Sesquiterpene phenylpropanoid and sesquiterpene chromone derivatives from Ferula pallida

Four novel compounds-two sesquiterpene phenylpropanoid derivatives, pallidones G (1) and H (2), and two sesquiterpene chromone derivatives, pallidones I (3) and J (4)-have been isolated from the roots of Ferula pallida. Their structures were determined on the basis of NMR and HREIMS evidence.     

Terpenylated coumarins as SIRT1 activators isolated from Ailanthus altissima

Four new terpenylated coumarins (1-4) were isolated from the stem bark of Ailanthus altissima by bioactivity-guided fractionation using an in vitro SIRT1 deacetylation assay. Their structures were identified as (2'R,3'R)-7-(2',3'-dihydroxy-3',7'-dimethylocta-6'-enyloxy)-6,8-dimethoxycoumarin (1), 6,8-dimethoxy-7-(3',7'-dimethylocta-2',6'-dienyloxy)coumarin (2), (2'R,3'R,6'R)-7-(2',3'-dihydroxy-6',7'-epoxy-3',7'-dimethyloctaoxy)-6,8-dimethoxycoumarin (3), and (2'R,3'R,4'S,5'S)-6,8-dimethoxy-7-(3',7'-dimethyl-4',5'-epoxy-2'-hydroxyocta-6'-enyloxy)coumarin (4). Compounds 1-4 strongly enhanced SIRT1 activity in an in vitro SIRT1-NAD/NADH assay and an in vivo SIRT1-p53 luciferase assay. These compounds also increased the NAD-to-NADH ratio in HEK293 cells. The present results suggest that terpenylated coumarins from A. altissima have a direct stimulatory effect on SIRT1 deacetylation activity and may serve as lead molecules for the treatment of some age-related disorders.     

Kopetdaghins A-E, sesquiterpene derivatives from the aerial parts and the roots of Dorema kopetdaghense

Three new sesquiterpene derivatives, kopetdaghins A-C (1-3), one known prenylated coumarin (7), and two known steroid glucosides, sitosterol 3-O-glucoside and stigmasterol 3-O-glucoside, were isolated from the aerial parts of Dorema kopetdaghense. In addition, two new sesquiterpene derivatives, kopetdaghin D (4) and kopetdaghin E (5), together with kopetdaghins A-C and one known sesquiterpene coumarin (6), were isolated from the roots of the plant. The structures of these compounds were elucidated by various 1D and 2D NMR techniques as well as high-resolution positive-ion ESIMS.     

Sesquiterpene coumarins from Ferula gumosa

A new sesquiterpene coumarin, gumosin (1), two new sesquiterpene coumarin glycosides, gumosides A (2) and B (3), and 10 known compounds, namely, cauferoside (4), feselol (5), conferoside, ferilin, ferocaulidin, ligupersin A, conferol, and daucosterol, and the phenolic compounds acantrifoside E and 4-hydroxybenzoic acid 4-(6-O-sulfo)glucopyranoside, were isolated from a methanolic extract of Ferula gumosa roots. The structures of 1-3 were elucidated by spectroscopic data interpretation. The cytotoxic activity of the sesquiterpene coumarin derivatives was evaluated against a small panel of cancer cell lines.     

Biologically active sesquiterpene coumarins from Ferula species

Extracts from different species of the genus Ferula (Apiaceae) have had various biomedical applications for many centuries. Many biological features of this genus such as cytotoxicity, antibacterial, antiviral, P-glycoprotein (P-gp) inhibitory and antiinflammatory activity have been attributed to sesquiterpene coumarins; structures containing a common coumarin group and a sesquiterpene moiety. This both highlights the importance of sesquiterpene coumarins as biologically active natural products and necessitates further studies on these compounds. Taking into account the versatile biological properties of compounds isolated from Ferula and the unprecedented interest in the application of natural products as a new generation of therapeutics, the present review will discuss reports on biological activities of sesquiterpene coumarins of the genus Ferula, from 1990 onwards.     

Sesquiterpene lactones from Anthemis altissima and their anti-Helicobacter pylori activity

Seven sesquiterpene lactones, (-) sivasinolide (1), a new naturally occurring eudesmanolide (altissin, 2), desacetyl-beta-cyclopyrethrosin (3), tatridin-A (4), 1-epi-tatridin B (5), 1alpha,10beta-epoxy-6-hydroxy-1,10H-inunolide (6), and spiciformin (7), were isolated from Anthemis altissima. Also isolated were 10 known flavonoids, namely, apigenin (8), kaempferol 4'-methyl ether (9), quercetin (10), quercetin 3-methyl ether (11), isorhamnetin (12), rhamnetin (13), 6-hydroxyquercetin 3,6,4'-trimethyl ether (14), isoquercetrin (15), taxifolin (16), and eriodictyol (17), and one phenolic acid, chlorogenic acid (18). The structure and the stereochemistry of compound 2 were deduced by spectroscopic methods. The in vitro activity of the sesquiterpene lactones (1-5) against Helicobacter pylori, as well as against three Gram-positive and three Gram-negative bacteria growing aerobically, was tested using the microdilution method. Compounds 8-18 have also been tested against H. pylori.     

New cytotoxic cyclic peptides and dianthramide from Dianthus superbus

Four new cyclic peptides, dianthins C-F (1-4), and a new dianthramide, 4-methoxydianthramide B (5), were isolated from the MeOH extract of the traditional Chinese medicinal plant Dianthus superbus. The sequences of cyclic peptides 1-4 were elucidated as cyclo(Gly(1)-Pro(2)-Phe(3)-Tyr(4)-Val(5)-Ile(6)-), cyclo(Gly(1)-Ser(2)-Leu(3)-Pro(4)-Pro(5)-Ile(6)-Phe(7)-), cyclo(Gly(1)-Pro(2)-Ile(3)-Ser(4)-Phe(5)-Val(6)-), and cyclo(Gly(1)-Pro(2)-Phe(3)-Val(4)-Phe(5)-) on the basis of ESI tandem mass fragmentation analysis, chemical evidence, and extensive 2D NMR methods. The conformation of compound 1 was established as an alpha-helix by CD analysis. Furthermore, compounds 3 and 5 showed cytotoxicities toward the Hep G2 cancer cell line with IC(50) values of 2.37 and 4.08, respectively.     

Antiinflammatory constituents of Celastrus orbiculatus inhibit the NF-kappaB activation and NO production.

Two new sesquiterpene esters, 1beta,8beta-diacetoxyl-6alpha,9alpha-difuroyloxydihydro-beta-agarofuran (1) and 1beta-acetoxyl-2beta,6alpha,9alpha-trifuroyloxydihydro-beta-agarofuran (2), together with four known sesquiterpene esters (3-6), celastrol (7), and celaphanol A (8) were isolated from the roots of Celastrus orbiculatus in a search for inhibitors of NF-kappaB activation and nitric oxide production. Compound 7 was the most active, while compounds 1, 2, 4, and 8 showed moderate inhibition in both NF-kappaB activation and nitric oxide production.     

Oligosaccharide esters from the roots of Polygala arillata

Two new sucrose esters, arillatoses A (1) and B (2), and four new trisaccharide esters, arillatoses C-F (3-6), were isolated from the roots of Polygala arillata, together with four known sucrose esters, glomeratose E (7) and sibiricoses A(1) (8), A(5) (9), and A(6) (10). The structures of the new compounds were elucidated on the basis of chemical and spectroscopic evidence.     

Biotransformation of imperatorin by Aspergillus flavus

Imperatorin (1) was metabolized by Aspergillus flavus, in growth media, to give five metabolites. On the basis of their physical data, the structures of the five metabolites were elucidated as xanthotoxol (2), E-trichoclin (3), Z-trichoclin (4), E-imperatorin acid (5), and Z-imperatorin acid (6); among these, 4, 5, and 6 were characterized as new coumarins. The five metabolites 2-6 were tested for anti-hepatitis B virus activity in vitro and found to be less active than the parent compound 1.     

Sesquiterpene esters from Celastrus orbiculatus and their structure-activity relationship on the modulation of multidrug resistance.

Six new (1-6) and three known (7-9) sesquiterpene esters were isolated from the roots of Celastrus orbiculatus. The structures of the new compounds were elucidated as 1beta-acetoxy-6alpha-furoyloxy-9alpha-benzoyl oxydihydro-beta-agarofur an (1), 1beta-acetoxy-6alpha-benzoyloxy-9alpha-furoyloxydih ydro-beta-agarofur an (2), 1beta-acetoxy-6alpha, 9alpha-difuroyloxydihydro-beta-agarofuran (3), 1beta, 2beta-diacetoxy-6alpha-furoyloxy-9alpha-benzo yloxydihydro-beta-agarof uran (4), 1beta-acetoxy-2beta, 6alpha-difuroyloxy-9alpha-benzoyloxydihydro-beta -agarofuran (5), and 1beta-acetoxy-2beta,6alpha, 9alpha-tribenzoyloxydihydro-beta-agarofuran (6). Compounds 4, 5, and 7-9 were shown to be more active than verapamil in reversing vinblastine resistance in multidrug-resistant KB-V1 cells.     

Sesquiterpene lactones from Centaurea spinosa and their antibacterial and cytotoxic activities

Ten sesquiterpene lactones, 8alpha-O-(3,4-dihydroxy-2-methylenebutanoyloxy)sonchucarpolide (4-epi-malacitanolide) (1), 8alpha-O-(4-acetoxy-2-hydroxymethylbuten-2-oyloxy)-4-epi-sonchucarpolide (2), malacitanolide (3), its 4'-acetyl derivative (4), 8alpha-O-(3,4-dihydroxy-2-methylenebutanoyloxy)dehydromelitensine (5), 8alpha-O-(3,4-dihydroxy-2-methylenebutanoyloxy)-15-oxo-5,7alphaH,6betaH-eleman-1,3,11(13)-trien-6,12-olide (6), the germacranolides 8alpha-O-(4-acetoxy-2-hydroxymethylbuten-2-oyloxy)salonitenolide (7), cnicin (8), and 4'-acetylcnicin (9), and the sesquiterpene methyl 8alpha-O-(3,4-dihydroxy-2-methylenebutanoyloxy)-6alpha,15-dihydroxyelema-1,3,11(13)-trien-12-oate (10), were isolated from the aerial parts of Centaurea spinosa.Nine known flavonoids were also isolated. The structures and the stereochemistry of the new compounds 1 and 2 were deduced by spectroscopic methods. The in vitro activity of 1-10 against three Gram-positive and three Gram-negative bacteria was evaluated using a microdilution method, and their in vitro cytotoxic activity was determined against a panel of human tumor cell lines.     

Five new insecticidal sesquiterpenoids from Celastrus angulatus

Five new sesquiterpene polyol esters were isolated from the root bark of Celastrus angulatus by bioassay-guided fractionation. Their structures were determined by spectral data interpretation as 1alpha,2alpha,6beta,8beta,13-pentaacetoxy-9beta-benzoyloxy-4beta-hydroxy-beta-dihydroagarofuran (1), 1alpha,2alpha,6beta-triacetoxy-8alpha-(beta-furancarbonyloxy)-9beta-benzoyloxy-13-isobutanoyloxy-4beta-hydroxy-beta-dihydroagarofuran (2), 1alpha,2alpha,6beta-triacetoxy-8beta-isobutanoyloxy-9beta-(beta-furancarbonyloxy)-13-(alpha-methyl)butanoyloxy-4beta-hydroxy-beta-dihydroagarofuran (3), 1alpha,2alpha,6beta-triacetoxy-8alpha,13-diisobutanoyloxy-9beta-benzoyloxy-4beta-hydroxy-beta-dihydroagarofuran (4), and 1alpha,2alpha,6beta-triacetoxy-8alpha-isobutanoyloxy-9beta-benzoyloxy-13-(alpha-methyl)butanoyloxy-4beta-hydroxy-beta-dihydroagarofuran (5). Compounds 1-5 exhibited insecticidal activity against the larval of Mythimna separata.     

Caryophyllene sesquiterpenoids from a fungicolous isolate of Pestalotiopsis disseminata

Three new caryophyllene-type sesquiterpene alcohols, 6-hydroxypunctaporonin E (1), 6-hydroxypunctaporonin B (2), and 6-hydroxypunctaporonin A (3), have been isolated from cultures of the fungicolous fungus Pestalotiopsis disseminata. The structures of 1-3 were determined mainly by analysis of 1D and 2D NMR data. The structure and absolute configuration of 6-hydroxypunctaporonin E (1) was confirmed through X-ray crystallographic analysis of its mono-bromobenzoate derivative. Compounds 1 and 2 showed activity against Gram-positive bacteria.     

Phelligridins C-F: cytotoxic pyrano[4,3-c][2]benzopyran-1,6-dione and furo[3,2-c]pyran-4-one derivatives from the fungus Phellinus igniarius

Three unique pyrano[4,3-c][2]benzopyran-1,6-dione derivatives and a new furo[3,2-c]pyran-4-one, named phelligridins C-F (2-5), together with hispolon (8), (E)-4-(3,4-dihydroxyphenyl)but-3-en-2-one (9), 4-hydroxybenzaldehyde, protocatechualdehyde, syringic acid, protocatechuic acid, caffeic acid, isoergosterone, and octadecyl ferulate were isolated and identified from the ethanolic extract of Phellinus igniarius. Their structures were determined by spectroscopic methods including IR, MS, and 1D and 2D NMR experiments. The structures of the new compounds were characterized as 3-(4-hydroxystyryl)-8,9-dihydroxypyrano[4,3-c]isochromene-4-one (2), 3-(3,4-hydroxystyryl)-8,9-dihydroxypyrano[4,3-c]isochromene-4-one (3), 8,9-dihydroxy-3-[5',6'-dihydroxy-5' '-methyl-3' '-oxo-spiro[fural-2' '(3' 'H),1'-indene]-2'-yl]-1H,6H-pyrano[4,3-c][2]benzopyran-1,6-dione (4), and (3Z)-3-(3,4-dihydroxybenzylidene)-6-(3,4-dihydroxystyryl)-2,3-dihydro-2-methoxy-2-(2-oxo-propyl)furo[3,2-c]pyran-4-one (5), respectively. Some compounds including 2 and 3 showed in vitro selective cytotoxicity against a human lung cancer cell line (A549) and a liver cancer cell line (Bel7402). Possible biogenetic sequences to the formation of 1-9 are postulated.     

Chemical constituents from the aerial parts of Aster koraiensis with protein glycation and aldose reductase inhibitory activities

Two new eudesmane-type sesquiterpene glucosides, 9β-O-(E-p-hydroxycinnamoyl)-1β,6β-dihydroxy-trans-eudesm-3-en-6-O-β-D-glucopyranoside (1) and 9α-O-(E-p-hydroxycinnamoyl)-1α,6α-11-trihydroxy-trans-eudesm-3-en-6-O-β-D-glucopyranoside (2), were isolated by the activity-guidedfractionation of an EtOAc-soluble fraction from the aerial parts of Aster koraiensis. A new dihydrobenzofuran glucoside, (2R,3S)-6-acetyl-2-[1-O-(β-D-glucopyranosyl)-2-propenyl]-5-hydroxy-3-methoxy-2,3-dihydrobenzofuran (3), was also isolated, in addition to 15 known compounds. The structures of 1-3 were determined by spectroscopic data interpretation. All of the isolates were evaluated for in vitro inhibitory activity against the formation of advanced glycation end-products and rat lens aldose reductase.     

Natural and semisynthetic mammea-type isoprenylated dihydroxycoumarins uncouple cellular respiration

In an effort to identify natural product-based molecular-targeted antitumor agents, mammea-type coumarins from the tropical/subtropical plant Mammea americana were found to inhibit the activation of HIF-1 (hypoxia-inducible factor-1) in human breast and prostate tumor cells. In addition to the recently reported mammea E/BB (15), bioassay-guided fractionation of the active extract yielded 14 mammea-type coumarins including three new compounds, mammea F/BB (1), mammea F/BA (2), and mammea C/AA (3). The absolute configuration of C-1' in 1 was determined by the modified Mosher's method on a methylated derivative. These coumarins were evaluated for their effects on mitochondrial respiration, HIF-1 signaling, and tumor cell proliferation/viability. Acetylation of 1 afforded a triacetoxylated product (A-2) that inhibited HIF-1 activation with increased potency in both T47D (IC(50) 0.83 μM for hypoxia-induced) and PC-3 cells (IC(50) 0.94 μM for hypoxia-induced). Coumarins possessing a 6-prenyl-8-(3-methyloxobutyl) substituent pattern exhibited enhanced HIF-1 inhibitory effects. The O-methylated derivatives were less active at inhibiting HIF-1 and suppressing cell proliferation/viability. Mechanistic studies indicate that these compounds act as anionic protonophores that potently uncouple mitochondrial electron transport and disrupt hypoxic signaling.     

瑞香狼毒细胞培养物的化学成分研究

采用常压与减压硅胶柱色谱、半制备HPLC、Sephadex LH-20等方法,从瑞香狼毒Stellera chamaejasme细胞培养物85％乙醇提取物的乙酸乙酯部分分离纯化得到了17个化合物,依据理化性质和各种波谱技术分别鉴定为:丁香脂素(1),杜仲树脂酚(2),松脂素(3),(1R,2S,5R,6S) -2-(4-hydroxyphenyl) -6-( 3-methoxy-4- hydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane(4),表松脂酚(5),caruilignan D(6),3-羰基愈创木烷-4-烯-11,12-二醇(7),落叶松脂素(8),tetrahydro-2-( 4-hydroxy-3-methoxyphenyl) -4-[ (4-hydroxyphenyl) methyl] -3-furanmethanol(9),5′-甲氧基落叶松脂醇(10),vladinol D( 11),环(L-脯氨酸-L-缬氨酸)(12),7′-羰基马台树脂醇(13),(+) -guayarol( 14),acutissimalignanB(15),异落叶松脂素(16)以及β-谷甾醇(17).其中化合物12为环二肽类化合物,7为倍半萜类化合物.除化合物7,12与17外,其余均为木脂素类化合物.17个化合物均首次从该植物组织培养物中获得.     

Natural and synthetic 2,2-dimethylpyranocoumarins with antibacterial activity

A new efficient synthetic approach to the natural coumarins 5-hydroxyseselin (5), 5-methoxyseselin (3), and (+/-) cis-grandmarin (9) is described as well as the synthesis of some new derivatives in the 5-methoxyseselin series (10-15). The natural coumarins 7-hydroxyalloxanthyletin (6), alloxanthoxyletin (8), and dipetalolactone (7) have also been obtained as secondary products. The type of fusion of the pyrano ring in all cases has been established by 2D NMR spectroscopy. The compounds have been studied for their in vitro antibacterial activity, which has been compared with that of some previously synthesized seselin derivatives. The most active compounds were 3, 7, 8, 11, and 14. Some structure-activity relationships are discussed.     

Isolation and characterization of aphidicolin and chlamydosporol derivatives from Tolypocladium inflatum

Six new secondary metabolites including two aphidicolin analogues, inflatins A (1) and B (2), and four chlamydosporol derivatives, inflatins C-F (3-6), have been isolated from the crude extract of Tolypocladium inflatum. The structures of 1-6 were determined mainly by NMR experiments, and 4 and 5 were further confirmed by X-ray crystallography. The absolute configurations of C-16 in 1 and C-5 in 3 were deduced via the circular dichroism data of the in situ formed [Rh?(OCOCF?)?] complexes, whereas that of 4 was assigned by X-ray crystallography using Cu Kα radiation. Compounds 1 and 2 showed modest cytotoxicity against a panel of eight human tumor cell lines.