Diterpenoids from the roots of Euphorbia fischeriana

From the dried roots of Euphorbia fischeriana, seven new diterpenoids, 3alpha,17-dihydroxy-ent-pimara-8(14),15-diene (1), 7beta,11beta,12beta-trihydroxy-ent-abieta-8(14),13(15)-dien-16,12-olide (2), 17-acetoxyjolkinolide B (3), 13beta-hydroxy-ent-abiet-8(14)-en-7-one (4), 12-deoxyphorbaldehyde-13-acetate (5) 12-deoxyphorbaldehyde-13-hexadecacetate (6), and 12-deoxyphorbol-13-(9Z)-octadecanoate-20-acetate (7), and two known compounds, 12-deoxyphorbol-13-decanoate (8) and prostratin (9), were isolated. The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The structure of compound 1 was confirmed by single-crystal X-ray crystallography. Compounds 3 and 8 exhibited potent cytotoxic activity to Ramos B cells with IC50 values of 0.023 and 0.0051 microg/mL, respectively.     

Spiranoid withanolides from Jaborosa odonelliana

Six new spiranoid withanolides, (20R,22R,23S)-5alpha-chloro-6beta,12beta,17beta,22-tetrahydroxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (2), (20R,22R,23S)-5beta,6beta-epoxy-12beta,17beta,22-trihydroxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (3), (20R,22R,23S)-5beta,6beta-epoxy-4beta,12beta,17beta,22-tetrahydroxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (4), (20R,22R,23S)-5alpha,6beta,12beta,17beta,22-pentahydroxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (5), (20R,22R,23S)-6beta,12beta,17beta,22-tetrahydroxy-5alpha-methoxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (6), and (20R,22R,23S)-6beta,12beta,17beta,22-tetrahydroxy-2alpha,5alpha-epidioxy-1-oxo-12,23-cycloergosta-3,24-dien-26,23-olide (7), were isolated from the leaves of Jaborosa odonelliana. Compounds 2-7 were characterized by a combination of spectroscopic methods (1D and 2D NMR, MS) and molecular modeling.     

The microbiological transformation of two 15beta-hydroxy-ent-kaurene diterpenes by Gibberella fujikuroi

The incubation of 15beta-hydroxy-3-oxo-ent-kaur-16-ene (1) with the fungus Gibberella fujikuroi afforded 11beta-hydroxy-3,15-dioxo-ent-kaurane (6), 11beta,15beta-dihydroxy-3-oxo-ent-kaur-16-ene (8), 7beta,11beta,15beta-trihydroxy-3-oxo-ent-kaur-16-ene (9), 7alpha,11beta-dihydroxy-3,15-dioxo-ent-kaurane (7), and 7alpha,11beta,15beta-trihydroxy-3-oxo-ent-kaur-16-ene (10). The incubation of 15beta-hydroxy-ent-kaur-2,16-diene (3) with the same fungus yielded 7alpha,11beta-dihydroxy-15-oxo-ent-kaur-2-ene (12), 7alpha,11beta,15beta-trihydroxy-ent-kaur-2,16-diene (13), 7beta,15beta-dihydroxy-ent-kaur-2,16-dien-19,6-olide (14), 1beta,7beta,15beta-trihydroxy-ent-kaur-2,16-dien-19-oic acid (15), 7alpha,11beta,16alpha-trihydroxy-15-oxo-ent-kaur-2-ene (17), and 7alpha,15beta,17-trihydroxy-11beta,16beta-epoxy-ent-kaur-2-ene (19). These results indicated that a 3-oxo group in ent-kaur-16-ene derivatives inhibits the oxidation at C-19, typical of the biosynthetic pathway of gibberellins and kaurenolides, while a 2,3-double bond or a 15beta-OH does not. In both substrates a 15beta-alcohol directs hydroxylations at C-11(beta) and C-7(alpha), while in those with a 2,3-double bond the functionalization of C-1(beta) is favored.     

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).     

Eremophilane-type sesquiterpene derivatives from Senecio aegyptius var. discoideus

Investigation of a CH(2)Cl(2) extract of the aerial parts of Senecio aegyptius var. discoideus afforded nine eremophilane compounds, of which six are new (1-6), namely, 1beta-hydroxy-8alphaH-eremophil-7(11),9-dien-8beta,12-olide (1), 1beta,8alpha-dihydroxyeremophil-7(11),9-dien-8beta,12-olide (2), 1beta-hydroxy-8alpha-methoxyeremophil-7(11),9-dien-8beta,12-olide (3), 1-oxo-8alpha-methoxy-10alphaH-eremophil-7(11)-en-8beta,12-lactam (4), 1beta,10beta-epoxy-8alpha-hydroxyeremophil-7(11)-en-8beta,12-olide (5), and 1beta,10beta-epoxy-8alpha-methoxyeremophil-7(11)-en-8beta,12-olide (6). The structures of 1-6 were elucidated by spectroscopic methods and by comparison with literature data. The antibacterial activity of the isolated compounds was tested against Bacillus cereus and a Serratia sp.     

New lanostanoids, elfvingic acids A-H, from the fruit body of Elfvingia applanata

Eight new lanostanoids, 12alpha,15beta-dihydroxy-3,7,11,23-tetraoxolanost-8,(20Z)(22)-dien-26-oic acid (1), 7beta,8beta-epoxy-15beta,20S-dihydroxy-3,12,23-trioxolanost-9(11),16-dien-26-oic acid (2), 7beta,8beta-epoxy-3beta,15beta,20S-trihydroxy-12,23-dioxolanost-9(11),16-dien-26-oic acid (3), 7beta,8beta-epoxy-2alpha,3beta,15beta,20S-tetrahydroxy-12,23-dioxolanost-9(11),16-dien-26-oic acid (4), 7beta,8beta-epoxy-3beta,15beta,20S,28-tetrahydroxy-12,23-dioxolanost-9(11),16-dien-26-oic acid (5), 7beta,8beta-epoxy-3beta,15beta,19,20S-tetrahydroxy-12,23-dioxolanost-9(11),16-dien-26-oic acid (6), 8beta,15beta,20S-trihydroxy-3,7,12,23-tetraoxolanost-9(11),16-dien-26-oic acid (7), 7alpha,8alpha-epoxy-15beta,23xi-dihydroxy-12-oxo-3,4-secolanost-4(28),9(11),(20Z)(22)-trien-3,26-dioic acid (8), and the methyl ester of 8 (8a) were isolated from the fruit bodies of Elfvingia applanata. Their structures were established primarily by NMR experiments, and their biological activity against Kato III and Ehlrich cells was investigated.     

Neuroprotective diterpenes from the fruiting body of Antrodia camphorata

Three new compounds, 19-hydroxylabda-8(17)-en-16,15-olide (1), 3beta,19-dihydroxylabda-8(17),11E-dien-16,15-olide (2), and 13-epi-3beta,19-dihydroxylabda-8(17),11E-dien-16,15-olide (3), together with four known compounds, 19-hydroxylabda-8(17),13-dien-16,15-olide (4), 14-deoxy-11,12-didehydroandrographolide (5), 14-deoxyandrographolide, and pinusolidic acid, were isolated from the fruiting bodies of Antrodia camphorata. The structures of compounds 1-3 were elucidated by the analysis of their spectroscopic data. The in vitro neuroprotective activity of all compounds was evaluated, and compounds 1-5 protected neurons from Abeta damage by 39.2, 35.0, 36.7, 30.6, and 27.0%, respectively, at concentrations between 5 and 20 microM.     

New taxonomically significant sesquiterpenoids from Leontodon autumnalis

The methanolic extract of subaerial parts of Leontodon autumnalis afforded four new and two known sesquiterpenoids of the guaiane type. The known compounds were identified by means of (1)H and (13)C NMR spectroscopy as crepidiaside A (1) and B (2). The structures of the new compounds were determined by extensive 1D and 2D NMR experiments as 15-glucopyranosyloxy-2-oxo-guaia-3,11(13)-dien-1alp ha,5alpha, 6beta,7alpha,10alphaH-12,6-olide (3); 15-glucopyranosyloxy-2-oxo-guai-3-en-1alpha,5alpha+ ++,6beta,7alpha, 10alpha,11betaH-12,6-olide (4); 15-hydroxy-2-oxo-guai-3-en-1alpha, 5alpha,6beta,7alpha,10alpha,11betaH-12,6-+ ++olide (5); and 15-glucopyranosyloxy-2-oxo-guaia-3,11(13)-dien-1bet a,5alpha,6beta, 7alpha,10alphaH-12,6-olide (6), respectively. HPLC-DAD and HPLC-MS analyses of crude extracts of subaerial parts of 25 different taxa of the genus Leontodon revealed that compounds 1 and 2 occur in all investigated members of the section Oporinia (L. autumnalis, L. croceus, L. helveticus, L. montaniformis, L. montanus, L. pyrenaicus, and L. rilaensis) and in L. duboisii from the section Kalbfussia. Compounds 1-6 are detectable neither in other investigated taxa of Kalbfussia (L. cichoraceus, L. muelleri, and L. palisae) nor in any members of the subgenus Leontodon. Compounds 3-5 occur in high amounts only in L. croceus and L. pyrenaicus and in samples of L. autumnalis from northwestern Europe. In other members of the section Oporinia, in L. duboisii as well as in samples of L. autumnalis from the Pyrenees, the Alps, the Carpathians, and southern Central Europe, these substances occur only in trace amounts; in L. montanus and its closest relatives, compounds 3-5 are not detectable at all. Compound 6 is only detectable in samples of L. autumnalis, L. helveticus, L. pyrenaicus, L. rilaensis, and L. duboisii.     

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.     

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.     

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).     

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.     

Euphoportlandols A and B, tetracylic diterpene polyesters from Euphorbia portlandica and their anti-MDR effects in cancer cells

Two new tetracyclic diterpene polyesters, euphoportlandols A (1) and B (2), have been isolated along with 12 known tetracyclic triterpenes from an acetone extract of Euphorbia portlandica. Their structures were established as 5alpha,11alpha,14alpha,17-tetraacetoxy-3beta-benzoyloxy-6beta,15beta-dihydroxy-9-oxoseget-8(12)-ene (1) and 5alpha,11alpha,14alpha,17-tetraacetoxy-3beta-benzoyloxy-6beta,15beta-dihydroxy-9-oxosegetane (2), respectively, by spectroscopic data interpretation. Compounds 1 and 2 were evaluated for their ability to inhibit multidrug resistance in cancer cells. Both compounds were found to be inhibitors of P-glycoprotein 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.     

Sesquiterpenes from Ferula penninervis

The ethyl acetate soluble extract of the dried roots of Ferula penninervis gave 17 new sesquiterpenes [15 of the guaiane-type, ferupennins A-O (1-15), and two of the eudesmane-type, 1alpha-hydroxy-2-oxo-5alpha,7beta,11betaH-eudesm-3-en-6alpha,12-olide (16) and penninervin (17)] and nine known sesquiterpenes. The structures of the new compounds were elucidated on the basis of spectroscopic evidence and X-ray analysis. The absolute configuration of ferupennin A (1) was determined by a modified Mosher method.     

A yew in Israel, new taxane derivatives

Five new taxanes, 5alpha,9alpha,10beta,13alpha-tetraacetoxy-14beta-O-(beta-d-glucopyranosyl)taxa-4(20),11-diene (1), 1beta,2alpha,9alpha,10beta-tetrahydroxy-5alpha-cinnamoyoxytaxa-4(20),11-dien-13-one (2), 2alpha,9alpha,10beta-trihydroxy-5alpha-cinnamoyoxytaxa-4(20),11-dien-13-one (3), 9alpha-acetoxy-2alpha,10beta-dihydroxy-5alpha-cinnamoyoxytaxa-4(20),11-dien-13-one (4), and 2alpha,10beta-diacetoxy-1beta,9alpha-dihydroxy-5alpha-cinnamoyoxy-3,11-cyclotaxa-4(20)-dien-13-one (5), have been identified in a Taxus baccata yew grown in Israel from seeds imported from the United States. We have also characterized 40 previously known taxanes from this plant material. The structures of the new taxanes (1-5) were rigorously established with 1D and 2D NMR data and confirmed by high-resolution FAB-mass spectrometry.     

Jatrophane diterpenoids from Euphorbia mongolica as modulators of the multidrug resistance of L5128 mouse lymphoma cells

The dried aerial parts of Euphorbia mongolica afforded three new acylated polyhydroxy diterpenoids based on the jatrophane framework. The structures were established by means of a combination of 1D and 2D NMR techniques and mass spectrometry as (2S,3S,4R,5R,7S,8R,13S,15R)-5alpha,7beta,8alpha-triacetoxy-3beta-benzoyloxy-15beta-hydroxyjatropha-6(17),11E-diene-9,14-dione (1), (2S,3S,4R,5R,7S,8S,9S13S,15R)-5alpha,7beta,8alpha,9alpha,15beta-pentaacetoxy-3beta-benzoyloxyjatropha-6(17),11E-dien-14-one (2), and (2S,3S,4R,5R,7S,8S,9S13S,15R)-3beta,7beta,8alpha,9alpha,15beta-pentaacetoxy-5alpha-benzoyloxyjatropha-6(17),11E-dien-14-one (3). When the isolates were assayed for multidrug resistance-reversing activity in a rhodamine 123 exclusion test using L5178 mouse lymphoma cells, all compounds demonstrated a concentration-dependent effect in inhibiting the efflux pump activity of these tumor cells in the range 11.2-112 microM.     

C-15-functionalized eudesmanolides from Mikania campanulata

The aerial parts of Mikania campanulata Gardner afforded the nine new eudesmanolides (1S,4S,5S,6S,7S,10R)-1-hydroxy-15-acetoxyeudesm-11(13)-en-6,12-olide (1), (1S,4S,5S,6S,7S,10R)-1,4-dihydroxy-15-acetoxyeudesm-11(13)-en-6,12-olide (2), (1R,4S,5S,6S,7S,10R)-1,4-dihydroxy-15-acetoxyeudesm-11(13)-en-6,12-olide (3), (1R,4S,5S,6S,7S,10R)-1-hydroxy-4,15-diacetoxyeudesm-11(13)-en-6,12-olide (4), (1S,4R,5S,6S,7S,10R)-1,15-diacetoxy-4-hydroxyeudesm-11(13)-en-6,12-olide (5), (1S,5S,6S,7S,10R)-1-hydroxy-15-acetoxyeudesma-4(15),11(13)-dien-6,12-olide (6), (1S,5S,6S,7S,10R)-1,15-dihydroxyeudesma-3,11(13)-dien-6,12-olide (7a), (1S,2R,5S,6S,7S,10R)-1,2,15-trihydroxyeudesma-3,11(13)-dien-6,12-olide (8a), and (1R,6S,7S,10R)-1,15-dihydroxyeudesma-4,11(13)-dien-6,12-olide (9a), among which the last three were characterized as their corresponding peracetates (7b-9b). The structures of 1-6 and 7b-9b were elucidated using 1D and 2D NMR measurements, while that of major constituent 1 was confirmed by single-crystal X-ray diffraction analysis, and its absolute configuration evidenced from vibrational circular dichroism measurements, which were compared to results obtained from density functional theory calculations. The chemistry of the large genus Mikania is briefly analyzed.     

秦岭冷杉茎叶的化学成分研究

目的研究秦岭冷杉Abies chensiensis茎叶的化学成分。方法利用大孔吸附树脂、葡聚糖凝胶、硅胶柱色谱、半制备高效液相色谱等多种色谱方法分离纯化,根据理化性质及波谱数据对化合物进行结构鉴定。结果从秦岭冷杉95%乙醇提取物中分离得到24个化合物,分别鉴定为7,14,24-mariesatrien-26,23-olide-3α,23-diol(1)、(23R)-3α-hydroxy-9,19-cyclo-9β-lanost-24-en-26,23-olide(2)、7-oxocallitrisicacid(3)、23-hydroxy-3-oxomariesia-8(9),14,24-trien-26,23-olide(4)、紫果冷杉三萜E(5)、3-oxo-9β-lanosta-7,24-dien-26,23R-olide(6)、7,14,22Z,24-mariesatetraen-26,23-olide-3-one(7)、(+)-rel-3α-hydroxy-23-oxocycloart-25 (27)-en-26-oic acid(8)、cycloart-25-en-3β,24-diol(9)、紫果冷杉三萜H(10)、3-oxo-24,25,26,27-tetranolanost-8-en-23-oic acid(11)、abiesadine C(12)、13β-epidioxy-8(14)-abieten-18-oic acid(13)、dehydroabietic acid(14)、15-hydroxydehydroabietic acid(15)、methyl 18-methoxydehydroabietate(16)、7β-hydroxy dehydroabietic acid(17)、dehydroabietan-18-ol(18)、centdaroic acid(19)、abietic acid(20)、6,8,11,13-abi-etatrien-18-oic acid(21)、abiesadine B(22)、abiesadine N(23)、12β-hydroxyabietic acid(24)。结论所有化合物均为首次从该植物中分离得到,其中化合物11为属内首次分离得到。     

Three new sesquiterpenes from Croton arboreous

Three new sesquiterpenes, 5alpha,7alpha,10betaH-3-patchoulen-2-one (1), 5alpha,7alpha10betaH-4(14)-patchoulen-2alpha-ol (2), and 9alpha,10beta-dihydroxy-2beta,4beta-peroxy-1alpha,5beta,7alphaH-guaiane (3), were isolated from the aerial parts of Croton arboreous along with 14 known compounds. The structures of these compounds were determined on the bases of their spectroscopic data (IR, UV, OR, 1D and 2D NMR, and MS). The anti-inflammatory activity against ear edema in mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) was evaluated for all the pure compounds and showed that compounds 4-7 are active.