Terpenoids and steroids from several euphorbiaceae and pinaceae plants]

During the course of a search for biologically active constituents from unexamined plant sources, several biogenetically interesting new di- and tri-terpenes and steroids were isolated from several weeds and shrubs of Euphorbiaceae and the bark, leaves and cones of several Pinaceae trees which had been treated as wastes in the forestry industry. Euphorbia supina contained 3,4-seco-5 alpha- and 5 beta-adian-4(23)-ene-3,5-diols and related oxides, oxygenated fern-8-en-3 beta-ols named supinenolones A-E and unusually migrated oxyfernanes having (9S)- and (9R)-7(8-->9)abeo-9-D:C-friedo-B':A'-neogammacerane skeletons named spirosupinane and neospirosupinane, while E. chamaesyce contained 3,4-seco-oleana-4(23), 18-dien-3-oic acid, 3,4-seco-8 beta H-ferna-4(23),9(11)-dien-3-oic acid and two oxygenated obtusifoliols. The bark of Phyllanthus flexuosus (Euphorbiaceae) contained 11 beta-hydroxy-D:A-friedo-olean-1-en-3-one, lup-20(29)-ene-3 beta, 15 alpha-diol, olean-12-ene-3 beta,15 alpha-diol and olean-12-ene-3 beta,15 alpha,24-triol together with trichadenic acid B for which we revised the structure to 3 beta-hydroxy-D:A-friedo-oleanan-27-oic acid. Two 26-nor-D:A-friedo-olean-14-enes were isolated from P. watsonii. Regarding Pinaceae trees, an unusually migrated abieslactone [(3R, 7S, 9R, 23R)-7-hydroxy-3-methoxy-8-oxo-7(8-->9)abeo-lanost-24-eno-26,23-lactone], named spiroveitchionolide, was isolated from the bark of Abies species, besides nine abieslactone analogues. Two pairs of unusually migrated serratanes, piceanonols A and B and jezananals A and B having novel skeletal systems of 14(13-->12) abeo- and 16(15-->14) abeo-serratanes named piceanane and jezanane, respectively, were also isolated from the stem bark of Picea species, besides three 14 beta,15 beta-epoxyserratanes and two 13 alpha,14 alpha-epoxyserratanes. The leaves of Larix kaempferi contained two deformed abietanes named karamatsuic acid (9,10-seco-9,10 alpha-epoxyabieta-8,11,13-trien-18-oic acid) and larikaempferic acid [9 alpha,13 alpha-epoxy-8-oxo-9(8-->7)abeo-7 beta-abietan-18-oic acid], as well as the cones to contain 8 alpha,12 alpha-epidioxy-15-hydroxyabiet-13-en-18-oic acid, three diepoxy-abietan-18-oic acids and two new dehydroabietic acid analogues. Several of the above compounds exhibited inhibitory effects against tumor-promoting and DNA topoisomerase II activities.     

Potent antitumor activity of 3,4-seco-8betaH-Ferna-4(23),9(11)-dien-3-oic acid (EC-2) and 3,4-seco-Oleana-4(23),18-dien-3-oic acid (EC-4), evaluated by an in vitro human cancer cell line panel

3,4-seco-8beta H-Ferna-4(23),9(11)-dien-3-oic acid (EC-2) (1) and 3,4-seco-oleana-4(23),18-dien-3-oic acid (EC-4) (2) isolated from the whole herb of Euphorbia chamaesyce L. were evaluated for their anti-tumor activities using a panel including 39 human cancer cell lines (HCC) coupled with a drug sensitivity database. Compounds 1 and 2 showed strong cytotoxicity against the HCC panel, even though alcohols 1A and 2A and methyl esters 1B and 2B were inactive.     

土槿皮的化学成分研究(英文)

对松科Pinaceae植物金钱松Pseudolarix kaempferi Gord的干燥根皮—土槿皮的化学成分进行了研究。应用硅胶,Sephadex LH-20,MCI柱色谱以及高效液相色谱等技术进行分离纯化,利用化合物的理化常数和波谱数据鉴定其结构。分离并鉴定了26个化合物,分别为:土槿丁酸(1),土槿甲酸(2),土槿乙酸(3),土槿丙酸(4),3β-乙酰氧基-齐墩果烷-11,13(18)二烯(5),3β-乙酰氧基-齐墩果烷-9(11),12二烯(6),3β-羟基-齐墩果烷-11,13(18)二烯(7),3β-羟基-齐墩果烷-9(11),12二烯(8),Celangulatin C(9),Celangulatin E(10),17β-通关藤苷元B(11),11α-O-(2-甲基丁酰基)-12β-O-乙酰基通关藤苷元B(12),11α-O-(2-甲基丁酰基)-12β-O-巴豆酰基(顺芷酰基)通关藤苷元B(13),β-谷甾醇酯(14),伞形花内酯(15),5,7-二羟基香豆素(16),花椒毒素(17),异虎耳草素(18),芒柄花黄素(19),毛蕊异黄酮(20),Cnidimol B(21),胸腺嘧啶(22),3-呋喃甲酸(23),2-呋喃甲酸(24),香草酸(25),原儿茶酸(26)。其中化合物5–24为首次从该植物中分离得到;并首次归属化合物1的1H和13CNMR谱数据。     

Four new terpenoids from the roots of Ligularia narynensis

Four new oplopane and guaiane type sesquiterpenoids (1-3), and a monoterpenoid (4) together with three known monoterpenoids (5-7), have been isolated from the roots of Ligularia narynensis. The structures of 1-4 were elucidated as 3beta,4-diacetoxy-8alpha-(2-methylbutyryloxy)-9alpha-(4-methylsenecioyloxy)-11alpha,12-epoxyoplop-10 (14)-ene (1), 3beta,4-diacetoxy-9alpha-(4-acetoxy-4-methylsenecioyloxy)-2beta,8alpha-di (2-methylbutyryloxy)-11alpha,12-epoxyoplop-10 (14)-ene (2), 2alpha-hydroxy-1betaH,7alphaH,10alphaH-guai-4,11 (12)-dien-3-one (3) and 1alpha,2beta,3alpha,6alpha-tetrahydroxy-p-menthane (4) by spectroscopic methods. 1 and 2 were evaluated for their in vitro cytotoxic activity against cultured SMMC-7721 (human hepatoma), L02 (human hepatocyte), and HL-60 (human promyelocytic leukaemia) cell lines.     

Three new steroidal saponins from Fritillaria pallidiflora

Three new steroidal saponins, pallidiflosides A (1), B (2), and C (3), have been isolated from the dry bulbs of Fritillaria pallidiflora Schrenk. Their structures were elucidated as 26-O-β-d-glucopyranosyl-(25R)-furost-5,20(22)-dien-3β,26-diol-3-O-β-d-xylopyranosyl(1?→?4)-[α-l-rhamnopyranosyl(1?→?2)]-β-d-glucopyranoside (1); 26-O-β-d-glucopyranosyl-3β,26-dihydroxyl-20,22-seco-25(R)-furost-5-en-20,22-dione-3-O-α-l-rhamnopyranosyl(1?→?2)-β-d-glucopyranoside (2); and (25R)-spirost-5-ene-3β,17α-diol-3-O-β-d-glucopyranosyl(1?→?4)-β-d-galactopyranoside (3) by spectroscopic techniques and chemical means.     

Eremophilane sesquiterpenes from Cacalia ainsliaeflora

Chemical investigation of Cacalia ainsliaeflora afforded four new eremophilane sesquiterpenes (1 - 3, 5) and a known sesquiterpene (4), which were identified as 3 beta-angeloyloxy-8 alpha-hydroxy-6 beta-methoxyeremophil-7(11),9(10)-dien-8,12-olide (1), 3 beta-angeloyloxy-6 beta,8 alpha-dihydroxyeremophil-7(11),9(10)-dien-8,12-olide (2), 3 beta-angeloyloxy-8 alpha-hydroxy-6 beta-ethoxyeremophil-7(11),9(10)-dien-8,12-olide (3), 3 beta-angeloyloxy-8-oxo-eremphila-6,9-dien-12-oic acid (4), and 3,8-oxo-eremophila-6,9-dien-12-oic acid (5) respectively. These compounds were assayed against Escherichia coli, Staphylococcus aureus and Bacillus subtilis, and compounds 1, 2, 4 and 5 showed weak antibacterial activity. The structures of the compounds were established by 1D and 2D NMR experiments.     

Synthetic oleanane and ursane triterpenoids with modified rings A and C: a series of highly active inhibitors of nitric oxide production in mouse macrophages

We have designed and synthesized 16 new olean- and urs-1-en-3-one triterpenoids with various modified rings C as potential antiinflammatory and cancer chemopreventive agents and evaluated their inhibitory activities against production of nitric oxide induced by interferon-gamma in mouse macrophages. This investigation revealed that 9(11)-en-12-one and 12-en-11-one functionalities in ring C increase the potency by about 2-10 times compared with the original 12-ene. Subsequently, we have designed and synthesized novel olean- and urs-1-en-3-one derivatives with nitrile and carboxyl groups at C-2 in ring A and with 9(11)-en-12-one and 12-en-11-one functionalities in ring C. Among them, we have found that methyl 2-cyano-3, 12-dioxooleana-1,9(11)-dien-28-oate (25), 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) (26), and methyl 2-carboxy-3,12-dioxooleana-1,9(11)-dien-28-oate (29) have extremely high potency (IC(50) = 0.1 nM level). Their potency is similar to that of dexamethasone although they do not act through the glucocorticoid receptor. Overall, the combination of modified rings A and C increases the potency by about 10 000 times compared with the lead compound, 3-oxooleana-1,12-dien-28-oic acid (8) (IC(50) = 1 microM level). The selected oleanane triterpenoid, CDDO (26), was found to be a potent, multifunctional agent in various in vitro assays and to show antiinflammatory activity against thioglycollate-interferon-gamma-induced mouse peritonitis.     

Two new compounds and anti-HIV active constituents from Illicium verum

Two new compounds named illiverin A (1) and tashironin A (8) were isolated from the roots of Illicium verum, together with seven known compounds: 4-allyl-2-(3-methylbut-2-enyl)-1,6-methylenedioxybenzene-3-ol (2), illicinole (3), 3-hydroxy-4,5-methylenedioxyallyl-benzene (4), (-)-illicinone-A (5), 4-allyl-4-(3-methylbut-2-enyl)-1,2-methylenedioxycyclohexa-2,6-dien-5-one (6), 3,4-seco-(24 Z)- cycloart-4(28),24-diene-3,26-dioic acid, 26-methyl ester (7) and tashironin (9). Based on 1D- and 2D-NMR data (COSY, HMQC, HMBC), the structures of the new compounds were deduced to be (E)-1-[(3-methylbut-2-enyl)oxy]-2-methoxy-4-(prop-1-enyl)benzene (1) and 11-O-debenzoyl-11alpha-O-2-methylcyclopent-1-enecarboxyltashironin (8). Compounds 1-9 were screened for anti-HIV activity in vitro whereby compounds 5 and 7 possessed moderate anti-HIV activity with EC50 values of 16.0 and 5.1 microM with SI values of 18.2 and 15.6, respectively.     

Butyrylcholinesterase inhibitory guaianolides fromAmberboa ramosa

Phytochemical investigation of the whole plant of Amberboa ramosa led to the isolation of six sesquiterpene lactones which could be identified as 8alpha-hydroxy-11beta-methyl-1alphaH, 5alphaH, 6betaH, 7alphaH, 11alphaH-guai-10(14), 4(15)-dien-6, 12-olide(1), 3beta, 8alpha-dihydroxy-11alpha-methyl-1alphaH, 5alphaH, 6betaH, 7alphaH, 11betaH-guai-10(14), 4 (15)-dien-6, 12-olide (2), 3beta, 4alpha, 8alpha-trihydroxy-4beta-(hydroxymethyl)-1alphaH, 5alphaH, 6betaH, 7alphaH-guai-10(14), 11(13)-dien-6, 12-olide (3), 3beta, 4alpha, 8alpha-trihydroxy-4beta-(chloromethyl)-1alphaH, 5alphaH, 6betaH, 7alphaH-guai-10(14),11(13)-dien-6, 12-olide(4), 3beta, 4alpha, dihydroxy-4beta-(hydroxymethyl)-1alphaH, 5alphaH, 6betaH, 7alphaH-guai-10(14),11(13)-dien-6, 12-olide(5), 3beta, 4alpha-dihydroxy-4beta-(chloromethyl)-8alpha-(4-hydroxymethacrylate)-1alphaH, 5alphaH, 6betaH, 7alphaH-guai-10(14),11 (13)-dien-6,12-olide (6) by spectroscopic methods. All of them showed inhibitory potential against butyrylcholinesterase.     

Two new sesquiterpene lactones from Sarcandra glabra

Two new sesquiterpene lactones (1) and (2), along with three known sesquiterpenes, atractylenolide beta (3), chloranthalactone E (4), and ( - )-istanbulin A (5), were isolated from the whole plant of Sarcandra glabra. The structures of two new compounds were established as 8beta,9alpha-dihydroxyeudesman-4(15),7(11)-dien-8alpha,12-olide (1) and 8beta,9alpha-dihydroxylindan-4(5),7 (11)-dien-8alpha,12-olide (2) on the basis of spectroscopic analysis. Compound 3 was isolated from this genus for the first time.     

Pycnanthuquinone C: a new terpenoid-quinone from Pycnanthus angolensis

A new compound containing a unique terpenoid-quinone skeleton, pycnanthuquinone C (1) along with the known sargachromenol (2), prunetin (3), biochanin A (4), calopiptin (5), (12 S,13 S)-12,13-dihydroxylabda-8(17),14-dien-18-oic acid (6), (12 R,13 S)-12,13-dihydroxylabda-8(17),14-dien-18-oic acid (7), and sitosterol 3- O-beta- D-glucopyranoside (8), were isolated from the stem bark of Pycnanthus angolensis. Their structures were elucidated by spectroscopic means and comparison with published data. The antifungal activity of compounds 1, 2 and 3 was evaluated. Compound 1 was active against Trichophyton soudanense. Compound 2 was active against Trichophyton mentagrophytes while compound 3 was active against Microsporum audouinii and Trichophyton mentagrophytes.     

Bioactive steroids from the brown alga Sargassum carpophyllum

By activity-guided fractionation, two new sterols, 3beta,28xi-dihydroxy-24-ethylcholesta-5,23Z-dien (1) and 2a-oxa-2-oxo-5alpha-hydroxy-3,4-dinor-24-ethylcholesta-24(28)-ene (2), together with five known steroids, fucosterol (3), 24-ethylcholesta-4,24(28)-dien-3,6-dione (4), 24xi-hydroperoxy-24-vinylcholesterol (5), 24-ketocholesterol (6), 24R,28R- and 24S, 28S-epoxy-24-ethylcholesterol (7), were isolated from the brown alga Sargassum carpophyllum as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. Compounds 1, 3, 4, 5 and 7 also exhibited cytotoxic activity against various cancer cell lines. The IC50 values for 1 and 5 against HL-60 were 7.8 and 8.5 microg/ml, 3 and 4 against P-388 were 0.7 and 0.8 microg/ml, whereas 7 against MCF-7, HCT-8, 1A9, HOS and PC-3 were 4.0, 8.8, 10.0, 10.0 and 7.2 microg/ml, respectively.     

Bioactive terpenes from the roots of Chloranthus henryi

12,15-Epoxy-5alpha H,9beta H-labda-8(17),13-dien-19-oic acid (1) and 14-methoxy-15,16-dinor-5alpha H,9alpha H-labda-13(E),8(17)-dien-12-one (2), two new labdane-type diterpenes, and 1alpha-hydroxy-8,12-epoxyeudesma-4,7,11-triene-6,9-dione (3), one new eudesmane-type sesquiterpene, were isolated from Chloranthus henryi Hemsl, along with two known compounds, 8beta H-eudesma-4(14),7(11)-dien-12,8-olide (4) and 8beta-hydroxyeudesma-4(14),7(11)-dien-12,8-olide (5). Their structures were established by a combination of 1D- and 2D-NMR spectroscopic techniques. The new compounds 2, 3 and the known compound 4 exhibited antitumor activities against Hela and K562 human tumor cell lines.     

Two new steroidal saponins from the rhizomes of Dioscorea panthaica and their cytotoxic activity.

Two new steroidal saponins, dioscoresides C (1) and D (2), along with a new natural product, pregnadienolone 3-O-beta-gracillimatriose (3), and two known compounds, pregnadienolone 3-O-beta-chacotrioside (4) and pseudoprotodioscin (5), were isolated from the rhizomes of Dioscorea panthaica Prain et Burkill. On the basis of extensive NMR studies and chemical evidence, dioscoresides C and D were determined to be 26-O-beta-D-glucopyranosyl-3 beta,26-dihydroxy-23(S)-methoxy-25(R)-furosta-5,20(22)-dien-3-O-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-beta-D-glucopyranoside and 26-O-beta-D-glucopyranosyl-3 beta,26-dihydroxy-20,22-seco-25(R)-furosta-5-en-20,22-dine-3-O-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1--> 4)]-beta-D-glucopyranoside. These compounds showed mild cytotoxicity against the cancer cell lines, A375, L929, and HeLa, in a dose-dependent manner.     

樟叶胡椒中环氧环己烯类化合物的研究

从樟叶胡椒中分离到三个新的环氧环己烯类化合物，樟叶环氧素A，樟叶环氧素B和樟叶环氧素C。另一个已知化合物巴豆环氧素。经光谱鉴定，其结构分别为1S，2S，3R，6S－1－苯甲酰氧亚甲基－2－羟基－3－苯甲酰氧基－1，6－环氧环己－4－烯（1），rel-1S,2R,5S,6R-1苯甲酰氧亚甲基－2－羟基－5－苯甲酰氧基－1，6－环氧环己－3－烯（2）和rel-1S,2R,5S,6R-2-羟基－3－苯甲酰氧亚甲基－5－苯甲酰氧基－1，6－环氧环己－4－烯（3）。化合物（1），（2），（3）为首次从天然资源中分离得到。     

Terpene and phenolic constituents of <Emphasis Type="Italic">Lactuca indica</Emphasis> L.

We isolated seven terpenes and five phenolic constituents from the aerial parts of Lactuca indica L. using column chromatographic separation of its MeOH extract. Their structures were determined by spectroscopic methods to be trans-phytol (1), 3beta-hydroxyglutin-5-ene (2), 5,6-epoxy-3-hydroxy-7-megastigmen-9-one (3), 11beta-13-dihydrolactucin (4), 2-phenylethyl beta-D-glucopyranoside (5), cichorioside B (6), 1-hydroxylinaloyl-6-O-beta-D-glucopyranoside (7), (6S,9S)-roseoside (8), benzyl-beta-D-glucopyranoside (9), 2-(3'-O-beta-D-glucopyranosyl-4'-hydroxyphenyl)-ethanol (10), 3-(beta-D-glucopyranosyloxymethyl)-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-dihydrobenzofuran (11), and (+)-taraxafolin-B (12). Compounds 1-3, 5, and 7-12 were isolated for the first time from this plant source. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using a Sulforhodamin B bioassay.     

Antibacterial diterpenoids from Sagittaria pygmaea

There were five new diterpenoids, 18-beta-D-3',4'-diacetoxyxylopyranosyl-ent-kaur-16-ene (1), 18-beta-L-3',5'-diacetoxyarabinofuranosyl-ent-kaur-16-ene (2), 18-beta-D-3',6'-diacetoxyglucopyranosyl-ent-kaur-16-ene (3), ent-isopimar-8(14),15-dien-19-oic acid (4), and 5alpha-hydroxy-ent-rosa-15-en-18-oic acid (5), isolated from the whole herb of Sagittaria pygmaea. Their structures and relative configurations were established based on spectroscopic studies, chemical methods, and X-ray crystallographic analysis. Compound 2 exhibited significant antibacterial activity against the oral pathogens, Streptococcus mutans ATCC 25 175 and Actinomyces viscosus ATCC 27 044, with MIC values against both pathogens of 15.6 microg/mL. Compound 3 was active against only A. viscosus ATCC 27 044 with an MIC value of 62.5 microg/mL. Compounds 4 and 5 were active against S. mutans ATCC 25 175 and A. viscosus ATCC 27 044, with MIC values against both pathogens of 125.0 microg/mL.     

PTP1B inhibitors from Ardisia japonica

In bioassay-directed isolation from the whole plant of Ardisia japonica, sixteen known compounds: chrysophanol (1), physcion (2), oleanolic acid (3), euscaphic acid (4), tormentic acid (5), quercetin (6), quercitrin (7), myricitrin (8), kaempferol 3-O-alpha-L-rhamnopyranoside (9), cyclamiretin A 3-O-alpha--rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->2)-[beta-D-glucopyranosyl(1-->4)]-alpha-L-arabinopyranoside (10), (7E)-9-hydroxymegastigma-4, 7-dien-3-on-9-O-beta-D-glucopyranoside (11), bergenin (12), norbergenin (13), rutin (14), kaempferol 3,7-O-alpha-L-dirhamnopyranoside (15), (-)-epigallacatechin 3-O-gallate (16) were obtained. Compounds 1-5, 9, 11 and 14-16 have not been reported previously from this plant. Among these isolates, 2, 3, 6 and 12 showed moderate bioactivity against PTP1B in vitro with IC50 values of 121.50, 23.90, 28.12 and 157 microM, respectively.     

Six new sesquiterpenes from Cacalia ainsliaeflora

Five new eremophilane sesquiterpenes, 3beta,6beta-diangeloyloxy-8beta,10beta-dihydroxyeremophilenolide (1); 6beta-acetoxy-3beta-angeloyloxy-8beta,10beta-dihydroxyeremophilenolide (2); 3beta-angeloyloxy-6beta-methoxyeremophil-7(11),9(10)-dien-8alpha,12-olide (3), 3beta-angeloyloxy-8-oxo-eremophil-6(7)-en-12-oic acid (4); 3beta-angeloyloxy-10beta-hydroxy-8-oxo-eremophil-6(7)-en-12-oic acid (5), and a novel nor-eremophilane derivative, 3beta-angeloyloxy-10beta-hydroxy-8-oxo-eremophil-6(7)-en (6), were isolated from the roots of Cacalia ainsliaeflora. Their structures were elucidated by spectroscopic methods, including 2DNMR. Compounds 1 and 2 were assayed against P388 and A549 Carcinoma cell lines. No positive activities were observed.     

New macrocyclic diterpenoids from Euphorbia esula

The structures of two new macrocyclic jatrophane diterpenoid esters from the whole herb of Euphorbia esula, were established as 11,14-epoxy-3beta,5alpha,7beta,8alpha,9alpha,15beta-hexaacetoxy-12-oxo-13alphaH-jatropha-6(17)-ene (1) and 1alpha,3beta-diacetoxy-5alpha,7beta-dibenzoyloxy-9,14-dioxo-11beta,12alpha-epoxy-2alpha,8alpha,15beta-trihydroxy-13betaH-jatropha-6(17)-ene (2) by a combination of 1D- and 2D-NMR techniques as well as UV, IR and mass spectral data. Bioassay evaluation of all isolates against the human tumor cell lines (B16, KB, SMMC and BGC) indicated that ester 2 was cytotoxic to B16 with the IC50 value being 1.81 microg/ml. In addition, the irritant activity assay indicated that both diterpenoids were inactive (ID(24)50 > 100 microg/ear).