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Eight new meroditerpenoid-related metabolites, including one naphthoquinone derivative, chabrolonaphthoquinone B (1), four tetraprenyltoluquinone-related compounds, chabrolobenzoquinones E−H (2−5), and three tetraprenyltoluquinol-related metabolites, chabrolohydroxybenzoquinones E−G (6−8), were isolated from the organic extract of a Taiwanese soft coral Nephthea chabrolii. The structures of 1−8 were elucidated on the basis of extensive spectroscopic analysis and by comparison of the data with those of the related metabolites. Cytotoxic activity of metabolites 1−3 and 5−8 against a limited panel of cancer cell lines is also described.

A series of cardenolides and related compounds have been isolated from the aerial parts and roots of the ornamental milkweed, Asclepias curassavica. Their structures were determined by spectroscopic and chemical methods. Among them, three derivatives of calactinic acid methyl ester (13−15), 19-nor-16α-acetoxy-10β-hydroxyasclepin (16), 20β,21-dihydroxypregna-4,6-dien-3-one (19), and 3,4-seco-urs-20(30)-en-3-oic acid (22) are new compounds. The relative configuration of calactinic acid methyl ester (12) has been confirmed by X-ray diffraction analysis on its derivative 13. Most of the cardenolides obtained showed pronounced cytotoxicity against four cancer cell lines (IC50 0.01 to 2.0 μg/mL).

Two new monotetrahydrofuran Annonaceous acetogenins, montacin (1), and cis-montacin (2), along with four known acetogenins, annonacin, cis-annonacin, annomontacin, and cis-annomontacin, were isolated from the seeds of Annona montana. The structures of the new isolates were elucidated by spectral and chemical methods. The new acetogenins exhibited moderate in vitro cytotoxic activity against the 1A9 human ovarian cancer cell line. Interestingly, when Ca²⁺ was present, compounds 1 and 2 became 3- to 10-fold more active against 1A9 cells and the PTX10 subline.

Twenty-one compounds, including five new agarofuran sesquiterpenes, reissantins A−E (1−5), were isolated from Reissantia buchananii by means of bioassay-directed fractionation and their structures identified from spectral data. Reissantins A−C are the first reported simple agarofuran sesquiterpenes to contain a 5-carboxy-N-methyl-2-pyridone (CNMP) substituent, which has previously been found only in macroring agarofuran pyridine alkaloids. The major terpenoid components, celastrol (6) and its methyl ester derivative, pristimerin (7), were significantly active against nine cancer cell lines, including A549, MCF-7, HCT-8, KB, KB-VIN, U-87-MG, PC-3, 1A9, and PTX10 cell lines, with ED50 values ranging from 0.076 to 0.34 μg/mL.

A new secoiridoid glycoside, hydrachoside A (1), along with 14 known compounds, was isolated from the leaves of Hydrangea chinensis. The absolute stereochemistry of the side chain attached to C-15 on the secoiridoid glycoside hydrangenoside E (2) was determined by NMR spectral analysis. The structures of compounds 1 and 2 were elucidated on the basis of spectral data. The previously reported structure, hydrachine A (3), was revised as its epimer, (−)-neodichroine (4), a new compound.

A new triterpene, laxifolone A (1), four known sesquiterpene alkaloids, ebenifoline E-II (2), carigorinine E (3), euojaponine C (4), and emarginatine E (5), and six triterpenoids, 3-hydroxyolean-12-en-22,29-γ-lactone, 3,11-dioxo-β-amyrene, 3β,22α-dihydroxyolean-12-en-29-oic acid, 28,29-dihydroxyfriedelan-3-one, 29-hydroxy-3-oxo-D:A-friedooleanan-28-oic acid, and putranjivadione, were isolated from the stems and leaves of Euonymus laxiflorus. Structural elucidations of these compounds were established by spectral analysis. Compound 1 displayed significant nitric oxide (NO) inhibitory effect.

Two new styrylpyrones, (6R,7R,8R)-8-methoxygoniodiol (1) and (6R,7R,8R)-8-chlorogoniodiol (2), together with seven known styrylpyrones and eight other known compounds, were isolated from the leaves and/or stems of Goniothalamus amuyon. The structures of 1 and 2 were elucidated by spectral data interpretation, and the absolute stereochemistry of styrylpyrones in the diol and triol series was confirmed by X-ray crystallographic analysis and CD spectral data. Compound 2 demonstrated significant selective cytotoxicity toward the HONE-1 cancer cell line.

Seven new compounds, including three new flavans [tupichinol A−C (1−3)], three new spirostanol sapogenins [tupichigenin D−F (4−6)], and one new pregnane genin [tupipregnenolone (7)], together with 18 known compounds, were isolated from the underground parts of Tupistra chinensis. The structures of the new compounds were elucidated by spectroscopic analysis and chemical evidence. The structures and relative stereochemistry of 1 and 9 were further confirmed by single-crystal X-ray crystallographic analysis. Compounds Δ²⁵⁽²⁷⁾-pentrogenin, 10, and ranmogenin A showed 100%, 96%, and 80% inhibition, respectively, against human gastric tumor (NUGC) cells at a concentration of 50 μM. Δ²⁵⁽²⁷⁾-pentrogenin showed 100% inhibition against human nasopharyngeal carcinoma (HONE-1) cells at a concentration of 50 μM.

A phytochemical investigation on the stems of Annona squamosa led to the isolation of six new ent-kaurane diterpenoids, annomosin A (16β-hydroxy-19-al-ent-kauran-17-yl 16β-hydro-19-al-ent-kauran-17-oate) (1), annosquamosin C (16α-hydro-17-hydroxy-19-nor-ent-kauran-4α-ol) (2), annosquamosin D (16β-acetoxy-17-hydroxy-19-nor-ent-kauran-4α-ol) (3), annosquamosin E (16β-hydroxy-17-acetoxy-19-nor-ent-kauran-4α-formate) (4), annosquamosin F (16β-hydroxy-17-acetoxy-18-nor-ent-kauran-4β-hydroperoxide) (5), and annosquamosin G (16β,17-dihydroxy-18-nor-ent-kauran-4β-hydroperoxide) (6), along with 14 known ent-kaurane diterpenoids. The structures of 1−6 were elucidated by spectroscopic data interpretation. Compound 1 is the first dimeric ent-kaurane derivative to have been reported from a plant in the family Annonaceae. Certain useful NMR data were generalized to determine the stereochemistry of C-16 among the ent-kaurane diterpenoids investigated. ent-Kaur-16-en-19-oic acid (9) and 16α-hydro-19-al-ent-kauran-17-oic acid (17) showed complete inhibitory effects on rabbit platelet aggregation at 200 μM.

Three new monotetrahydrofuran annonaceous acetogenins, muricin H (1), muricin I (2), and cis-annomontacin (3), along with five known acetogenins, annonacin, annonacinone, annomontacin, murisolin, and xylomaticin, were isolated from the seeds of Annona muricata. Additionally, two new monotetrahydrofuran annonaceous acetogenins, cis-corossolone (4) and annocatalin (5), together with four known ones, annonacin, annonacinone, solamin, and corossolone, were isolated from the leaves of this species. The structures of all new isolates were elucidated and characterized by spectral and chemical methods. These new acetogenins exhibited significant activity in in vitro cytotoxic assays against two human hepatoma cell lines, Hep G2 and 2,2,15. Compound 5 showed a high selectivity toward the Hep 2,2,15 cell line.

Three new eudesmanolide sesquiterpenes, neolitacumone A−C (1−3), and one new benzylisoquinoline alkaloid, neolitacumonine (5), along with 27 known compounds were isolated from the stem bark of Neolitsea acuminatissima. The structures of compounds 1−3 and 5 were established on the basis of spectral and chemical evidence. Compounds 2, 3, and 20 were selectively inhibitory to Hep 2,2,15 cells with IC50 values in the range 0.24−0.04 μg/mL. Compound 20 was marginally cytotoxic to Hep G2 cells.

A novel type of α,β-butenolide alkaloid, uncinine (1), two novel oxoaporphines, artabonatine C (2) and artabonatine D (3), a new oxazoloaporphine, artabonatine E (4), and a new 7,7‘-bisdehydroaporphine, artabonatine F (5), along with 25 known alkaloids, were isolated from Artabotrys uncinatus. The structures of 1−5 were determined using NMR and mass spectral data. Atherospermidine and squamolone exhibited cytotoxicity against hepatocarcinoma cancer cell lines (Hep G2 and 2,2,15), and the activity of some of the alkaloids in an antithrombin assay is also discussed.

Seven new annonaceous acetogenins, muricins A−G (1−7), as well as five known compounds, a mixture of muricatetrocin A (8) and muricatetrocin B (9), longifolicin (10), corossolin (11), and corossolone (12), were isolated from the seeds of Annona muricata. The structures of all isolates were elucidated and characterized by spectral and chemical methods. These acetogenins showed significantly selective in vitro cytotoxicities toward the human hepatoma cell lines Hep G2 and 2,2,15.

A new guaipyridine sesquiterpene alkaloid, cananodine (1), and two new eudesmane sesquiterpenes, cryptomeridiol 11-α-l-rhamnoside (2) and γ-eudesmol 11-α-l-rhamnoside (3), along with γ-eudesmol (4), were isolated from the fruits of Cananga odorata. The structures of compounds 1−3 were established on the basis of NMR and MS methods. In addition, compounds 1−4 and four previously reported alkaloids, cleistopholine (5), N-trans-feruloyltyramine (6), (+)-ushinsunine-β-N-oxide (7), and lyscamine (8), were evaluated for cytotoxicity against two human hepatocarcinoma cell lines.

A new halimane diterpene, 3β,5β,16α-trihydroxyhalima-13(14)-en-15,16-olide (1), and a new oxoprotoberberine alkaloid, (−)-8-oxopolyalthiaine (2), along with 20 known compounds, were isolated from a methanolic extract of Polyalthia longifolia var. pendula. The structures of compounds 1 and 2 were established by spectroscopic analysis. Several of these compounds were evaluated for cytotoxicity toward a small panel of human cell lines.

Investigation of extracts of Fissistigma balansae and Fissistigma oldhamii resulted in the isolation of 11 aristolactams&sbd;stigmalactam (1), piperolactam A (2), piperolactam C (3), aristolactam AII (4), aristolactam AIIIa (5), aristolactam BII (6), aristolactam BIII (7), aristolactam FII (8), goniothalactam (9), enterocarpam I (10), and velutinam (11)&sbd;as well as two dioxoaporphines, noraristolodione (12) and norcepharadione B (13). The new compound 1 was identified by spectral data interpretation. Compounds 1−13 were subjected to antiplatelet aggregation testing.

Three new kaurane diterpenoids, annoglabasin C (16α-acetoxy-ent-kauran-19-oic acid-17-methyl ester) (1), annoglabasin D (16α-acetoxy-ent-kauran-19-al-17-methyl ester) (2), and annoglabasin E (16α-hydro-19-ol-ent-kauran-17-oic acid) (3), and a new norkaurane diterpenoid, annoglabasin F (16α-acetoxy-19-nor-ent-kauran-4α-ol-17-methyl ester) (4), along with 13 known kaurane derivatives were isolated from the stems of Annona glabra. 16α-Methoxy-ent-kauran-19-oic acid (5) and 16α-hydro-ent-kauran-17,19-dimethyl ester (6) were obtained for the first time as natural products. The structures of compounds 1−6 were characterized by spectral analysis.

Four new compounds, a mixture of 20,23-cis-2,4-trans-bullatalicinone (1) and 20,23-cis-2,4-cis-bullatalicinone (2), rollimusin (3), and rolliacocin (4), along with eight known acetogenins, were isolated from an ethyl acetate extract of the unripe fruits of Rollinia mucosa. The structures and stereochemistry of 1−4 were determined on the basis of spectral data and chemical evidence.

The oxidation of zeylanidine (1) afforded two new sesquiterpene dilactones, 4 and 5, besides two known compounds, neoliacine (2) and zeylanidinone (3). The structures of the novel oxidized products were elucidated on the basis of spectroscopic techniques, and the structure of compound 5 was further confirmed by X-ray crystallographic analysis. The mechanism for the oxidation of 1 to 4 and 5 has been postulated.

Bioactivity-directed fractionation led to the isolation of 19 compounds, including three oxoaporphines, oxopurpureine (5), oxonuciferine (6), and oxoglaucine (7); three aporphines, (+)-predicentrine (8), (−)-glaucine (9), and thalbaicalidine (10); one aporphine sensu stricto, N-formyl-purpureine (11); one proaporphine, glaziovine; one phenanthrene, thalicpureine (12); two 6a,7-dehydroaporphines, dehydrolirinidine (13) and 7-hydroxy-dehydroglaucine (14); four flavonoids, quercetin-3-O-rhamnoside, kaempferol-3-O-rhamnoside, isorhamnetin-3-O-rhamnoside, and tanarixetin-3-O-rhamnoside; one purine, adenine; one lactam amide, squamolone; and two steroids, β-sitosterol and β-sitosterol-β-d-glucoside from the MeOH extract of the leaves of Formosan Annona purpurea. Among them, 11−14 were characterized as new compounds and alkaloids, 5−8, 10, and 12−14 exhibited significant antiplatelet aggregation activity.

Using a bioassay-directed fractionation method, three new compounds, including an aporphine alkaloid, cassyformine (4); an oxoaporphine alkaloid, filiformine (8), and a lignan, (+)-diasyringaresinol (10), along with 14 known compounds, were further isolated and characterized from the MeOH extract of the fresh herbs of Cassytha filiformis. Among the isolates of this plant, cathafiline (1), cathaformine (2), actinodaphnine (3), N-methylactinodaphnine (5), predicentrine (6), and ocoteine (7) exhibited significant antiplatelet aggregation activity.

A new hexacyclic triterpenoid, mudanpinoic acid A (1), and a new gallic acid glycoside, mudanoside B (2), along with nine known compounds&sbd;benzoic acid, resacetophenone, paeoniflorigenone, β-sitosterol, betulinic acid, oleanoic acid, quercetin, β-sitosterol-β-d-glucoside, and trans-caffeic acid stearyl ester&sbd;were isolated from the dried root cortex of Paeonia suffruticosa. The structures of the novel compounds were elucidated on the basis of spectral methods, and that of compound 1 was confirmed by X-ray crystallographic analysis.

Members of a series of benzylisoquinoline and phenanthrene alkaloids were tested for their antiplatelet and vasorelaxing actions. Atherosperminine HClO4 (15) and atherosperminium I (16) showed strong inhibition of adenosine 5‘-diphosphate-induced platelet aggregation. dl-N-Methylcoclaurine (1), dl-coclaurine (6), 15, 16, xylopine hydroxylamine (18), and atherosperminine N-oxide (19) showed strong inhibition of arachidonic acid-induced platelet aggregation. Compounds 1, 15, 16, dicentrine methine (17), 18, and 19 showed strong inhibition of collagen-induced platelet aggregation. d-(−)-Magnocurarine I (8), 15, and 16 showed strong inhibition of platelet-activating factor-induced platelet aggregation. Compounds 15, 17, and 19 showed vasorelaxing action in rat thoracic aorta.

A series of N-fatty acyl tryptamines, including a mixture of N-nonadecanoyltryptamine (1), N-behenoyltryptamine (2), N-lignoceroyltryptamine (3), N-cerotoyltryptamine (4), and N-octacosanoyl tryptamine (5), and a mixture of N-tricosanoyl-4,5-dihydroxytryptamine (6), N-lignoceroyl-4,5-dihydroxytryptamine (7), N-pentacosanoyl-4,5-dihydroxytryptamine (8), and N-heptacosanoyl-4,5-dihydroxytryptamine (9), along with two alkaloids, atemoine (10) and cleistopholine, were isolated from the EtOAc extract of seeds of Annona atemoya. The structures of the new compounds, 1 and 5−10, were determined on the basis of spectral evidence.

A novel anti-HIV alkaloid, drymaritin (1), and a new C-glycoside flavonoid, diandraflavone (2), along with eight known compounds, torosaflavone A, isovitexin, spinasterol β-d-glycoside, p-hydroxybenzoic acid, p-hydroxybenzaldehyde, cis-p-coumarate, methyl 5-hydroxy-4-oxopentanoate, and glycerol-α-lignocerate, were isolated from Drymaria diandra. Drymaritin (1) exhibited anti-HIV effects in H9 lymphocytes with an EC50 value of 0.699 μg/mL and a TI of 20.6. Compound 2 showed significantly selective inhibition on superoxide anion generation from human neutrophils stimulated by fMLP/CB with an IC50 value of 10.0 μg/mL.

Rollicosin (1), a new Annonaceous acetogenin, was isolated from the unripe fruits of Rollinia mucosa. Rollicosin (1) is the first compound of this type to contain lactone moieties on both sides of the aliphatic chain and to lack either tetrahydrofuran or tetrahydropyran rings. Its structure was determined on the basis of spectroscopic analyses. This compound may serve as a new prototype molecule to develop Annonaceous acetogenins as potential antitumor agents.

Three new alkaloids, promucosine (1), romucosine F (2), and romucosine G (3), along with 28 known compounds, were isolated from the MeOH extract of stems of Annona purpurea. The structures of 1−3 were determined on the basis of spectral data and chemical evidence.

From the underground parts of Tupistra chinensis, a novel polyhydroxylated spirostanol sapogenin, tupichigenin A [(20S,22R)-spirost-25(27)-ene-1β,2β,3β,5β-tetraol] (1), was isolated and determined structurally on the basis of spectroscopic methods. Also isolated was the known steroidal sapogenin (20S,22R)-spirost-25(27)-ene-1β,2β,3β,4β,5β,7α-hexaol-6-one (2).

Investigation of the ethanolic extract from the twigs of Fissistigma balansae resulted in the isolation of two new p-quinonoid aporphine alkaloids, named fissilandione (1) and norfissilandione (2). The structures of 1 and 2 were elucidated on the basis of spectral data and confirmed by chemical conversions.

Phytochemical analysis of the fruits of Annona glabra yielded two new kaurane diterpenoids, annoglabasin A (methyl-16β-acetoxy-19-al-ent-kauran-17-oate)(1) and annoglabasin B (16α-hydro-19-acetoxy-ent-kauran-17-oic acid)(2), along with 11 known kaurane derivatives (3−13). The structures of the new compounds were established by spectral and chemical evidence. Among these, methyl-16α-hydro-19-al-ent-kauran-17-oate (11) exhibited mild activity against HIV replication in H9 lymphocyte cells, and 16α-17-dihydroxy-ent-kauran-19-oic acid (4) showed significant inhibition of HIV-reverse transcriptase.

Using antiplatelet aggregation as a guide to fractionation, seven aporphines, actinodaphnine (1), N-methylactinodaphnine (2), launobine (3), dicentrine (4), O-methylbulbocapnine (5), hernovine (7), and bulbocapnine (9), and two oxoaporphines, dicentrinone (6) and liriodenine (8), were isolated from the stems of Illigera luzonensis. Among them, compounds 2, 4, 5, 8, and 9 were isolated for the first time from this species. Moreover, compounds 1−5, 7, and 8 showed significant antiplatelet aggregation and compounds 1 and 6 exhibited significant vasorelaxant activities, respectively.

Romucosine (1), a novel aporphinoid alkaloid possessing a N-(methoxycarbonyl) group, along with 12 known compounds including eight isoquinoline alkaloids, anonaine (2), glaucine, purpureine, liriodenine, oxoglaucine, oxopurpureine, berberine, and tetrahydroberberine, and four lignans, yangambin, magnolin, eudesmin, and membrin, have been isolated and characterized from the fresh unripe fruits of Rollinia mucosa (Annonaceae). The structure of 1 was established by chemical and spectroscopic means.

Two novel sesquiterpenes of the furanogermacrane type, parvigemone (7) and neolitrane (8), along with six known compounds, zeylanidine (1), zeylanicine (2), linderalactone (3), pseudoneolinderane (4), linderane (5), and deacetylzeylanidine (6), have been isolated from the stems of Neolitsea parvigemma. The structures of these compounds were elucidated on the basis of spectroscopic techniques, and the structure of compound 8 was confirmed by X-ray crystallographic analysis.

Phytochemical analysis of the fruits of Annona squamosa yielded 12 known kaurane derivatives (1−11, 13) and two new kaurane diterpenoids, which have been named annosquamosin A (16β-hydroxy-17-acetoxy-ent-kauran-19-al) (12) and annosquamosin B (19-nor-ent-kaurane-4α,16β,17-triol) (14). The structures of the new compounds were established by spectral analyses and chemical evidence. Among these 14 compounds, 16β,17-dihydroxy-ent-kauran-19-oic acid (2) showed significant activity against HIV replication in H9 lymphocyte cells with an EC50 value of 0.8 μg/mL (therapeutic index >5).

A novel alkaloid, hydrachine A (3), has been isolated, along with 15 known compounds, from the roots of Hydrangea chinensis. The structure and stereochemistry of the new alkaloid 3 was determined using extensive 2D NMR data.

A novel oxazoloaporphine, artabonatine A (1), and a new 7-hydroxyaporphine, artabonatine B (2), have been isolated and characterized from the fresh unripe fruits of Artabotrys uncinatus, along with five known compounds. Structure elucidation of 1 and 2 was based on UV, IR, NMR, and MS analyses.