Minor furofurano lignans from the Tibetan herb, Lancea tibetica

Four new furofurano lignans, lantibesides B - D ( 1 - 3) and lantibetin ( 4), along with nine known phenolic compounds were isolated from the EtOH extract of the traditional Tibetan medicinal plant, Lancea tibetica. By means of spectroscopic and chemical methods, the structures of the new compounds were elucidated as (1 R,2 S,5 R,6 S)-2-(3,4-methylenedioxyphenyl)-6-[(3-methoxy-4-beta- D-xylopyranosyloxy(1-->6)-beta- D-glucopyranosyloxy)phenyl]-3,7-dioxabicyclo[3.3.0]octane ( 1), (1 R,2 R,5 R,6 S)-2-(3,4-methylenedioxyphenyl)-6-[(3-methoxy-4-beta- D-xylopyranosyloxy(1-->6)-beta- D-glucopyranosyloxy)phenyl]-3,7-dioxabicyclo [3.3.0]octane ( 2), (1 R,2 R,5 R,6 S)-2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4-beta- D-glucopyranosyloxy)phenyl-3,7-dioxabicyclo[3.3.0]octane ( 3), and (1 R,2 R,5 R,6 S)-2-(3,4-dimethoxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3.3.0] octane ( 4). Compounds 2 and 3 showed weak cytotoxicity against the HL-60 cell line with IC (50) values of 61 and 99 microM, respectively.     

Effects of (+)-eudesmin from the stem bark ofMagnolia kobus DC. var.borealis Sarg. on neurite outgrowth in PC12 cells

(+)-Eudesmin [4,8-bis(3,4-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane] was isolated from the stem bark of Magnolia kobus DC. var. borealis Sarg. and found to have neuritogenic activity. 50 microM (+)-eudesmin induced neurite outgrowth and enhanced nerve growth factor (NGF)-mediated neurite outgrowth from PC12 cells. At this concentration, (+)-eudesmin also enhanced NGF-induced neurite-bearing activity and this activity was partially blocked by various protein kinase inhibitors. These included PD98059, a mitogen-activated protein kinase (MAPK) kinase inhibitor. GF109203X, a protein kinase C (PKC) inhibitor and H89, a protein kinase A (PKA) inhibitor. These results suggest that (+)-eudesmin can induce neurite outgrowth from PC12 cells by stimulating up-stream MAPK, PKC and PKA pathways.     

New constituents of Leontopodium alpinum and their in vitro leukotriene biosynthesis inhibitory activity

Phytochemical investigations of the roots of Leontopodium alpinum Cass. resulted in the isolation and structure elucidation of six novel compounds and two known compounds. Novel constituents could be identified as the polyacetylenes 1-acetoxy-3-angeloyloxy-(4 E,6 E)-tetradeca-4,6-diene-8,10,12-triyne and its (6 Z)-isomer, the kaurenic acid derivative methyl ent-7alpha,9alpha-dihydroxy-15beta-[(2 Z)-2-methyl-but-2-enoyloxy]kaur-16-en-19-oate, the bisabolane derivative (1 R*,3 S*,4 R*,6 S*)-9-(acetoxy)-4-hydroxy-1-[(2Z)-2-methylbut-2-enoyloxy]bisabol-10(11)-ene and the lignans [(2 S,3 R,4 R)-4-(3,4-dimethoxybenzyl)-2-(3,4,5-trimethoxyphenyl)-tetrahydrofuran-3-yl]-methyl-(2 Z)-2-methylbut-2-enoate and its 3,4,5-trimethoxybenzyl derivative. Known compounds, reported here for the first time for the genus Leontopodium, were identified as ent-kaur-16-en-19-oic acid and T-cadinol. The obtained compounds were tested together with 15 previously described compounds of L. alpinum in an ex vivo leukotriene biosynthesis inhibition assay. The highest activities were determined for the bisabolane derivates (IC50: 7.7 to 11.4 microM), one lignan (IC50: 10.7 microM) and the ent-kaurenoate (IC50: 10.4 microM).     

Antimicrobial, cytotoxic lignans and terpenoids from the twigs of Pseudolarix kaempferi

Seven new compounds, including four lignans, (+)-(8S,8′S)-9,9′-dibenzoylsecoisolariciresinol (1), (+)-(8S*,8′R*)-4,4′-dimethyloxomatairesinol (2), (+)-(7S*,8R*,8′R*,9′S*)-9′-n-butoxytsugacetal (3), and pseudolarkaemin A (4), a pyronane glycoside, pseudolarkaemin B (5), an ent-beyerene glycoside, pseudolarkaemin C (6), and a triterpene, 25-epi-pseudolarolide Q (7), along with 25 known compounds (8–32) were isolated from the twigs of Pseudolarix kaempferi. Their structures were elucidated mainly by the analysis of their NMR and MS data. Pseudolarolide C acid (24) was isolated for the first time as a natural product. All compounds were evaluated for antimicrobial activity against Candida albicans and Staphylococcus aureus, and cytotoxic activity against K562, HT-29, B16, BGC-823, BEL-7402, SGC-7901, U251, and A549 cancer cell lines were assayed. Results indicated that the new compounds 3, 7, and some known compounds showed antimicrobial and cytotoxic activities.     

A new furofuran lignan with antioxidant and antiseizure activities from the leaves ofPetasites japonicus

A new furofuran lignan (1) was isolated from the n-butanol fraction of the methanolic extract of the leaves of Petasites japonicus (Sieb. et Zucc.) Maxim. (Compositae). The structure of compound 1 was determined to be 2alpha-(4'-hydroxy-3'-methoxyphenyl)-6alpha-(4"-hydroxy-3"-methoxyphenyl)-8alpha-hydroxy-3,7-dioxabicyclo[3.3.0octane 4'-O-(beta-D-glucopyranoside) by spectroscopic methods including 2D-NMR. In further studies, it was found that the compound 1 expressed an antioxidant activity in DPPH radical scavenging assay, and moreover, ameliorated the seizure in kainic acid-treated mice.     

New monoterpenes from Mentha microphylla

Four new monoterpenes, (1 R*,2 S*)-1,2-dihydroxy- p-menth-4(8)-en-3-one ( 1), (4 S*)-4-hydroxy- p-mentha-1,8-dien-3-one ( 2), (4 S*)-4-methoxy- p-mentha-1,8-dien-3-one ( 3), and (3 R*,4 R*,6 S*)-3-acetoxy-6-hydroxy- p-mentha-1,8-diene ( 4) together with four known compounds have been isolated from the aerial parts of Mentha microphylla. The structures were determined using spectroscopic methods particularly high resolution (1)H-, (13)C-NMR as well as 2D (1)H- (1)H COSY, HMQC and HMBC analysis.     

浙贝素的结构测定

从浙江产贝母(Fritillaria thunbergii Miq)地上部分分离出一个新的3,7-二氧杂环[3,3,O)辛酮-6类化合物,经光谱(¹HNMR,¹³CNMR,HRMS,EI-MS)及X-单晶衍射数据的分析,确定其结构为2-(3′,5′-dimethoxy-4′-hydroxyphenyl)-3,7-dioxabicyclo[3,3,O]octan-6-one,定名为浙贝素(zhebeiresinol)。     

Taraxasterane-type triterpene and neolignans from Geum japonicum Thunb. var. chinense F. Bolle

The phytochemical investigation of the ethanolic extract of the whole plants of Geum japonicum Thunb. var. chinense F. Bolle yielded four new compounds: 20 β,28-epoxy-28-hydroxytaraxasteran-3 β-ol (1), (7R,8R)-4-hydroxy-9'-O-(α-L-rhamnopyranosyl)-3,3',5'-trimethoxy-8-O-4'-neolignan (2), (7R,8S)-4-hydroxy-9'-O-(α-L-rhamnopyranosyl)-3,3',5'-trimethoxy-8-O-4'-neolignan (3), and (7S,8S)-5-methoxycupressoside A (4), as well as 40 other known compounds. Structures were elucidated by physical, chemical, and spectroscopic methods, including 1D and 2D NMR, HRESIMS, and CD experiments. The taraxasterane-type triterpene (1) and lignans (2- 6) are reported for the first time from the GEUM genus. Moreover, all compounds were evaluated for anti-inflammatory activities against NO production in RAW264.7 macrophages, and only moderate activities were detected.     

A cytotoxic meroterpenoid benzoquinone from roots of Cordia globosa

(1a S*,1b S*,7a S*,8a S*)-4,5-Dimethoxy-1a,7a-dimethyl-1,1a,1b,2,7, 7a,8,8a-octahydrocyclopropa cyclopenta[1,2-b]naphthalene-3,6-dione (1), a new meroterpenoid benzoquinone, and microphyllaquinone (2), a known naphthoquinone, have been isolated from roots of Cordia globosa. Both structure determinations were performed by conventional spectroscopic methods, including inverse detection NMR techniques, and by comparison with data from the literature for related compounds. Compound 1 displayed considerable cytotoxic activity against several cancer cell lines with IC50 values in the range of 1.2 to 5.0 microg/mL. The cytotoxic activity seemed to be related to DNA synthesis inhibition, as revealed by the reduction of 5-bromo-2'-deoxyuridine incorporation, and apoptosis induction, as indicated by the acridine orange/ethidium bromide assay and morphological changes after 24 h of incubation on leukemic cells.     

Two new 8-O-4'-type lignans from the stem of Schima superba and their cell growth inhibitory activities against human cancer cell lines

Two new lignans (1 and 2) were isolated from the EtOH extracts of the stem of Schima superba, and elucidated as (7R,8S)-1-(3,4-dimethoxyphenyl)-2-O-(2-methoxy-4-omegahydroxypropylphenyl)propane-1,3-diol (1) and threo-1-(4-hydroxy-3-methoxyphenyl)-1-methoxy-2-{4-[1-formyl-(E)-vinyl]-2-methoxyphenoxy}-3-propanol (2) by spectral analysis. Compounds 1 and 2 showed cell growth inhibitory activity against HeLa, CNE, HepG-2, and HEp-2 cell lines. Compound 1 exhibited significant cytotoxicities with IC?? values of less than 4 μg/ml against all the tested cell lines.     

Protective effect of lignans against sepsis from the roots of Saururus chinensis

In the course of isolating preventive agents from sepsis based on the in vivo assay model from the EtOAc extract of the roots of Saururus chinensis, twelve lignans, sarisan (1), erythro-austrobailignan-6 (2), meso-dihydroguaiaretic acid (3), saucerneol B (4), manassantin B (5), manassantin A (6), rel-(8R,8'R)-dimethyl-(7S,7'R)-bis(3,4-methylenedioxyphenyl)tetrahydro-furan (7), (+)-saururinone (8), sauchinone (9), sauchinone B (10), nectandrin B (11) and machilin D (12), were isolated. Compounds 9 and 10, at a dose of 10 mg/kg, increased survival rates to 80% from 20% for the control experiment, and decreased the plasma levels of tumor necrosis factor-alpha (TNF-alpha) and alanine aminotransferase (ALT) activity in mice administered LPS/D-GalN.     

Roles of phosphoinositide-dependent kinase-1 in α1B-adrenoceptor phosphorylation and desensitization

The role of phosphoinositide-dependent protein kinase-1 (PDK-1) activity on α(1B)-adrenoceptor phosphorylation and function was explored using pharmacological inhibitors and expression of a dominant-negative mutant of this enzyme. Noradrenaline-, phorbol myristate acetate-, lysophosphatidic acid- and epidermal growth factor-mediated α(1B)-adrenoceptor phosphorylation were markedly reduced by the two inhibitors used: UCN-01 [(7-hydroxystaurosporine; (3R*,8S*, 9R*, 10R*,12R*)-2,3,9,10,11,12-hexahydro-3-hydroxy-9-methoxy-8-methyl-10-(methylamino)-8,12-epoxy-1H, 8H-2,7b,12a-triazadibenzo[a,g]-cyclonona[cde]triden-1-one)] and OSU-03012 [(2-amino-N-[4-[5-(2-phenanthrenyl)-3-trifluoromethyl)-1H-pyrazol-1-yl]phenyl]-acetamide)]. A similar effect was observed in cells expressing a PDK-1 dominant-negative mutant. Phosphorylated PDK-1 (S241) and protein kinase C α (T497) were associated with cell membranes in the basal state which increased in response to the hormonal stimuli mentioned previously. UCN-01 essentially abolished phospho-PDK-1 membrane-association and markedly attenuated that of protein kinase C α. Consistent with the findings, UCN-01 reduced lysophosphatidic acid- and epidermal growth factor-induced α(1B-)adrenoceptor desensitization. Our data suggest that PDK-1 plays a permissive role in α(1B)-adrenoceptor desensitization and phosphorylation and participates in the formation of signaling complexes, which delicately modulate receptor function and regulation.     

PMMA-stimulus generalization to the optical isomers of MBDB and 3,4-DMA.

Psychoactive phenylisopropylamines can produce one or more of several different stimulus effects in animals. These effects are typified by the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), the central stimulant amphetamine, and by N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA), an agent whose actions are not yet well understood. The optical isomers of two phenylisopropylamines known to lack DOM and amphetamine-stimulus character, that is N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminobutane (MBDB) and 1-(3,4-dimethoxyphenyl)-2-aminopropane (3,4-DMA), were examined in rats trained to discriminate 1.25 mg/kg of PMMA from vehicle. The PMMA stimulus (ED(50)=0.4 mg/kg) generalized to all four agents: S(+)-MBDB (ED(50)=0.8 mg/kg), R(-)-MBDB (ED(50)=2.0 mg/kg), S(+)-3,4-DMA (ED(50)=2.6 mg/kg) and R(-)-3,4-DMA (ED(50)=3.9 mg/kg). The results show that these agents produce stimulus effects similar to those produced by PMMA. Both isomers of MBDB have been previously demonstrated to substitute for N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) in rats trained to discriminate MDMA from vehicle, but MBDB-trained animals failed to recognize DOM or amphetamine. Similar results were obtained with the 3,4-DMA optical isomers in the present investigation using rats trained to discriminate MDMA, DOM or (+)-amphetamine from vehicle; both isomers of 3,4-DMA substituted for an MDMA stimulus, but not for a DOM or amphetamine stimulus. Taken together, the evidence suggests that PMMA, S(+)-MBDB, R(-)-MBDB, S(+)-3,4-DMA, R(-)-3,4-DMA, and S(+)-MDMA can produce common stimulus effects in rats. The present findings also better define the PMMA stimulus and the structural requirements necessary to produce this type of stimulus effect.     

Lepadins D-F: antiplasmodial and antitrypanosomal decahydroquinoline derivatives from the tropical marine tunicate Didemnum sp

From a new tunicate species, belonging to the genus Didemnum, three alkaloids possessing an unusual and extremely rare decahydroquinoline skeleton and showing significant and selective antiplasmodial and antitrypanosomal activity were obtained as follows: (2R*,3S*,4aR*,5R*,8aS*)-decahydro-3-hydroxy-5-(5'-hydroxyoctyl)-2-methylquinoline (lepadin D,1), its quaternary nitrogen derivative (2), (2R*,2"E,3S*,4aR*,5R*,8aS*)-decahydro-3-hydroxy-5-(5'-hydroxyoctyl)-2-methyl-3-quinolinyl ester 2"-octenoic acid (lepadin E, 3), and (2S*,2"E,3S*,4aR*,5R*,8aS*)-decahydro-3-hydroxy-5-(5'-hydroxyoctyl)-2-methyl-3-quinolinyl ester 2"-octenoic acid (lepadin F, 4). These isolates may well serve as lead structures for the development of new antimalarial drugs.     

MK4588, a new antibiotic related to xanthocillin

A new antibiotic, MK4588, structurally related to xanthocillin, was isolated from the culture broth of Leptosphaeria sp. L-179. Antibiotic MK4588 exhibited inhibitory activity against a limited range of Gram-positive and Gram-negative bacteria. The antibiotic was degraded by alkali to a more active product. The structures of MK4588 and the degradation product were determined to be (1R*,6S*,7S*)-7-(Z)-(1-isocyano-2-(4-methoxyphenyl]ethenyl-1-hydro xy-7- isocyanobicyclo[4,2,0]oct-2-en-4-one and (Z)-2,3-diisocyano-1-(4-methoxyphenyl)buta-1,3-diene, respectively, by NMR spectral analyses coupled with X-ray crystallographic analysis of MK4588.     

Sesquiterpenoid and phenolic glucoside gallates from Lagerstroemia balansae

Three new compounds, including a sesquiterpenoid glucoside gallate, 2 Z,4 E,1' R,2' S,4' R,6' S-dihydrophaseic acid 4'-O-(6'-O-galloyl)-β-D-glucopyranoside (1), two new phenolic glucoside gallates, 4-hydroxy-3,5-dimethoxybenzoic acid 4-O-(6'-O-galloyl)-β-D-glucopyranoside (2) and 3,4-dimethoxyphenol 1-O-(6'-O-galloyl)-β-D-glucopyranoside (3), together with eight known compounds (4-11), have been isolated from the stems of Lagerstroemia balansae. Their structures were elucidated on the basis of chemical and spectroscopic evidences.     

Four new benzofurans from seeds of Styrax perkinsiae

Four new benzofurans trans-5-(3-hydroxypropyl)-7-methoxy-2-[2,3-dihydro-3-hydroxymethyl-7-methoxy-2-(3-methoxy-4-hydroxyphenyl)-benzofuran-5-yl]benzofuran (1), (E)-5-(2-formylvinyl)-7-methoxy-2-(3,4-methylenedioxyphenyl)benzofuran (2), 5-(3-butanoyloxypropyl)-7-methoxy-2-(3,4-methylenedioxyphenyl)benzofuran (3), and 5-(3-hydroxypropyl)-7-hydroxy-2-(3,4-methylenedioxyphenyl) benzofuran (4) were isolated from the seeds of Styrax perkinsiae, together with egonol (5), demethoxyegonol (6), egonol acetate (7), demethoxyegonol acetate (8), egonol glucoside (9), egonol gentiobioside (10), egonol gentiotrioside (11), beta-sitosterol (12), and beta-daucosterol (13). Their structures were established by spectroscopic and chemical methods. Compounds 1 and 4 exhibited cytotoxic activity in vitro using two breast cancer cell lines MCF-7 and MDA-MB-231.     

一种西沙掘海绵Dysidea sp.的化学成分研究

目的 对西沙掘海绵Dysidea sp.进行化学成分研究;方法 运用正相硅胶柱色谱、反相ODS柱色谱、凝胶Sephadex LH-20柱色谱以及高效液相色谱(HPLC)等多种分离手段对西沙掘海绵Dysidea sp.化学成分进行分离纯化;并通过理化性质、波谱学数据等结构信息鉴定其化合物的结构。结果发现：从西沙掘海绵Dysidea sp.中分离鉴定了8个化合物,分别为dictyoceratin C（1）、dactyloquinone B（2）、aminoquinone（3）、dictyoceratin A（4）、dactyloquinone D（5）、dactyloquinone E（6）、(1R*,2E,4R*,7E,10S*,11S*,12R*)-10,18-diacetoxydolabella-2,7-dien-6-one（7）和?,?-unsaturated ester（8）,结论 化合物1?6和8均为首次从该属海绵中分离得到。     

New dihydrochalcones and anti-platelet aggregation constituents from the leaves of Muntingia calabura

Two new dihydrochalcones, 2,3-dihydroxy-4,3',4',5'-tetramethoxydihydrochalcone (1) and 4,2',4'-trihydroxy-3'-methoxydihydrochalcone (2), and a new flavanone, (2R,3R)-(-)-3,5-dihydroxy-6,7-dimethoxyflavanone (3), together with nineteen known compounds have been isolated from the leaves of Muntingia calabura. The structures of three new compounds were determined through spectral analyses including extensive 2D-NMR data. Among the isolates, 2,3-dihydroxy-4,3',4',5'-tetramethoxydihydrochalcone, 5,7-dihydroxy-3-methoxyflavone, 5,7-dihydroxy-6-methoxyflavone, 5,4'-dihydroxy-3,7-dimethoxyflavone, (2S)-7,8,3',4',5'-pentamethoxyflavan, (2S)-5'-hydroxy-7,8,3',4'-tetramethoxyflavan, and methyl gallate exhibited significant anti-platelet aggregation activity in vitro.     

卷柏中一个新木脂素苷的分离与鉴定

目的研究卷柏的化学成分。方法利用大孔吸附树脂、Sephadex LH-20、硅胶柱色谱进行分离纯化，根据化合物的理化性质和光谱数据鉴定结构。结果从卷柏中分离得到4个化合物，分别鉴定为(7S,8r)-7,8-二氢-7-(4-羟基-3,5-二甲氧基苯基)-8-羟甲基-［1′-(7′-羟基)乙基-5′-甲氧基］苯骈呋喃-4-O-β-D-葡糖苷(命名为卷柏苷C，化合物I)、D-甘露醇(化合物II)、酪氨酸(化合物III)、莽草酸(化合物IV)。结论化合物I为新化合物，化合物II和III为首次从卷柏属植物中分离得到,IV为首次从卷柏中分离得到。