Triterpenoid saponins from the roots of Pulsatilla koreana

Six new saponins, five lupanes (1-5) and one oleanane (6), along with 11 known saponins, were isolated from the roots of Pulsatilla koreana. The structures of the new saponins were found to be 23-hydroxy-3beta-[(O-alpha-L-rhamnopyranosyl-(1-->2)-O-[O-beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid (1), 23-hydroxy-3beta-[(O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid (2), 3beta-[(O-alpha-L-rhamnopyranosyl-(1-->2)-O-[O-beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid (3), 3beta-[(O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid (4), 23-hydroxy-3beta-[(O-beta-D-glucopyranosyl-(1-->4)-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid (5), and hederagenin 3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside (6). Their structures were determined on the basis of 1D and 2D NMR ((13)C NMR, (1)H NMR, (1)H-(1)H COSY, HMQC, and HMBC) methods, FABMS, and hydrolysis. All isolated compounds were evaluated for their cytotoxic activity against A-549 human lung carcinoma cells.     

New steroidal alkaloids from Sarcococca saligna

Five new pregnane-type steroidal alkaloids (1-5) have been isolated from Sarcococca saligna. A combination of UV, IR, MS, and 1D and 2D NMR spectroscopic studies established their structures as salignarine A [(20S)-2beta-hydroxy-4beta-acetoxy-5alpha, 6alpha-epoxy-20-(dimethylamino)-3beta-(tigloylamino)pregnane ] (1), salignarine B [(20S)-2beta-hydroxy-20-(dimethylamino)-3beta-(tigloylamino) -pregn-5- ene] (2), salignarine C [(20S)-2beta-hydroxy-20-(dimethylamino)-3beta-(senecioylamino++ +)-pregn- 5-ene] (3), salignarine D [(20S)-20-(dimethylamino)-3beta-(senecioylamino)-5alpha-preg n-16-ene] (4), and salignarine E [(20S)-20-(dimethylamino)-3beta-(tigloylamino)-pregn-4-ene] (5), respectively.     

Sulfated pregnane glycosides from Periploca graeca

Six new pregnane glycosides, four of them sulfated derivatives, were isolated from small branches of Periploca graeca. The compounds were identified as 16alpha-[(6-O-sulfo-beta-D-glucopyranosyl)oxy]pregn-5-en-20-ol-3beta-yl O-(2-O-acetyl-beta-D-digitalopyranosyl)-(1-->4)-beta-D-cymaropyranoside (1), 16alpha-[(6-O-sulfo-beta-D-glucopyranosyl)oxy]pregn-5-en-20-ol-3beta-yl O-beta-D-oleandropyranosyl-(1-->4)-beta-D-oleandropyranoside (2), 16alpha-[(6-O-sulfo-beta-D-glucopyranosyl)oxy]pregn-5-en-20-ol-3beta-yl O-beta-D-oleandropyranoside (3), 16alpha-[(6-O-sulfo-beta-D-glucopyranosyl)oxy]pregn-5-ene-3beta,20-diol (4), 20-O-[(beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl-(1-->2)-beta-D-digitalopyranosyl)oxy]pregn-5-en-16beta-ol-3beta-yl O-beta-D-digitalopyranosyl-(1-->4)-beta-d-cymaropyranoside (5), and calogenin 3-O-beta-D-digitalopyranoside-20-O-beta-D-canaropyranoside (6). Three pregnane glycosides, previously reported from the genus Periploca, were also isolated. Structures were established on the basis of spectroscopic analyses, including 1D and 2D NMR experiments, HRESIMS, elemental analysis, and chemical degradation.     

Antitubercular activity of triterpenoids from Lippia turbinata

Assay-guided fractionation of the antitubercular MeOH-CH(2)Cl(2) extract obtained from Lippia turbinata led to the isolation of four novel triterpenoids-3beta,25-epoxy-3alpha,21alpha-dihydroxy-22beta-(3-methylbut-2-en-1-oyloxy)olean-12-ene-28-oic acid (1); 3beta,25-epoxy-3alpha,21alpha-dihydroxy-22beta-angeloyloxyolean-12-ene-28-oic acid (2); 3beta,25-epoxy-3alpha,21alpha-dihydroxy-22beta-tigloyloxyolean-12-ene-28-oic acid (3); and 3beta,25-epoxy-3alpha-hydroxy-22beta-(2-methylbutan-1-oyloxy)olean-12-ene-28-oic acid (4)-together with the known triterpenoids lantanilic acid (5), camaric acid (6), lantanolic acid (7), and rehmannic acid (8). The MIC values of 1-8 for growth inhibition of Mycobacterium tuberculosis were determined in the radiorespirometric BACTEC system.     

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).     

Activity-guided isolation of triterpenoid acyl CoA cholesteryl acyl transferase (ACAT) inhibitors from Ilex kudincha.

Activity-guided fractionation of a methanol extract of the leaves of Ilex kudincha led to the isolation of seven acyl CoA cholesteryl acyl transferase (ACAT) inhibitory triterpenes. Four of them were identified by spectroscopic methods as ulmoidol (4), 23-hydroxyursolic acid (5), 27-trans-p-coumaroyloxyursolic acid (6), and 27-cis-p-coumaroyloxyursolic acid (7), and three were new compounds named ilekudinols A-C (1-3). The structures of these new triterpenoids were elucidated as 2alpha, 3beta-dihydroxy-24-nor-urs-4(23),11-dien-28,13beta- olide (1), 2alpha, 3beta-dihydroxy-24-nor-urs-4(23),12-dien-28-oic acid (2), and 3beta, 24,28-trihydroxylupane (3). Compounds 1-7 showed potent inhibitory activity in the ACAT assay.     

New triterpenoid saponins from Maesa japonica

New triterpenoid saponins, maejaposides A, B, C, D, and E, were isolated from the roots of Maesa japonica and were, respectively, defined to be 3-O-[beta-D-xylopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->2)-bet a-D-galactopyranosyl-(1-->3)] [beta-D-galactopyranosyl-(1-->2)]beta-D-glucuronopyranosides of 22alpha-[(Z)-2-hexenoyloxy]-13beta,28-oxido-olean++ +-16alpha, 28alpha-diol (1); 22alpha-[2'-methylbutanoyl]-13beta, 28-oxido-olean-16alpha,28alpha-diol (2a) and 22alpha-angeloyloxy-13beta,28-oxido-olean-16a lpha,28alpha-diol (2b); 21beta,22alpha-diangeloyloxy-13beta,28-oxido- olean-16alpha, 28alpha-diol (3); 21beta-angeloyloxy, 22alpha-(2'-methylbutanoyl)-13beta,28-oxido-olean++ +-16alpha, 28alpha-diol (4), and 21beta-angeloyloxy, 22alpha-[(Z)-2'-hexenoyl]-13beta,28-oxido-olean- 16alpha,28alpha-diol (5). Their structures were established on the basis of extensive NMR (DEPT, COSY, HOHAHA, HETCOR, HMBC, and NOESY) and ESIMS/MS studies, along with chemical degradation.     

Chantriolides A and B,two new withanolide glucosides from the rhizomes of Tacca chantrieri

Two new withanolide glucosides, chantriolides A (1) and B (2), were isolated from the rhizomes of Tacca chantrieri. Their structures were determined on the basis of extensive spectroscopic studies and by acid hydrolysis as (22R)-1alpha,12alpha-diacetoxy-2alpha,3alpha;6alpha,7alpha-diepoxy-27-[(beta-d-glucopyranosyl)oxy]-5alpha-hydroxy-16-oxowith-24-enolide (1) and (22R)-1alpha,12alpha-diacetoxy-2alpha,3alpha;6alpha,7alpha-diepoxy-27-[(beta-d-glucopyranosyl)oxy]-5alpha,16beta-dihydroxywith-24-enolide (2), respectively. It is notable that withanolides, which have been almost exclusively isolated from plants of the family Solanaceae to date, have been found in a species in the family Taccaceae in the present study.     

Acinospesigenin-A, -B,and -C: three new triterpenoids from Phytolacca acinosa

Three new triterpenoids, designated as acinospesigenin-A (1), -B (2), and -C (3), isolated from the berries of Phytolacca acinosa, have been characterized as 3 beta-acetoxy-11 alpha,23-dihydroxytaraxer-14-en-28-oic acid, olean-12-en-23-al-2 beta,3 beta-dihydroxy-30-methoxycarbonyl-28-oic acid and olean-12-en-23-al-2 beta,3 beta,11 alpha-trihydroxy-30-methoxycarbonyl-28-oic acid, respectively. The compounds have shown antiedemic activity (LD(50) 10-15 mg/kg mass) in albino rats.     

Sesquiterpenes and aliphatic diketones from cultures of the basidiomycete Conocybe siliginea

Five new tremulane-type sesquiterpenes, 11,12-dihydroxy-1-tremulen-5-one (1), 11,12-epoxy-12beta-hydroxy-1-tremulen-5-one (2), 5alpha,12-dihydroxy-1-tremulen-11-yl 2(S)-pyroglutamate (3), 2alpha,11-dihydroxy-1(10)-tremulen-5,12-olide (4), and 10beta,11-dihydroxy-5,6- seco-1,6(13)-tremuladien-5,12-olide (5), as well as three new aliphatic diketones, 2,3-dihydroxydodecane-4,7-dione (9 and 10) and 1-hydroxydecane-2,5-dione (11), together with three known sesquiterpene analogues, tremulenediol A (6), conocenol B (7), and conocenolide A (8), were isolated from cultures of the basidiomycete Conocybe siliginea.     

Cytotoxic sesquiterpenoids from Eupatorium chinense

Ten new sesquiterpenoids, namely, eupachinilides A-J (1-10), together with seven known sesquiterpenoids, eupachifolin D (11), budlein B (12), 8 beta-(4'-hydroxytiglyloxy)-2 beta-hydroxy-1 alpha H,5 alpha H,6 beta H,7 alpha H-guai-3,10(14),11(13)-trien-6,12-olide (13), 1,10-hydrobahia (14), 2 alpha-hydroxyeupatolide (15), eupaserrin (16), and mollisorin B (17), were isolated from the whole plant of Eupatorium chinense. Their structures were elucidated mainly by spectral methods, especially 2D NMR techniques. Eupachinilides A (1), E (5), F (6), and I (9) exhibited moderate cytotoxic activities against several tumor cell lines. The structures assigned previously for eupachifolins B (11a), C (13a), and D (11) were revised by spectral analysis and 2D NMR techniques.     

New triterpenoid alkaloid cholinesterase inhibitors from Buxus hyrcana

Three new triterpenoid alkaloids, (+)-N-benzoylbuxahyrcanine [(20S)-3beta-benzoylamino-20-dimethylaminobux-9(11)-ene-10alpha-ol] (1), (+)-N-tigloylbuxahyrcanine [(20S)-20-(dimethylamino)-3beta-(2'-methyl-2'-butenoylamino)bux-9(11)-en-10alpha-ol] (2), and (+)-N-isobutyroylbuxahyrcanine [(20S)-20-(dimethylamino)-3beta-(2'-methylpropanoyl)bux-9(11)-en-10alpha-ol] (3), have been isolated from the leaf extracts of Buxus hyrcana collected in Iran. Their structures were determined using spectroscopic methods. The structures of compounds 1 and 2 were unambiguously confirmed by single-crystal X-ray diffraction techniques. Compounds 1-3 were evaluated for their acetylcholinesterase and butyrylcholinesterase inhibitory activities, and compound 2 was found to be active against both enzymes.     

Ursane- and oleanane-type triterpenes from Ternstroemia gymnanthera callus tissues

An investigation on the constituents of the callus tissues of Ternstroemia gymnanthera has led to the isolation of five phytosterols, 15 known triterpenoids, and four new triterpenoids (1-4). The new compounds were characterized by spectroscopic study as 3-epi-corosolic acid lactone (2 alpha,3 alpha-dihydroxyurs-11-en-13 beta,28-olide) (1), 3-epi-ternstroemic acid (2 alpha,3 alpha-dihydroxyurs-12-en-11-on-28-oic acid) (2), ternstroemic acid (2 alpha,3 beta-dihydroxyurs-12-en-11-on-28-oic acid) (3), and gymnantheraic acid (2 alpha,3 alpha-dihydroxy-11 alpha-methoxyurs-12-en-28-oic acid) (4). The isolated triterpenes were compared with those from actinidiaceous plant callus tissues from a chemotaxonomic point of view.     

Isolation and structures of guaianolides from Carpesium macrocephalum

Two new guaianolides, 4alpha,10alpha-dihydroxy-1beta(H),5beta(H)-guai-11(13)-en-8alpha,12-olide (2) and 4beta,10beta-dihydroxy-5alpha(H)-1,11(13)-guaidien-8alpha,12-olide (3), from Carpesium macrocephalum were isolated, and their structures were elucidated on the basis of spectroscopic studies.     

Defensive chemistry of Senecio miser

Three eremophilanolides, 1alpha-acetoxy-8beta-methoxy-10betaH-eremophil-7(11)-en-8alpha,12-olide (1); 1alpha-angeloyloxy-6beta-hydroxy-8beta-methoxy-10betaH-eremophil-7(11)-en-8alpha,12-olide (2); and 1alpha-angeloyloxy-8betaH,10betaH-eremophil-7(11)-en-8alpha,12-olide (3), and two pyrrolizidine alkaloids, integerrimine (4) and its N-oxide (5), were isolated from bioactive fractions of Senecio miser. The structures of the new compounds 1 and 2 were established by NMR spectroscopic analysis and chemical transformation. The X-ray analysis of compound 1 was also performed. Eremophilanolides 1 and 2 and alkaloids 4 and 5 were found to be strong insect antifeedants, further supporting a proposed defensive role for these classes of compounds.     

Potential antitumor-promoting diterpenoids from the stem bark of Picea glehni

A novel rearranged labdane-type diterpenoid, 19(4-->3)abeo-8alpha, 13(S)-epoxylabda-4(18),14-diene (1), and two new abietane-type diterpenoids, 19-nor-abieta-4(18),8,11,13-tetraen-7-one (2) and 12-hydroxydehydroabietic acid (3) were isolated from the stem bark of Picea glehni, together with seven known diterpenoids-13-epimanoyl oxide (4), dehydroabietic acid (5), (11E)-14, 15-bisnor-8alpha-hydroxy-11-labden-13-one (6), abieta-8,11, 13-trien-7-one (7), 9alpha,13alpha-epidioxyabiet-8(14)-en-18-oic acid (8), 9,10alpha-epoxy-9,10-seco-abieta-8,11,13-trien-18-oic acid (9), and methyl 15-hydroxy-7-oxo-dehydroabietate (10). Compounds 5-8 and 10 showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.     

Triterpenoids from the resin of Styrax tonkinensis and their antiproliferative and differentiation effects in human leukemia HL-60 cells

Four new triterpenoids, 6beta-hydroxy-3-oxo-11alpha,12alpha-epoxyolean-28,13beta-olide (1), 3beta,6beta-dihydroxy-11alpha,12alpha-epoxyolean-28,13beta-olide (2), 3beta,6beta-dihydroxy-11-oxo-olean-12-en-28-oic acid (3), and 3beta-hydroxy-12-oxo-13Halpha-olean-28,19beta-olide (4), and five known triterpenes, 19alpha-hydroxy-3-oxo-olean-12-en-28-oic acid (5), 6beta-hydroxy-3-oxo-olean-12-en-28-oic acid (6), sumaresinolic acid (7), siaresinolic acid (8), and oleanolic acid (9), were isolated from the resin of Styrax tonkinensis. The structures of these triterpenoids were determined by physicochemical and spectroscopic methods. The configuration of compound 4 was confirmed by X-ray crystallographic analysis. All these triterpenoids inhibited HL-60 cell growth with IG(50) values ranging from 8.9 to 99.4 microM. Oleanolic acid (9) was the most effective antiproliferative agent, with an IG(50) value of 8.9 microM. While 3beta,6beta-dihydroxy-11-oxo-olean-12-en-28-oic acid (3) exhibited the least effective growth inhibition among these triterpenoids, it induced HL-60 cells to undergo differentiation as measured by an NBT reduction assay.     

Potent CYP3A4 inhibitory constituents of Piper cubeba

The EtOAc-soluble fraction of the water extract of Piper cubeba, having shown potent inhibitory activity on the metabolism mediated by CYP3A4, was subjected to activity-guided isolation to yield two new lignans, (8R,8'R)-4-hydroxycubebinone (1) and (8R,8'R,9'S)-5-methoxyclusin (2), and two new sesquiterpenes, (5 alpha,8 alpha)-2-oxo-1(10),3,7(11)-guaiatrien-12,8-olide (3) and (1 alpha,2 beta,5 alpha,8 alpha 10 alpha)-1,10-epoxy-2-hydroxy-3,7(11)-guaiadien-12,8-olide (4), along with 16 known compounds (5-20). The structures of the isolated compounds were elucidated on the basis of spectroscopic and chemical analyses. The isolated compounds were tested for their inhibitory activity on the metabolism mediated by CYP3A4 or CYP2D6 using [N-methyl-(14)C]erythromycin or [O-methyl-(14)C]dextromethorphan as a substrate, respectively. The compounds (8R,8'R,9'S)-5-methoxyclusin (2), (-)-clusin (10), (-)-yatein (13), ethoxyclusin (15), and (-)-dihydroclusin (17), having one methylenedioxyphenyl moiety in their structures, showed very potent and selective inhibitory activity against CYP3A4 with IC(50) values (0.44-1.0 microM) identical to that of the positive control, ketoconazole (IC(50), 0.72 microM).     

Absolute structures of new briarane diterpenoids from junceella fragilis

Four new diterpenoids with the briarane skeleton, (-)-4-deacetyljunceellolide D (2), (+)-11alpha, 20alpha-epoxyjunceellolide D (3), (-)-11alpha, 20alpha-epoxy-4-deacetyljunceellolide D (4), and (-)-11alpha, 20alpha-epoxy-4-deacetoxyjunceellolide D (5), (+)-junceellolide A (6) [the antipodal derivative of the known (-)-junceellolide A], along with three known briaranes, (-)-junceellolide D (1), (-)-junceellin (7), and (-)-praelolide (8), were isolated from the Indonesian gorgonian Junceella fragilis. The structures of the new compounds were established on the basis of extensive NMR studies and by comparison with the spectral data from other briarane compounds. The absolute configurations for four of the compounds were determined by the modified Mosher method and by unambiguous chemical interconversions.     

Cytotoxic sesquiterpene lactones from Eupatorium lindleyanum

Ten new guaiane type sesquiterpene lactones, namely, eupalinilides A-J (1-10), as well as nine known compounds, eupachinilide C (11), eupachifolin D (12), eupachinilide E (13), 2alpha-hydroxyeupatolide (14), 3-deacetyleupalinin A (15), heliangine (16), 8beta-tigloyloxy-2,3-seco-6betaH,7alphaH-helianga-4Z,11(13)-diene-3,10beta;6, 12-diolid-2-oic acid (17), 8beta-(4'-hydroxytigloyloxy)-3beta,14-dihydroxy-6betaH,7alphaH-germacra-1(10)Z,4Z,11(13)-trien-6,12-olide (18), and 8beta-tigloyloxy-3beta,14-dihydroxy-6betaH,7alphaH-germacra-1(10)Z,4E,11(13)-trien-6,12-olide (19), were isolated from the whole plant of Eupatorium lindleyanum. Eupalinilides B (2), C (3), E (5), F (6), and I (9) have been tested for cytotoxicity against P-388 and A-549 tumor cell lines. The results showed that eupalinilides B (2) and E (5) demonstrated potent cytotoxicity. The structures of these compounds were determined by spectroscopic methods including 1D and 2D NMR spectra.