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.     

Taxanes with C-5-amino-side chains from the needles of Taxus canadensis

Five taxanes with an amino-side chain on C-5 were identified for the first time in the needles of the Canadian yew, Taxus canadensis. Their structures were characterized as 2alpha,7beta,9alpha,10beta,13-pentaacetoxy-11beta-hydroxy-5alpha-(3'-N,N-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),12-diene (1), 2alpha,9alpha-dihydroxy-10beta,13alpha-diacetoxy-5alpha-(3'-methylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene (2), 2alpha17-dihydroxy-9alpha,10beta,13alpha-triacetoxy-5alpha-(3'-N,N-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene (3), 2alpha-hydroxy-7beta,9alpha,10beta,13alpha-tetraacetoxy-5alpha-(2'-hydroxy-3'-N,N-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene (4), and 9alpha-hydroxy-2alpha,10beta,13alpha-triacetoxy-5alpha-(3'-N,N-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene (5) on the basis of 1D-, 2D-NMR spectroscopic data and high-resolution fast atom bombardment MS analyses. Metabolite (1) was isolated from the needles of the Canadian yew for the first time but had previously been detected in the stems of the Japanese yew, whereas taxanes (2-5) are only now reported. Metabolite (3) is the first reported nitrogen-containing taxane with a 17-hydroxyl substitution.     

Antimalarial constituents from Nauclea orientalis (L.) L

Bioassay-guided fractionation of the antimalarial-active CHCl3 extract of the dried stem of Nauclea orientalis (L.) L. (Rubiaceae) has resulted in the isolation of two novel tetrahydro-beta-carboline monoterpene alkaloid glucosides, naucleaorine (= (16alpha,17beta)-3,14:15,20-tetradehydro-16-ethenyl-17-(beta-D-glucopyranosyloxy)-19alpha-methoxyoxayohimban-21-one; 1) and epimethoxynaucleaorine (2), as well as the known compounds, strictosidine lactam (= (15beta,16alpha,17beta)-19,20-didehydro-16-ethenyl-17-(beta-D-glucopyranosyloxy)oxayohimban-21-one; 3), 3,4,5-trimethoxyphenol (4), 3alpha-hydroxyurs-12-en-28-oic acid methyl ester (5), 3alpha,23-dihydroxyurs-12-en-28-oic acid (6), 3alpha,19alpha,23-trihydroxyurs-12-en-28-oic acid methyl ester (7), and oleanolic acid (8). Compounds 1, 2, 6, and 8 showed moderate in vitro activities against Plasmodium falciparum. Their structures and configurations were elucidated by spectroscopic methods including 1D- and 2D-NMR analyses.     

Sesqui- and diterpenes from the liverwort Gackstroemia decipiens

Six rosanes, 5 beta,11 beta-dihydroxy-ros-15-ene, 5 beta,12 beta-dihydroxy-ros-15-ene, 11 beta-hydroxy-7-oxo-rosa-5,15-diene, 1 alpha,5 beta,11 beta-trihydroxy-7-oxo-ros-15-ene, 5 beta,20-epoxy-20-hydroxy-ros-15-ene and 5 beta,20-epoxy-20-methoxy-ros-15-ene along with the enantiomer of the already reported 11 beta-hydroxy-rosa-5,15-diene and the known 5 beta-hydroxy-ros-15-ene have been isolated from the liverwort Gackstroemia decipiens. Furthermore, the sesquiterpenes 3-acetoxy-7,11-dihydroxy-farnesa-1,5,9-triene and 1 beta,10 beta-epoxy-nardosin-7,11-diene were identified. Their structures were elucidated by NMR spectroscopy.     

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.     

Triterpenoid glycosides and a triterpene from Ilex brevicuspis

Two saponins and a sapogenin were isolated from the leaves of Ilex brevicuspis. Their structures were established by means of spectroscopic methods as brevicuspisaponin 1 (3-O-alpha-L-arabinopyranosyl-20(S)-19 alpha,24-dihydroxyursolic acid), brevicuspisaponin 2 (3-O-alpha-L-arabinopyranosyl-20(S)-19 alpha,23,24-trihydroxyursolic acid) and 23-methylester of 20(S)-3 beta,19 alpha,24-trihydroxyurs-12-en-23,28-dioic acid.     

Four steroidal alkaloids from the leaves of Buxus sempervirens

Four new steroidal alkaloids, N20-formylbuxaminol E [(20S)-16alpha-hydroxy-20-(formylamino)-3beta-(dimethylamino)-9,10 -seco-buxa-9(11),10(19)-diene] (1), O16-syringylbuxaminol E [(20S)-16alpha-syringoyl-3beta-(dimethylamino)-20-(amino)-9, 10-seco-buxa-9(11),10(19)-diene] (2), N20-acetylbuxamine G [(20S)-20-(acetylamino)-3beta-(methylamino)-9,10-seco-buxa-9(11),1 0(19)-diene] (3) and N20-acetylbuxamine E [(20S)-20-(acetylamino)-3beta-(dimethylamino)-9,10-seco-buxa-9(11) ,10(19)-diene] (4) were isolated from the leaves of Buxus sempervirens. Their structures were determined mainly on the basis of 2D NMR studies.     

New 14-hydroxy-taxane and 2alpha,20-epoxy-11(15-->1)abeotaxane from the needles of Taxus canadensis

Two new taxanes were isolated from the needles of Taxus canadensis. Their structures were established as 10beta,13alpha-diacetoxytaxa-4(20),11-diene-5alpha,9alpha,14beta-triol (1) and 4alpha,13alpha-diacetoxy-2alpha,20-epoxy-11(15-->1)abeotaxa-11,15-diene-5alpha,7beta,9alpha,10beta-tetraol (2) on the basis of a spectroscopic analysis.     

Synthetic approach to analogues of 19-norsteroids with an acyclic side chain

Racemic 14 beta-hydroxy-3-methoxy-8 alpha,9 alpha-1,3,5(10)-estratriene-17-one (I), obtained by total synthesis, was converted into a derivative with alkoxycarbonyl-ethylenic side chain, rac-(20E)-21-methoxycarbonyl-19-nor-8 alpha,9 alpha-pregna- 1,3,5(10),20-tetraene-3,14 beta-diol 3-methyl ether (XII) using two Wittig reactions. Analogous derivatives of 5 alpha-androstane were prepared as synthetic models. In the estrane series the stereochemistry of attachement of the side chain in position 17, biological activity of some compounds, and their chromatographic properties were investigated.     

Novel polyhydroxysterols from the Red Sea marine sponge Lamellodysidea herbacea

Chemical investigation of the dichloromethane extract of the Red Sea marine sponge Lamellodysidea herbacea led to the isolation of four novel polyhydroxysteroids: cholesta-8-en-3beta,5alpha,6alpha,25-tetrol (1), cholesta-8(14)-en-3beta,5alpha,6alpha,25-tetrol (2), cholesta-8,24-dien-3beta,5alpha,6alpha-triol (3), and cholesta-8(14),24-dien-3beta,5alpha,6alpha-triol (4). Their structures were identified through 1D and 2D NMR studies. Relative stereochemistries were established by analysis of chemical shifts, coupling constants, and NOESY correlations. Compounds 3-4 showed antifungal activity against Candida tropicalis, with an inhibition diameter of 13 and 11 mm at 10 microg/disc, respectively.     

Cytotoxic triterpenes from the aerial roots of Ficus microcarpa

Six triterpenes, 3beta-acetoxy-12,19-dioxo-13(18)-oleanene (1), 3beta-acetoxy-19(29)-taraxasten-20alpha-ol (2), 3beta-acetoxy-21alpha,22alpha-epoxytaraxastan-20alpha-ol (3), 3,22-dioxo-20-taraxastene (4), 3beta-acetoxy-11alpha,12alpha-epoxy-16-oxo-14-taraxerene (5), 3beta-acetoxy-25-methoxylanosta-8,23-diene (6) along with nine known triterpenes, 3beta-acetoxy-11alpha,12alpha-epoxy-14-taraxerene (7), 3beta-acetoxy-25-hydroxylanosta-8,23-diene (8), oleanonic acid (9), acetylbetulinic acid (10), betulonic acid (11), acetylursolic acid (12), ursonic acid (13), ursolic acid (14), and 3-oxofriedelan-28-oic acid (15) were isolated from the aerial roots of Ficus microcarpa, and their structures elucidated by spectroscopic methods. The in vitro cytotoxic efficacy of these triterpenes was investigated using three human cancer cell lines, namely, HONE-1 nasopharyngeal carcinoma, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells. Compound 8 and pentacyclic triterpenes 9-15 possessing a carboxylic acid functionality at C-28 showed significant cytotoxic activities against the aforementioned cell lines and gave IC50 values in the range 4.0-9.4 microM.     

Cyclooxygenase-2 enzyme inhibitory triterpenoids from Picrorhiza kurroa seeds

A bioassay guided phytochemical study of the ethyl acetate extract of the seeds of Picrorhiza kurroa afforded a new triterpenoid, 2alpha, 3beta, 19beta, 23-tetrahydroxyolean-12-en-28-O-beta-D-glucoside (1), along with five known triterpenoids, 2alpha, 3beta, 19beta, 23-tetrahydroxyolean-12-en-28-oic acid (2), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-O-beta-d-glucoside (3), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-oic acid (4), 2alpha, 3beta, 19beta, trihydroxyolean-12-en-28-oic acid (5), and 2alpha, 3beta, 6beta, 23-tetrahydroxyolean-12-en-28-oic acid (6). Their structures were established by extensive NMR spectral studies. The acetyl derivatives, compounds 7 and 8, were prepared from compounds 1 and 2, respectively, to aid in their structure elucidation. The inhibition of cyclooxygenase-2 (COX-2) enzyme by compounds 1--6 at 100 microg/mL was 38.3%, 39%, 37%, 49.6%, 25%, and 45.0%, respectively. However, compounds 1--6, at 100 microg/mL, did not inhibit cyclooxygenase-1 (COX-1) enzyme. Compound 1 is a novel triterpenoid and compounds 1--6 are isolated for the first time from the seeds of P. kurroa.     

Kahiricosides II-V, cycloartane glycosides from an Egyptian collection of Astragalus kahiricus

Four cycloartane-type saponins, kahiricosides II-V (1-4), were isolated from the aerial parts of Astragalus kahiricus of Egyptian origin. Their structures were established as 9beta,19-cyclolanost-24E-ene-3beta,6alpha,16beta,27-tetraol-3-O-beta-D-glucopyranoside, 9beta,19-cyclolanost-24E-ene-3beta,6alpha,16beta,27-tetraol-3-O-(2'-O-acetyl)-beta-D-glucopyranoside, 9beta,19-cyclolanost-24E-ene-3beta,6alpha,16beta,27-tetraol-3-O-(6'-O-acetyl)-beta-D-glucopyranoside, and 9beta,19-cyclolanost-24E-ene-3beta,6alpha,16beta,27-tetraol-3-O-beta-D-glucopyranosyl-27-O-beta-D-glucopyranoside based on chemical and spectral evidences. All compounds exhibited very weak cytotoxicity against the A2780 ovarian cancer cell line.     

The biotransformation of 18-hydroxy-9-epi-ent-pimara-7,15-diene by Gibberella fujikuroi

Incubation of 18-hydroxy-9-epi-ent-pimara-7,15-diene with the fungus Gibberella fujikuroi gave the compounds 18-hydroxy-7 alpha,8 alpha-epoxy-9-epi-ent-pimara-15-ene, 18-hydroxy-7-oxo-ent-pimara-15-ene, 6 beta, 18-dihydroxy-7 alpha, 8 alpha-epoxy-9-epi-ent-pimara-15-ene, 9 beta,18-dihydroxy-7 alpha, 8 alpha-epoxy-ent-pimara-15-ene and 6 beta, 14 alpha, 18-trihydroxy-9-epi-ent-pimara-7,15-diene. Oxidation of C-19, which is characteristic of the biosynthesis pathway of the gibberellins is not produced.     

Sesquiterpene polyol esters from Tripterygium wilfordii

The extract (T(II)) of Tripterygium wilfordii Hook f. afforded four sesquiterpene esters: 1beta,2beta,5alpha,8beta,11-pentaacetoxy-4alpha-hydroxy-3alpha(2'-methylbutanoyl)-15-nicotinoyl-7-oxo-dihydroagarofuran; 1beta,5alpha,11-triacetoxy-7beta-benzoyl-4alpha-hydroxy-8beta-nicotinoyl-dihydroagarofuran; 1beta,2beta,5alpha,11-tetraacetoxy-8alpha-benzoyl-4alpha-hydroxy-7beta-nicotinoyl-dihydroagarofuran; 5alpha-benzoyl-4alpha-hydroxy-1beta,8alpha-dinicotinoyl-dihydro- agarofuran as well as one other known sesquiterpene ester. Their structures were established on the basis of spectroscopic studies.     

Further constituents from the bark of Holarrhena pubescens.

Three compounds, pubadysone [11 alpha-hydroxy-18,20-oxido-3-oxo-pregna-1,4,17(20)-triene] (1), puboestrene [3-acetoxy-17-oxo-1,3,5(10)-estratriene] (2) and pubamide [3,18-dioxo-11 alpha-hydroxycona-1,4-diene] (3), have been isolated from the bark of Holarrhena pubescens. Their structures have been established through spectroscopic studies.     

Antifungal highly oxygenated guaianolides and other constituents from Ajania fruticulosa.

Three highly oxygenated guaianolides were isolated from the aerial parts of Ajania fruticulosa along with 17 known phytochemicals including a triterpene (alpha-amyrin), two plant sterols (beta-sitosterol, daucosterol), four flavonoids (axillarin, centaureidin, santin and 5,7,4'-trihydroxy-3,3'-dimethoxyflavone), and ten sesquiterpenes [1alpha-hydroperoxy-4beta,8alpha,10alpha,13-tetrahydroxyguaia-2-en-12,6alpha-olide, 1alpha-hydroperoxy-4alpha,10alpha-dihydroxyguaia-9alpha-angeloyloxyguaia-2,11(13)-dien-12,6alpha-olide, 3beta,4alpha-dihydroxyguaia-11(13),10(14)-dien-12,6alpha-olide, 1alpha,4alpha,10alpha-trihydroxy-9alpha-angeloyloxyguaia-2,11(13)-dien-12,6alpha-olide, 1beta,2beta-epoxy-3beta,4alpha,10alpha-trihydroxy-guaia-11(13)-en-12,6alpha-olide and 2-oxo-8alpha-hydroxyguaia-1(10),3,11(13)-trien-12,6alpha-olide, ketoplenolide B, alantolactone, 9beta-hydroxyeudesma-4,11(13)-dien-12-oic acid and 9beta-acetoxyeudesma-4,11(13)-dien-12-oic acid]. The structures of the three guaianolides were elucidated by a combination of spectroscopic methods (EIMS, HREIMS, COSY, HMQC, HMBC and NOESY) as 1beta,2beta-epoxy-3beta,4alpha,8beta,10alpha-tetrahydroxyguaia-11(13)-en-12,6alpha-olide (1), 1beta,2beta-epoxy-3beta,4alpha,9alpha,10alpha-tetrahydroxyguaia-11(13)-en-12,6alpha-olide (2) and 1beta,2beta-epoxy-10alpha-hydroperoxy-3beta,4alpha,8beta-trihydroxyguaia-11(13)-en-12,6alpha-olide (3), respectively. Antifungal bioassay of all isolates showed that guaianolides 1, 2, 3, and 1beta,2beta-epoxy-3beta,4alpha,10alpha-trihydroxyguaia-11(13)-en-12,6alpha-olide were inhibitory to the growth of Candida albicans with MICs being 20, 20, 20, and 40 microg/ml, respectively.     

ent-Isopimarane-type diterpenoids from the New Zealand liverwort Trichocolea mollissima

Two ent-isopimarane-type diterpenoids were isolated from the New Zealand liverwort Trichocolea mollissima (Hook. f. and Tayl.) Gott., together with a known 1alpha-hydroxy-ent-sandaracopimara-8(14),15-diene. Their absolute structures have been established by modified Mosher's method, X-ray crystallography and by analyses of their CD spectra.     

Labdane and pimarane diterpenes from Croton joufra

From the chloroform extract of the leaves of Croton joufra, the diterpenes 2alpha,3alpha-dihydroxy-labda-8(17),12(13),14(15)-triene and 3beta-hydroxy-19-O-acetyl-pimara-8(9),15-dien-7-one, were isolated. Their structures were established by spectroscopic methods. One of the compounds showed weak lethality in the brine shrimp assay.     

Taxane diterpenoids from Taxus yunnanensis and Taxus cuspidata

Chemical examination of the seeds of the Chinese yew, Taxus runnanensis Cheng et L. K. Fu and the Japanese yew, Taxus cuspidata Sieb et Zucc, resulted in the isolation of four taxane diterpenoids. The structures of these taxoids were established as (12alpha)-2alpha-acetoxy-5alpha,9alpha, 10beta-trihydroxy-3,11-cyclotax-4(20)-en-13-one; 2alpha,7beta,13alpha-triacetoxy-5alpha, 9alpha-dihydroxy-2(3-->20)abeotaxa-4(20),11-dien-10-one; 9alpha,10beta-diacetoxy-5alpha-cinnamoyloxytaxa- 4(20),11-dien-13alpha-ol and the known 2alpha,7beta,9alpha,10beta,13-pentaacetoxytax a-4(20),12-diene-5alpha,11beta-diol on the basis of spectral analysis.