 possess an unprecedented bond cleavage between C-9 and C-10 with a hemiacetalic lactone ring rather than a verticillane skeleton.

Four new diterpenes, cespihypotins W–Z (1–4), having the verticillane skeleton and characterized by an α,β-unsaturated γ-hydroxycyclopentanone moiety, and a new eudesmanolide-type sesquiterpene, cespilactam A (5), containing an α,β-unsaturated γ-lactam residue, were isolated from the AcOEt-soluble fraction of the Taiwanese soft coral Cespitularia hypotentaculata. The structure and relative configuration of these metabolites was elucidated through extensive interpretation of MS, COSY, HSQC, HMBC, and NOESY experiments and by comparison of their NMR data with those of related compounds.

Chemical investigations of the Formosan soft coral Cespitularia hypotentaculata ROXAS led to the isolation of two new verticillane diterpenoids, cespitularins R and S (1, 2), along with seven known compounds (3-9). The structures of these isolated compounds were elucidated on the basis of extensive spectroscopic analysis and by comparison with those of reported in literature. The anti-inflammatory activity using RAW 264.7 macrophages of compounds 1-9 were evaluated in vitro.

Five new diterpenes, cespihypotins W–Z (1–4, resp.) and cespihypotone (5) have been isolated from the AcOEt-soluble fraction of the Formosan soft coral Cespitularia hypotentaculata. Two of them having the norverticillane skeleton, i.e., 1 and 2, and the other three, 3–5, possessing a verticillane skeleton. The structures were established as (+)-(1βH,7E)-6β,11β-dihydroxynorverticilla-4(18),7-diene-10,12-dione (1), (+)-(1βH,7E)-6β-acetoxy-11β-hydroxynorverticilla-4(18),7-diene-10,12-dione (2), (−)-(1βH,7E)-6β-acetoxyverticilla-4(18),7,11-triene-10,12-γ-lactone (3), (+)-(1βH,7E)-6β-acetoxy-10-hydroxyverticilla-4(18),7,11-triene-10,12-γ-lactone (4), and (+)-(1βH,3Z)-10β-hydroxy-6-oxoverticilla-3,11-diene-10,12-γ-lactone (5), respectively, on the basis of 1D- and 2D-NMR spectroscopic analyses.

Chemical investigation of the soft coral Cespitularia hypotentaculata resulted in the isolation of six new diterpenes, cespihypotins Q-V. The new metabolites comprised five verticillane-type diterpenes and one nor-verticillane derivative. Their structures were determined through detailed spectroscopic analyses, especially HRESIMS and 2D NMR techniques. The relative configuration was deduced by interpretation of NOESY spectra. Cespihypotin T exhibited significant cytotoxic activity against human Daoy and WiDr tumor cell lines.

Investigation of the MeOH/CH2Cl2 extract of the soft coral Cespitularia hypotentaculata collected in Taiwan has resulted in the isolation of four new verticillane-type diterpenoids, cespihypotins M–P (1–4). Compounds 2 and 3 are C(20)-epimers. Compound 4 with a CO group at C(10) and a methoxycarbonyl group at C(12) may be an important precursor of cespitularins and cespihypotins. The structures of these compounds were determined on the basis of spectroscopic analyses.

Chemical investigation of the soft coral Cespitularia hypotentaculata resulted in the isolation of eight new diterpenes, cespihypotins E–L ( 1 – 8 ). The new metabolites comprise of six verticillene-type diterpenes, one cespitularane derivative, and one derivative with 14-membered lactone ring. The structures were determined through detailed spectroscopic analyses, especially high resolution ESIMS and 2D NMR techniques. The relative stereochemistry was deduced from NOESY spectrum and application of Mosher's ester technique. Immunomodulatory and antiviral activities of 1 – 8 were tested and evaluated. The biogenetic pathways for 1 – 8 were also proposed.

Two new nitrogen-containing verticillene diterpenoids, cespilamides A and B (1 and 2), three new nitrogen-containing sesquiterpenoids, cespilamides C–E (3–5), and five new norverticillene and verticillene diterpenoids, cespitaenins A–E (6–10), were isolated from the Taiwanese soft coral Cespitularia taeniata. Compound 1 possesses an unusual oxazo ring system at C-10 while compound 2 displays an unprecedented C–C bond cleavage between C-10 and C-11 with an N-ethylphenyl group at C-10. Biogenetic pathways of 1 and 2 are proposed. The absolute configuration of 1 was confirmed by Mosher’s method and molecular mechanics calculations (MM2). The cytotoxicities of compounds 1–10 were evaluated against a small panel of human cancer cell lines.

Four new norditerpenoids, designated as cespihypotins A ( 1 ), B ( 2 ), C ( 3 ) and D ( 4 ), were isolated from Cespitularia hypotentaculata Roxas (Xeniidae) that was collected in Taiwan. Compounds 1 and 2 are unprecedented structures having 13- and 14-membered lactone ring, respectively. Their structures were elucidated on the basis of extensive spectroscopic analysis. A plausible biogenetic pathway for compounds 1 – 4 was also proposed.

Four new cytotoxic diterpenes, cespitularins A-D (1-4), having the verticillane skeleton, a new cytotoxic norditerpene, cesputularin E (5), that possesses a novel norverticillane skeleton, and three new diterpenes, cespitularins F-H (6-8), possessing a novel carbon skeleton named cespitularane, were isolated from the methylene chloride solubles of the Formosan soft coral Cespitularia hypotentaculata. The structures of cespitularins A-H (1-8) were elucidated by 1D and 2D NMR spectral analysis, and their cytotoxicity against selected cancer cells was measured in vitro.

Five new diterpenoids 1–5 were isolated from an Okinawan soft coral, Cespitularia sp., together with the known diterpenoid, alcyonolide (6). New diterpenoid structures were elucidated by spectroscopic methods and by comparison of their NMR data with those of related compounds. Alcyonolide (6) was cytotoxic against HCT 116 cells (IC50 5.85 μM), while these new diterpenoids 1–5 were much less active (IC50 28.2–91.4 μM).

Extensive column chromatography of the ethanolic extract of the soft coral Cespitularia taeniata collected in Taiwan has resulted in the isolation of eight new nitrogen-containing verticillene diterpenes, designated cespitulactams D-K ( 1- 8), together with three known diterpenes, cespitulactams A ( 9) and B ( 10) and cespitularin F. In addition, one new derivative, 6- O-acetylcespitulactam F ( 11), was prepared from compound 3. The structures of these compounds were elucidated on the basis of spectroscopic analyses, especially HRMS and 2D NMR experiments. The cytotoxicity against human oral epidermoid carcinoma (KB) and murine L1210 leukemia cell lines and antimicrobial activities of 1- 8 and 11 were tested and evaluated. A biogenetic pathway for these novel diterpene alkaloids was also proposed.

Four new cespitularane diterpenes, cesputularins I-L (1-4), two new norverticillane norditerpenes, cespitularins M and N (5 and 6), two new verticillane diterpenes, cespitularins O and P (7 and 8), a new norditerpene, cespitularin Q (9) (having a novel carbon skeleton), a new xenicane diterpene, cespitolide (10), and two new secosteroids, 3beta,11-dihydroxy-5beta,6beta-epoxy-9,11-secocholestan-9-one (11) and 3beta,11-dihydroxy-5beta,6beta-epoxy-9,11-secogorgostan-9-one (12), were isolated from the methylene chloride solubles of the Formosan soft coral Cespitularia hypotentaculata Roxas. The structures were elucidated by extensive spectroscopic analysis, and their cytotoxicity against selected cancer cells was measured in vitro.

Three new nitrogen-containing diterpenoids, designated cespitulactams A (1), B (2), and C (3), were isolated from Cespitularia taeniata May. Compounds 1–3 are novel structures having a phenylethyl amino side at C-10 and with an amide function at C-20. Their structures were determined on the basis of extensive spectroscopic analysis and chemical correlation. The cytotoxicity of 1 and its monoacetate (6) were also evaluated against human cancer cell lines.

Two new diterpenoids, designated cespitulactones A (1) and B (2), were isolated from a sample of the soft coral Cespitularia taeniata collected in Taiwan. Compound 1 possesses a novel structure with a bond cleavage between C-10 and C-11, and having a 14-membered lactone ring junction between C-10 and C-12. Their structures were elucidated on the basis of extensive spectroscopic analysis and chemical derivatization. The isolated compounds were also evaluated for cytotoxicity toward human cancer cell lines.

From a sample of the soft coral Cespitularia sp., a new caryophyllene-basedcaryophyllene-based direrpene 1 was isolated and charactetized. This is the first report of this structural class in animals of the genus Cespitularia

In order to demonstrate the power utility of the interactive computer program CONGEN, 5 an example describing its use in the identification of the tricyclic sesquiterpene alcohol, [+]-palustrol, in extracts of a marine Xeniid ( Cespitularia sp., aff subviridis ) is provided. The rotation of [+]-palustrol further supports the remarkable antipodal relationiship between sesquiterpenes from marine Coelenterates and their corresponding terrestrial forms. 6