Sacculatane diterpenoids from axenic cultures of the liverwort Fossombronia wondraczekii

Five new sacculatane diterpenoids, 17,18-epoxy-7-sacculaten-12,11-olide, 7,17-sacculatadien-11,12-olide, 11beta,12-epoxy-7,17-sacculatadien-11alpha-ol, 1beta-acetoxy-11beta,12-epoxy-7,17-sacculatadien-11alpha-ol and 1beta,15xi-diacetoxy-11,12-epoxy-8(12),9(11),17-sacculatatriene along with sacculatal and sacculatanolide have been isolated from axenic cultures of the liverwort Fossombronia wondraczekii and their structures assigned on the basis of their spectroscopical properties.     

ent-Clerodane diterpenes and other constituents from the liverwort Adelanthus lindenbergianus (Lehm.) Mitt

Eleven ent-clerodanes, 13-hydroxy-cis-ent-cleroda-3,14-diene, 15-hydroxy-cis-ent-cleroda-3,13(E)-diene, 1beta,12:15,16-diepoxy-cis-ent-cleroda-13(16),14-dien-18alpha,6alpha-olide, 8beta,12:15, 16-diepoxy-cis-ent-cleroda-13(16),14-dien-18alpha,6alpha-olide, 1beta,16:15,16-diepoxy-cis-ent-cleroda-12,14-dien-18alpha,6alpha-olide, 7beta,12:8beta,12-diepoxy-15-hydroxy-cis-ent-cleroda-13-en-16,15:18alpha,6alpha-diolide, 7beta,12:8beta,12-diepoxy-16-hydroxy-cis-ent-cleroda-13-en-15,16:18alpha,6alpha-diolide, 1alpha-acetoxy-8beta,12-epoxy-15-hydroxy-cis-ent-cleroda-13-en-16,15:18alpha,6alpha-diolide, 1beta,12-epoxy-16-hydroxy-cis-ent-cleroda-13-en-15,16:18alpha,6alpha-diolide, 8beta,12-epoxy-15-hydroxy-trans-cleroda-13-en-16,15:18alpha,6alpha-diolide, 8beta,12-epoxy-16-hydroxy-trans-cleroda-13-en-15,16:18alpha,6alpha-diolide along with the known clerodane diterpenes anastreptin and orcadensin have been isolated from the liverwort Adelanthus lindenbergianus (Lehm.) Mitt. Furthermore, three eudesmane sesquiterpenes together with the known (-)-1beta,10-epoxyaristolan, 3,4-seco-4(23),20(29)-lupadien-3,28-dicarboxylic acid dimethyl ester and two acetophenone derivatives were identified by spectroscopic methods, essentially MS and NMR experiments.     

Microbial transformation of neoandrographolide by Mucor spinosus (AS 3.2450)

Microbial transformation of neoandrographolide (1), was performed by Mucor spinosus (AS 3.2450). Ten metabolites were obtained and identified as 14-deoxyandrographolide (2), 17,19-dihydroxy-8,13-ent-labdadien-16,15-olide (3), 3,14-dideoxyandrographolide (4), 7β-hydroxy-3,14-dideoxyandrographolide (5), 17,19-dihydroxy-7,13-ent-labdadien-16,15-olide (6), 8(17),13-ent-labdadien-16,15-olid-19-oic acid (7), 8α,17β-epoxy-3,14-dideoxyandrographolide (8), 8β,17,19-trihydroxy-ent-labd-13-en-16, 15-olide (9), phlogantholide-A (10), 19-[(β-d-glucopyranosyl)oxy]-19-oxo-ent-labda-8(17),13-dien-16,15-olide (11) by spectroscopic and chemical means. Among them, products 3, 5, 6, 8 and 9 were characterized as new compounds. The inhibitory effects of compounds 1–11 on nitric oxide production in lipopolysaccharide-activated macrophages were evaluated and their preliminary structure–activity relationships (SAR) were discussed.     

New neutral diterpenes from southern pine tall oil

Five new diterpene natural products isolated from southern pine (Pinus spp.) tall oil were characterized as 8(14),15-pimaradiene-3β,18-diol, 19-hydroxy-15,16-dinorlabd-8(17)-en-13-one, 8,13β-epoxy-14-labden-6α-ol, 8,11, 13-abietatriene-15,18-diol and 9,10-secoabieta-8,11,13-trien-18,10-olide.     

ent-Labdane glycosides from the aquatic plant Potamogeton lucens and analytical evaluation of the lipophilic extract constituents of various Potamogeton species

Two new ent-labdane glycosides, one known furano-ent-labdane and a new hydroxylated fatty acid were isolated from the dichloromethane extract of the freshwater aquatic plant Potamogeton lucens. The new compounds were assigned the structures of beta-d-glucopyranosyl-8(17),13-ent-labdadien-16,15-olid-18-oate, 18-beta-d-glucopyranosyloxy-8(17),13-ent-labdadien-16,15-olide and 13(R)-hydroxy-octadeca-(9Z,11E,15Z)-trien-oic acid by spectroscopic means. The algicidal activity of these compounds was tested against Raphidocelis subcapitata. Based on our previous study of Potamogeton pectinatus, other constituents were identified in P. lucens by LC-UV-MS, LC-NMR and GC-MS. The lipophilic extract profiles of both species are presented. Two other species, Potamogeton perfoliatus and P. crispus, were also investigated by analytical comparison of their non-polar extracts. The distribution of ent-labdanes characterized in Potamogeton is summarized.     

Clerodane and labdane diterpenoids from Nuxia sphaerocephala

Seven diterpenoids including four clerodane and three labdane derivatives, (13S)-ent-7beta-hydroxy-3-cleroden-15-oic acid (1), ent-7beta-hydroxy-2-oxo-3-cleroden-15-oic acid (2), ent-2,7-dioxo-3-clero-den-15-oic acid (3), ent-18-(E)-caffeoyloxy-7beta-hydroxy-3-cleroden-15-oic acid (4) (13S)-ent-18-(E)-coumaroyloxy-8(17)-labden-15-oic acid (5), ent-18-(E)-caffeoyloxy-8(17)-labden-15-oic acid (6), ent-15-(E)-caffeoyloxy-8(17)-labden-18-oic acid (7), have been isolated from an ethyl acetate extract of the leaves of Nuxia sphaerocephala, together with 17 known compounds. 3-Oxolup-20(29)-en-30-al (3-oxolupenal) (8) and 3beta-hydroxylup-20(29)-en-30-al (3beta-hydroxy-lupenal) (9) showed the best inhibitory activity against Plasmodium falciparum with the IC(50) values between 1.55 and 4.67 microg/ml in vitro, respectively. The structure and the relative stereochemistry of the compounds were established on the basis of their spectroscopic properties. The absolute configuration at C-13 of 1 and 5 was determined by the PGME amide procedure.     

Antialgal furano-diterpenes from Potamogeton natans L

Six furano-ent-labdanes, 19-acetoxy-15,16-epoxy-8(17),13(16),14-ent-labdatrien-20-al, 15,16-epoxy-12-oxo-8(17),13(16),14-ent-labdatrien-20,19-olide, 12(S)-hydroxy-15,16-epoxy-8(17),13(16),14-ent-labdatrien-20,19-olide, 10alpha,19-dihydroxy-15,16-epoxy-8(17),13(16),14-nor-ent-labdatriene, 19,20-dihydroxy-15,16-epoxy-8(17),13(16),14-ent-labdatriene, 15,16-epoxy-12-oxo-8(17),13(16),14-ent-labdatrien-19,20-olide, were isolated, together with the known potamogetonin, from the aquatic plant Potamogeton natans. Their structures were determined on the basis of their chemical and spectral data. The compounds showed in vitro phytotoxicity against Raphidocelis subcapitata, a microalga used in aquatic tests.     

Flavonoids from Andrographis lineata

Three flavonoids, 5,7,2',3',4'-pentamethoxyflavone (1), 2'-hydroxy-2,4',6'-tri methoxychalcone (2) and dihydroskullcapflavone I (3), together with 17,19,20-trihydroxy-5beta, 8alpha H, 9beta H,10alpha-labd-13-en-16,15-olactone (4), a known diterpenoid and six known flavonoids, 5-hydroxy-7,8-dimethoxyflavanone (5), 5-hydroxy-7,8,2',3',4'-pentamethoxyflavone (6), 5,2'-dihydroxy-7-methoxyflavanone (7), 5,2'-dihydroxy-7,8-dimethoxyflavone (8), 5,2'-dihydroxy-7-methoxyflavone (9) and 5,2'-dihydroxy-7-methoxyflavone 2'-O-beta-D-glucopyranoside (10) were isolated from the whole plant of Andrographis lineata. The structures of these compounds were elucidated on the basis of spectral and chemical studies.     

Humirianthenolides,new degraded diterpenoids from Humirianthera rupestris

The tuber of Humirianthera rupestris (Icacinaceae) contains the degraded diterpenoids 3β,20-epoxy-30α- hydroxy- 14-oxo-9β-podocarpan-19,6β-olide (humirianthenolide A), 3β,20-epoxy-3α,14α-dihydroxy-9β-podocarpan-19,6β- olide (humirianthenolide B), 3β,20; 16,14-diepoxy-3α-hydroxy-17-nor-15-oxo-9β-abiet-13-en-19,6β-olide (humirianthenolide C), 3β,20-epoxy-3α,14-dihydroxy-13-oxo-9β-podocarp-8(14)-en-19,6β-olide (humirianthenolide D), 3β,20-epoxy-3α-hidroxy-14-oxo-8α,9β-podocarpan-19,6β-olide (humirianthenolide E) and 3β,20-epoxy-3α,14β- dihydroxy-8α,9β-podocarpan-19,6β-olide (humirianthenolide F). ¹H NMR and ¹³C NMR spectroscopy were efrective for the determination of the humirianthenolide structures.     

Geranylated flavanones from the secretion on the surface of the immature fruits of Paulownia tomentosa

Chemical investigation of the methanol extract of the viscous secretion on the surface of immature fruits of Paulownia tomentosa furnished nine geranylated flavanones, 6-geranyl-5,7-dihydroxy-3',4'-dimethoxyflavanone (1), 6-geranyl-3',5,7-trihydroxy-4'-methoxyflavanone (2), 6-geranyl-4',5,7-trihydroxy-3',5'-dimethoxyflavanone (3), 6-geranyl-4',5,5',7-tetrahydroxy-3'-methoxyflavanone (4), 6-geranyl-3,3',5,7-tetrahydroxy-4'-methoxyflavanone (5), 4',5,5',7-tetrahydroxy-6-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]-3'-methoxyflavanone (6), 3,3',4',5,7-pentahydroxy-6-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]flavanone (7), 3,3',4',5,7-pentahydroxy-6-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]flavanone (8), and 3,4',5,5',7-pentahydroxy-3'-methoxy-6-(3-methyl-2-butenyl)flavanone (9), along with six known geranylated flavanones. Among these, compounds 4, 6-9 and the known 6-geranyl-3',4',5,7-tetraahydroxyflavanone (diplacone), 6-geranyl-3,3',4',5,7-pentahydroxyflavanone (diplacol) and 3',4',5,7-pentahydroxy-6-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]flavanone showed potent radical scavenging effects towards DPPH radicals.     

Diterpenoids from the pericarp of Platycladus orientalis

Eight labdane-type diterpenes, 7beta,13S-dihydroxylabda-8(17),14-dien-19-oic acid (1), 12R,15-dihydroxylabda-8(17),13E-dien-19-oic acid (3c), 12R,15-dihydroxylabda-8(17),13Z-dien-19-oic acid (3d), 12R,13R,14S-trihydroxylabda-12,15-epoxy-8(17)-en-19-oic acid (4a), 12S,13S,14R-trihydroxylabda-12,15-epoxy-8(17)-en-19-oic acid (4b), 15-hydroxy-12-oxolabda-8(17),13E-dien-19-oic acid (5), 14R,15-dihydroxylabda-8(17),12Z-dien-19-oic acid (7a) and 14S,15-dihydroxylabda-8(17),12Z-dien-19-oic acid (7b), along with 20 known diterpenoids, were isolated from the pericarp of Platycladus orientalis. Their structures were unambiguously elucidated by NMR spectroscopic and single crystal X-ray diffraction analyses, as well as via chemical correlation conversion. NMR spectroscopic data of known isomers 8c and 8d were reported as a supplement to existing data.     

Guaianolide sesquiterpenes from Pulicaria crispa (Forssk.) Oliv

A phytochemical study of the asteraceous herb Pulicaria crispa (Forssk.) Oliv. resulted in the characterisation of three guaianolide sesquiterpenes, 2alpha,4alpha-dihydroxy-7alphaH,8alphaH,10alphaH-guaia-1(5),11(13)-dien-8beta,12-olide (1), 1alpha,2alpha-epoxy-4beta-hydroxy-5alphaH,7alphaH,8alphaH,10alphaH-guaia-11(13)-en-8beta,12-olide (2) and 5,10-epi-2,3-dihydroaromatin (3). The structures were assigned on the basis of extensive 1 and 2D NMR experiments. Compound 3 exhibited weak antimycobacterial activity against Mycobacterium phlei with a minimum inhibitory concentration of 0.52 mM and cytotoxicity (IC50 of 5.8+/-0.2 microM) in a human bladder carcinoma cell line, EJ-138.     

Resin acids of Pinus resinosa needles

The principal resin acids in the needles of Pinus resinosa are the labdane diterpenes, the new 8,13-epoxy-14-labden-19-oic acid (epimanoyl oxide acid), 8,13β-epoxy-14-labden-19-oic acid (manoyl oxide acid), 8(17),E-12,14-labdatrien-19-oic acid (communic acid) and 15-oxo-8(17)-labden-19-oic acid (imbricataloic acid). A survey of needles from representative populations of P. resinosa showed a limited variability in resin acid composition consistent with the uniformity of other traits. The composition of needle resin acids for putative P. nigra x resinosa hybrids strongly suggests the improbability of P. resinosa as the pollen parent.     

Glechomanolides and eudesmanolides from Smyrnium perfoliatum

In addition to five known sesquiterpenoids, six new compounds were isolated from Smyrnium perfoliatum. The new compounds were 1β-acetoxy-eudesma-3,7(11),8-trien-8,12-olide, 1β-acetoxyeudesma-4(15),7(11),8-trien-8,12-olide, 1β-10α;4α,5β-diepoxy-8β-isobutoxy-glechomanolide, 1β, 10α;4α,5β-diepoxy-8α-isobutoxy-glechomanolide, 1β,4α-dihydroxy-2α,3α-epoxy-eudesma-7(11),8-dien-8,12-olide, 1β,4α-dihydroxy-2α,3α-epoxy-8β-methoxy-eudesma-7(11)-en-8α,12-olide.     

Diterpenoids from Isodon enanderianus

Four ent-kauranoids, 6-epiangustifolin and enanderinanins F-H, as well as 11 known ent-kaurane diterpenoids, macrocalin B, xerophilusin A, trichorabdal A, trichorabdal B, effusin, angustifolin, longikaurin D, longikaurin F, enanderinanin B, xerophilusin G and shikokianin were isolated from the aerial parts of Isodon enanderianus. The new diterpenoids were identified as 6-epiangustifolin (11alpha-hydroxy-6alpha-methoxy-6,19-epoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide), enanderinanin F (19-acetoxy-6,20:6,11beta-diepoxy-6,7-seco-ent-kaur-16-en-15-one-1beta,7-olide), enanderinanin G (1beta,6beta,7beta-trihydroxy-19-acetoxy-16beta-methoxymethyl-7alpha,20-epoxy-ent-kaur-15-one) and enanderinanin H (6beta,7beta,14beta-trihydroxy-1alpha,11beta-acetonide-7alpha,20-epoxy-ent-kaur-16-en-15-one), respectively, on the basis of spectral data, especially by 2D NMR techniques. 6-Epiangustifolin showed significant cytotoxic activity against K562 cell.     

Diterpenoids and triterpenoids from Euphorbia guyoniana

Two new compounds with tigliane and cycloartane skeletons: 4,12-dideoxy(4alpha)phorbol-13-hexadecanoate (1) and 24-methylenecycloartane-3,28-diol (2), respectively, in addition of four known diterpenoids and 13 triterpenoids: 3-benzoyloxy-5,15-diacetoxy-9,14-dioxojatropha-6(17),11-diene (4), ent-abieta-8(14),13(15)-dien-16,12-olide (5), ent-8alpha,14alpha-epoxyabieta-11,13(15)-dien-16,12-olide (6), ent-3-hydroxyatis-16(17)-ene-2,14-dione (7), 3beta-hydroxytaraxer-14-en-28-oic acid (8), beta-sitosteryl-3beta-glucopyranoside-6'-O-palmitate (9), multiflorenyl acetate (10), multiflorenyl palmitate (11), peplusol (12), 24-methylenecycloartanol (3), lanosterol (13), euferol (14), butyrospermol (15), cycloartenol (16), obtusifoliol (17), cycloeucalenol (18) and beta-sitosterol (19), were isolated from the roots of Euphorbia guyoniana. Their structures were established on the basis of physical and spectroscopic analysis, including 1D and 2D homo- and heteronuclear NMR experiments (COSY, HSQC, HMBC and NOESY) and by comparison with the literature data.     

Five diterpenoids (agallochins A-E) from the mangrove plant Excoecaria agallocha Linn

Chemical examination of the hexane extract of the roots of Excoecaria agallocha Linn collected from the Godavari estuary resulted in the isolation of altogether eleven diterpenoids of which five (1-5) are new. The structures of the new diterpenoids have been elucidated by a study of their physical and spectral (UV, IR, 1H, 13C, DEPT, 1H-1H COSY, NOESY, HMQC, HMBC and MASS) data as 3-oxo-ent-13epi-8(13)-epoxy-15-chloro-14-hydroxylabdane (1), ent-15-chloro-13,14-dihydroxylabd-8(9)-en-3-one (2), ent-15-chloro-labd-8(9)ene-3alpha,13,14-triol (3), ent-11beta-hydroxy-8(14),15-isopimaradien-3-one (4), 8,13-epoxy-3-nor-2,3-seco-14-epilabden-2,4-olide (5). The six known diterpenoids have been characterised respectively as ent-3-oxo-13-epi-manoyl oxide (6), ent-3beta-hydroxy-13-epi-manoyl oxide (7), (13R,14S)-ent-8alpha,13;14,15-diepoxy-13-epi-labdan-3-one (8), ent-16-hydroxy-3-oxo-13-epimanoyl oxide (9), ent-15-hydroxylabda-8(17),13E-dien-3-one (10), labda-8(17),13E-diene-3beta,15-diol (11) by a comparative study of their spectral data with the literature values.     

Labdane diterpenoids from Cistus ladaniferus

Three new diterpenic acids have been isolated from Cistus ladaniferus: 6,8(17) labdadien-15-oic, 7-oxo-8-labden-15-oic and 6β-acetoxy-7-oxo-8-labden-15-oic acids, beside labdanolic, 6-oxocativic,7α-hydroxy-8(17)-labden-15-oic, 8α-methoxy-labda-15-oic and 8α-hydroxy-13(E)-labden-15-oic acids.     

Oleanane-type triterpenes of Embelia schimperi leaves

An investigation of an ethyl acetate extract of Embelia schimperi leaves has led to the isolation of 10 oleanane-type triterpenes characterized as 3beta,16alpha-di-O-acetyl-13beta, 28-epoxyoleanane (1), 3beta-acetyl-16-oxo-13beta, 28-epoxyoleanane (2), 3beta-acetyl-16alpha-hydroxy-13beta, 28-epoxyoleanane (3), 3beta-acetyl-16alpha-hydroxyoleanane-13beta, 28-olide (4), 3beta-acetyl-28-hydroxy-16-oxo-12-oleanene (5), 3beta, 28-di-O-acetyl-16alpha-hydroxy-12-oleanene (6), 3beta-acetyl-11alpha, 28-dihydroxy-16-oxo-12-oleanene (7), 3beta, 11alpha, 16alpha, 28-tetrahydroxy-12-oleanene (8), 3beta-acetyl-16alpha, 28alpha-dihydroxy-13beta, 28-oxydooleanane (9) and 3beta, 28alpha-dihydroxy-16-oxo-13beta, 28-oxydooleanane (10). The known compounds isolated from the same extract included 3beta, 16alpha-dihydroxy-13beta, 28-epoxyoleanane (protoprimulagenin A) (11), 3beta-hydroxy-16-oxo-13beta, 28-epoxyoxyoleanane (aegicerin) (12), 3, 16-dioxo-13beta, 28-epoxyoleanane (embilionone) (13), 3beta, 28-dihydroxy-16-oxo-12-oleanene (schimperinone) (14), taraxerone (15), taraxerol (16) and stigmasterol (17). Structure elucidations were carried out spectroscopically.     

Cytotoxic versus anti-inflammatory effects in HeLa,Jurkat T and human peripheral blood cells caused by guaianolide-type sesquiterpene lactones

Four guaianolide type sesquiterpene lactones (SL), namely the new 1,2-dihydro-3-oxo-costic acid guaianyl ester 3beta-O-(1,2-didehydro-3-oxo-costoyloxy)-4beta,10beta-dihydroxy-guaia-1(2)-en-6beta,12-olide (1) and 3beta-O-(1,2-didehydro-3-oxo-costoyloxy)-4beta,10beta-dihydroxy-guaia-1(2)-en-6alpha,12-olide (2), as well as the known moroccolide A [5alphaH-2beta,4-epoxy-3beta-hydroxy-guaia-1(10),11(13)-dien-6beta,12-olide, 3] and 3beta-O-(2-methylbutyryl)-moroccolide A [5alphaH-2beta,4-epoxy-3beta-(2-methylbutyryloxy)-guaia-1(10),11(13)-dien-6beta,12-olide, 4] were examined for their cytotoxic and anti-inflammatory effects in HeLa, Jurkat T and human peripheral blood mononuclear cells. Compounds 1, 2 and 4 were found to exert a strong cytotoxicity similar in potency in all investigated cell types, whereas 3 was significantly less active. Along with the cytotoxic effect compounds 1 and 4 showed a potent and comparable down-regulation of the mRNAs of the house-keeping genes beta-actin and GAP-DH in PBMCs after 20 h. In contrast, the down-regulation of the PMA-induced mRNA levels of the NF-kappaB-driven pro-inflammatory genes IL-2, IL-6, GM-CSF, TNF-alpha, and IL-1beta in PBMCs is significantly stronger with compound 4. Compound 3 did not significantly modulate cytokine mRNAs levels at biochemically relevant concentrations. The electromobility shift assay (EMSA), revealed a stronger inhibition of NF-kappaB for 1 (IC(50) 2.5 microM) than for 4 (IC(50) 5 microM). Both compounds were also subjected to an IL-6 luciferase reporter gene assay and showed IC(50) values of 1.0 (1) and 1.2 microM (4). Thus, the NF-kappaB inhibition measured by EMSA, as well as the IL-6 luciferase assay did not reflect the differential modulation of pro-inflammatory genes measured with RT-rt-PCR.