New bioactive clerodane diterpenoids from the bark of Casearia grewiifolia

Bioactivity-guided fractionation of hexane and dichloromethane extracts of the bark of Casearia grewiifolia afforded four new clerodane diterpenes, caseargrewiins A-D (1-4), and two known clerodane diterpenes, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-methoxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (5) and rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (6). The structures of 1-4 were established on the basis of the interpretation of their 1D and 2D NMR spectral data. The absolute configuration of 4 was determined by the modified Mosher's method. All compounds exhibited promising antimalarial and antimycobacterial activities but also cytotoxicity against three cancer cell lines.     

New cytotoxic clerodane diterpenoids from the leaves and twigs of Casearia membranacea

Bioassay-guided fractionation of an EtOAc-soluble extract of Casearia membranacea has resulted in the isolation of six new clerodane diterpenes, caseamembrins A-F (1-6), and a known compound, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-diacetoxy-18,19-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (7). The structures of 1-6 were established on the basis of extensive 1D and 2D NMR spectroscopic analysis. In addition, the new derivatives, 8 and 9, were prepared by acylation of 7 and 3, respectively. The isolated diterpenoids and their derivatives were tested against human prostate (PC-3) and hepatoma (Hep3B) cancer cells. Compounds 1, 3-5, and 7 exhibited cytotoxicity against both tumor cells, with IC(50) values below 3 micromicro, while compounds 2, 6, 8, and 9 were less effective.     

Cytotoxic clerodane diterpenoids from Casearia membranacea

Bioassay-guided fractionation of the EtOAc extract of Casearia membranacea leaves and twigs afforded three new clerodane diterpenes, caseamembrins M-O (1-3), and the known rel-(2S,5R,6R,8S,9S,10R,18S,19R)-2-(2-methylbutyryloxy)-6-hydroxy-18,19-di-O-acetyl-18,19-epoxycleroda-3,13(16),14-triene (4) and caseamembrin D (5). The structures of 1-3, including the relative configurations, were established by extensive NMR spectroscopic analyses. The cytotoxic activities of the isolated diterpenoids against human oral epidermoid (KB), medulla (Med), and colon (DLD-1) cancer cell lines were evaluated.     

In vivo activity of benzoyl ester clerodane diterpenoid derivatives from Dodonaea polyandra

Four new benzoyl ester clerodane diterpenoids, 15,16-epoxy-8α-(benzoyloxy)methylcleroda-3,13(16),14-trien-18-oic acid (1), 15,16-epoxy-8α-(benzoyloxy)methyl-2α-hydroxycleroda-3,13(16),14-trien-18-oic acid (2), 15,16-epoxy-8α-(benzoyloxy)methyl-2-oxocleroda-3,13(16),14-trien-18-oic acid (3), and 15,16-epoxy-2α-benzoyloxycleroda-3,13(16),14-trien-18-oic acid (4), have been isolated from the leaves and stems of Dodonaea polyandra. The anti-inflammatory activities of compounds 1, 2, and 4 were evaluated by means of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. Compounds 2 and 4 exhibited maximum inhibition of inflammation (70-76%) at doses of 0.22 and 0.9 μmol/ear, respectively. Modest activity (~45% inhibition) was maintained at nanomole/ear doses.     

Neoclerodane diterpenoids from Croton eluteria

Five new neoclerodane diterpenoids, rel-(3R,4S,5R,7R,8S,9R,10S,12R,20S)-7-acetoxy-15,16,12,20-diepoxy-3,4-dihydroxy-20-methoxyneocleroda-13(16),14-diene (1), rel-(3R,4S,5R,7R,8S,9R,10S,12R,20S)-7-acetoxy-15,16,12,20-diepoxy-3,4,20-trihydroxyneocleroda-13(16),14-diene (2), rel-(3R,4S,5S,6R,7S,8S, 9R,10S,12R,20S)-6,7-diacetoxy-3,4,15,16,12,20-triepoxy-20-hydroxyneocleroda-13(16),14-diene (3), rel-(3R,4S,5R,7R,8S,9R,10S,12R,20S)-7-acetoxy-3,4,15,16,12,20-triepoxy-20-hydroxyneocleroda-13(16),14-diene (4), and rel-(3R,4S,5R,7R,8S,9R,10S,12R,20R)-7,20-diacetoxy-3,4,15,16,12,20-triepoxyneocleroda-13(16),14-diene (5), have been isolated from the bark of Croton eluteria. The structures of the compounds 1-5 (cascarillins E-I) were determined by spectroscopic data interpretation.     

Cytotoxic dolabellane diterpenes from the Formosan soft coral Clavularia inflata

Six new cytotoxic dolabellane diterpenes, (1R,12R)-dolabella-4(16),7,10-triene-3,13-dione (1), (1R*,7R*,8S*,12R*)-dolabella-4(16),10-diene-7,8-epoxy- 3,13-dione (2), (1R*,10R*,11S*,12R*)-dolabella-4(16),7-diene-10,11-epoxy-3,13-dione (3), (1R)-dolabella-4(16),7,11(12)-triene-3,13-dione (4), (1R*,3R*)-3-hydroxydolabella-4(16),7,11(12)-triene-3,13-dione (5), and (1R*,7R*)-7-hydroperoxydolabella-4(16),8(17),11(12)-triene-3,13-dione (6), have been isolated from the Formosan soft coral Clavularia inflata. The structures of compounds 1-6 were determined by 1D and 2D spectral analysis, and their cytotoxicity against selected cancer cells was measured in vitro.     

Antimicrobial activity of various parts of Polyalthia longifolia var. pendula: isolation of active principles from the leaves and the berries

Methanol extracts of leaves, stem, twigs, green berries, flowers, roots, root-wood and root-bark of Polyalthia longifolia var. pendula, were tested for their antibacterial and antifungal potentials. Bioassay monitored isolation work on the methanol extract of leaves and berries which possess promising antibacterial activity led to the isolation of seven clerodane diterpenoids, 16(R and S)-hydroxy-cleroda-3,13(14)Z-dien-15,16-olide (1), 16-oxo-cleroda-3,13(14)E-dien-15-oic acid (2), methyl-16-oxo-cleroda-3,13(14)E-dien-15-oate (3), 2-oxo-kolavenic acid (4), 16 (R and S)-hydroxy-cleroda-3,13(14)Z-dien-15,16-olide-2-one (5), (4-->2)-abeo-16(R and S)-hydroxy-cleroda-2,13(14)Z-dien-15,16-olide-3-al (6), 3beta,16alpha-dihydroxy-cleroda-4(18), 13(14)Z-dien-15,16-olide (7), while kolavenic acid (8) and solidagonal acid (9) were obtained from the root-wood. Diterpenoids 1 and 8 were also obtained from the root-bark. It is the first report of the isolation of 7 and 9 from this source, and clerodane 3 was obtained as a natural product for the first time. Clerodanes 1, 2, 5, 6 and 7 were found to be active antimicrobial agents with MIC values ranging between 7.8 and 500 microg/mL. Diterpenoid 1 emerged as the most active antimicrobial agent. The acetyl derivative (10) of 1 and the methyl derivative (3) of 2 were found to be less active than the parent compounds. A complex of allantoin was also obtained from the berries, which on hydrolysis furnished pure allantoin (11).     

Tetranorclerodanes and clerodane-type diterpene glycosides from Dicranopteris dichotoma

The acetone extract of Dicranopteris dichotoma afforded two new tetranorclerodanes, 18-hydroxyaylthonic acid (1) and 18-oxo-aylthonic acid (2), and four new clerodane-type diterpene glycosides, (6S,13S)-6-O-[6-O-acetyl-beta-d-glucopyranosyl-(1-->4)-alpha-l-rhamnopyranosyl]cleroda-3,14-dien-13-ol (3), (6S,13S)-6-O-[4-O-acetyl-beta-d-glucopyranosyl-(1-->4)-alpha-l-rhamnopyranosyl]cleroda-3,14-dien-13-ol (4), 6-O-[6-O-acetyl-beta-d-glucopyranos-yl-(1-->4)-alpha-l-rhamnopyranosyl]-(13E)-cleroda-3,13-dien-15-ol (5), and 6-O-[beta-d-glucopyranosyl]-(1-->4)-alpha-l-rhamnopyranosyl-(13E)-cleroda-3,13-dien-15-ol (6), together with two known compounds, aylthonic acid (7) and (6S,13S)-cleroda-3,14-diene-6,13-diol (8). The structures of these new compounds were established by a combination of 1D and 2D NMR techniques, MS, and acid hydrolysis. Compound 8 showed modest anti-HIV-1 activity.     

ent-Kaurane diterpenoids from Isodon japonicus

Five ent-kaurane diterpenoids, 6beta,7beta,14beta-trihydroxy-1alpha,19-diacetoxy-7alpha,20-epoxy- ent-kaur-16-en-15-one (1), 1alpha,6beta,7beta-trihydroxy-11alpha,19-diacetoxy-7alpha,20-epoxy-ent-kaur-16-en-15-one (2), 6-hydroxy-1alpha,19-diacetoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide (3), 19-hydroxy-1alpha,6-diacetoxy-6,7-seco- ent-kaur-16-en-15-one-7,20-olide (4), and 6-aldehyde-1alpha,19-diacetoxy-6,7-seco- ent-kaur-16-en-15-one-7,20-olide (5), along with 10 known ent-kaurane diterpenoids, pseurata C (6), longikaurin C (7), effusanin C (8), longikaurin B (9), longikaurin D (10), effusanin D (11), excisanin B (12), lasiokaurin (13), megathyrin A (14), and loxothyrin A (15), were isolated from the aerial parts of Isodon japonicus. Their structures were determined on the basis of spectroscopic (1D-, 2D-NMR and MS) and chemical evidence. The isolates were evaluated for their inhibitory effects on LPS-induced production of nitric oxide in murine macrophage RAW264.7 cells.     

Cytotoxic constituents from the fruiting branches of Callicarpa americana collected in southern Florida

Bioassay-guided fractionation of the combined fruits, leaves, and twigs (fruiting branches) of Callicarpa americana, collected from a plot in a forested area in southern Florida, led to the isolation of six new clerodane diterpenes (1-6) and eight known compounds. The structures of 1-6 [12(S),16xi-dihydroxycleroda-3,13-dien-15,16-olide (1), 12(S)-hydroxy-16xi-methoxycleroda-3,13-dien-15,16-olide (2), 12(S)-hydroxycleroda-3,13-dien-15,16-olide (3), 16xi-hydroxycleroda-3,11(E),13-trien-15,16-olide (4), 3beta,12(S)-dihydroxycleroda-4(18),13-dien-15,16-olide (5), and 12(S)-hydroxycleroda-3,13-dien-16,15-olide (6)] were elucidated by interpretation of spectroscopic data and chemical methods. The absolute configuration at C-12 in 1 and 3 was ascertained using the Mosher ester technique. The cytotoxicity of all isolates was tested against a panel of human cancer cell lines, and compounds 1, 4, and 6, and the known compounds genkwanin, 16xi-hydroxycleroda-3,13-dien-15,16-olide, and 2-formyl-16xi-hydroxy-3-A-norcleroda-2,13-dien-15,16-olide were active (ED50 <5 microg/mL). However, 1 was found to be inactive against human cancer cells implanted in mice using a hollow-fiber tumor model.     

Microbial transformation and butyrylcholinesterase inhibitory activity of (-)-caryophyllene oxide and its derivatives

Microbial transformation of the sesquiterpene (-)-caryophyllene oxide (1) [(1R,4R,5R,9S)-4,5-epoxycaryophyllan-8(13)-ene] by a number of fungi, using a standard two-stage fermentation technique, has afforded as products (1R,4R,5R,9S)-4,5-dihydroxycaryophyllan-8(13)-ene (2), (1S,4R,5R,8S,9S)-clovane-5,9-diol (3), (1R,4R,5R,9S,11R)-4,5-epoxycaryophyllan-8(13)-en-15-ol (4), (1R,4R,5R,9S,11S)-4,5-epoxycaryophyllan-8(13)-en-14-ol (5), (1R,2S,4R,5R,9S)-4,5-epoxy-13-norcaryophyllan-8-one (6), (1R,4R,5R,8S,9S)-4,5-epoxycaryophyllan-13-ol (7), (1R,4R,5R,8S, 9S,13S)-caryolane-5,8,13-triol (8), (1R,3R,4R,5R,8S,9S)-4,5-epoxycaryophyllan-3,13-diol (9), and (1S,4R,5R,8S,9S)-clovane-5,9,12-triol (10). Metabolites 6 and 8-10 were found to be new compounds, as deduced on the basis of spectroscopic techniques. Compounds 1-10 were evaluated for butyrylcholinesterase inhibitory activity, and compound 5 exhibited an IC50 value of 10.9 +/- 0.2 microM.     

Neoclerodane diterpenoids from Scutellaria caerulea.

Five new neoclerodane diterpenoids have been isolated from Scutellaria caerulea: (11S*)-6 alpha-acetoxy-7 beta,11-diisobutiryloxy-1 beta,8 beta-dihydroxy-4(18),13-neoclerodadien-15,16-olide (scuterulein A) (1); (13R*)-1 beta-6 alpha-7 beta-triacetoxy-11 beta-benzoyloxy-8 beta,13-epoxy-4(18)-neocleroden-15,16-olide (scuterulein B) (2); (11S*)-1 beta,6 alpha,11-triacetoxy-7 beta-isobutiryloxy-8 beta-hydroxy-4(18),13-neoclerodadien-15,16-olide (scuterulein C) (3); (11S*)-6 alpha,11-diacetoxy-7 beta-isobutiryloxy-1 beta,8 beta-dihydroxy-4(18),13-neoclerodadien-15,16-olide (deacetyl scuterulein C) (4), and (11E)-6 alpha-acetoxy-7 beta-isobutiryloxy-1 beta,8 beta-dihydroxy-4(18),11,13-neoclerodatrien-15,16-olide (scuterulein D) (5). Structures were established by spectroscopic and chemical methods. An X-ray analysis was carried out on scuterulein B (2).     

毛叶香茶菜中的二萜化合物

目的：对河南产毛叶香茶菜化学成分进行研究。方法：运用各种色谱技术和波谱分析对其化学成分进行分离鉴定。结果：分离鉴定了20个二萜化合物。结论：化合物1—3为三个新的对映-贝壳杉烷二萜类化合物，结构分别为7β，15β，16β—三羟基—6β，17β—二乙酰氧基—7α，20-环氧—对映—贝壳衫烷(1)、16（S)—6β，11α，17β—三羟基-6，20-环氧—1α，7β—内酯—6，7—断裂—对映—贝壳杉-15酮(2)和6α，11α—二海基—1α—乙酰氧基—7，20内酯—6，7—断裂—对映—贝壳杉—16—烯—15—酮(3)，依次命名为毛叶香茶菜丙素、丁素和戊素；化合物4和5为—对新化合物，其结构为3α，15α，1β6，17β，18β—五羟基。对映—松香—7(8)—烯的丙酮化物，其丙酮化缩合部分互为对映体，分别命名为毛叶香茶菜庚素(4)和辛素(5)。     

New acyclic sesquiterpenes and norsesquiterpenes from the Caribbean Gorgonian Plexaurella grisea

The gorgonian Plexaurella grisea from Punta Cana, Dominican Republic, contains five new acyclic sesquiterpenes, (3E,5E)-3,7,11-trimethyl-9-oxododeca-1,3,5-triene (3), (3Z,5E)-3,7,11-trimethyl-9-oxododeca-1,3,5-triene (4), (3E)-6-acetoxy-3,11-dimethyl-7-methylidendodeca-1,3,10-triene (5), (3E,5E)-7-hydroxy-3,7,11-trimethyldodeca-1,3,5,10-tetraene (6), and (3E,5E,9E)-8,11-diacetoxy-3,7,11-trimethyldodeca-1,3,5,9-tetraene (7), and two new linear norsesquiterpenes, (2E,4E,7Z)-2,6,10-trimethylundeca-2,4,7,9-tetraenal (8) and (2E,4E)-2,6,10-trimethylundeca-2,4,9-trienal (9), in addition to the known compounds 1, 2, and 10. The structures of the new compounds 3-9 were elucidated by interpretation of spectroscopic data. In general, the new compounds are mildly cytotoxic against tumor cell lines, and although norsesquiterpene 8 was inactive, norsesquiterpene 9 exhibited the greatest and selective activity against the P-388 tumor cell line.     

Terpenoids and a diarylheptanoid from Zingiber ottensii

Four new terpenoids and a diarylheptanoid were isolated together with 16 known compounds from rhizomes of Zingiber ottensii. The structures of the new compounds were determined to be 1,10,10-trimethylbicyclo[7,4,0]tridecane-3,6-dione (1), (E)-14-hydroxy-15-norlabda-8(17),12-dien-16-al (2), (E)-labda-8(17),12,14-trien-15(16)-olide (3), (E)-14,15,16-trinorlabda-8(17),11-dien-13-oic acid (4), and rel-(3R,5S)-3,5-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3, 4-dihydroxyphenyl)heptane (5) by spectroscopic evidence.     

Antitubercular chromones and flavonoids from Pisonia aculeata

Three new chromones, pisonins A (1), B (2), and D (4), two new flavonoids, pisonivanone [(2S)-5,7,2'-trihydroxy-8-methylflavanone] (7) and pisonivanol [(2R,3R)-3,7-dihydroxy-5,6-dimethoxyflavanone] (8), one new isoflavonoid, pisonianone (5,7,2'-trihydroxy-6-methoxy-8-methylisoflavone) (9), and five compounds first isolated from nature, namely, pisonins C (3), E (5), and F (6), pisoniamide (10), and pisonolic acid (11), together with 18 known compounds have been isolated from the methanol extract of the combined stem and root of Pisonia aculeata. Among these isolates, 2, 7, 14, 16, and 19 exhibited antitubercular activities (MICs≤50.0 μg/mL) against Mycobacterium tuberculosis H37Rv in vitro.     

Cytotoxic xenicane diterpenes from the brown alga Padina pavonia (L.) Gaill

Column chromatography of the hexane fraction of a methanol extract of Padina pavonia (L.) Gaill. collected from the Red Sea at Hurghada, Egypt yielded 18,19-epoxyxenic-19-methoxy-18-hydroxy-4-acetoxy-6,9,13-triene (1) and 18,19-epoxyxenic-18,19-dimethoxy-4-hydroxy-6,9,13-triene (2). The isolated compounds have various antitumor activities against lung carcinoma (H460) and liver carcinoma (HepG2) human cell lines (in vitro).     

Cembrane diterpenes from the southern African soft coral Cladiella kashmani

Two known cembrane diterpenes, flaccidoxide (1) and (1Z,3E,7E,11S, 12S,14S)-11,12-epoxy cembra-1,3,7-trien-14-ol (2), and the new cembrane diterpene flaccidoxide-13-acetate (3) were isolated from specimens of Cladiella kashmani collected off Ponto do Oura, Mozambique. The modified Mosher's method established the previously unassigned absolute configuration of 1 as (1Z,3E,7E,11S,12S,13S, 14R)-14-acetoxy-11,12-epoxy cembra-1,3,7-trien-13-ol. Acetylation of 1 yielded 3 and thus confirmed the structure of 3 as (1Z,3E,7E,11S, 12R,13S,14R)-13,14-diacetoxy-11,12-epoxy cembra-1,3,7-triene. All three diterpenes were toxic to the brine shrimp Artemia salina.     

Seco-prezizaane-type sesquiterpenes and an abietane-type diterpene from Illicium minwanense

A methanol extract of the pericarps of Illicium minwanense afforded seven new seco-prezizaane-type sesquiterpenes (2-8) and a new abietane-type diterpene (9), together with six previously known compounds (1 and 10-14). The structures of the new compounds, (1S)- and (1R)-minwanenone (2 and 3), 1alpha-hydroxy-6-deoxypseudoanisatin (4), (2S)-hydroxy-6-deoxypseudoanisatin (5), 3-oxopseudoanisatin (6), (3S,6R)-4,7-epoxy-6-deoxypseudoanisatin (7), 7-O-methylpseudomajucin (8), and (+)-8,11,13,15-abietatetraene (9), were elucidated by spectroscopic data analysis and chemical transformations. The absolute configurations of 1 and 5 were established by X-ray crystallographic analysis of their p-bromobenzoyl derivatives.     

Nasimaluns A and B: neo-clerodane diterpenoids from barringtonia racemosa

An ethanolic extract of the roots of Barringtonia racemosa afforded two novel neo-clerodane-type diterpenoids, methyl-15, 16-epoxy-12-oxo-3,13(16),14-neo-clerodatrien-18, 19-olide-17-carboxylate (nasimalun A, 1) and dimethyl-15,16-epoxy-3, 13(16),14-neo-clerodatrien-17,18-dicarboxylate (17-carboxymethylhardwickiic acid methyl ester, nasimalun B, 2) by NMR and MS analyses and by comparison of their spectral data with related compunds. The relative stereochemistry of the asymmetric centers in 1 and 2 was determined by selective 1D NOESY experiments.