Hydroxylation and glucosidation of ent-16beta-Hydroxybeyeran-19-oic acid by Bacillus megaterium and Aspergillus niger

ent-16beta-Hydroxybeyeran-19-oic acid ( 1) has potential antihypertensive activity. To obtain novel and more-effective compounds, 1 was incubated with Bacillus megaterium ATCC 14 581 and Aspergillus niger CCRC 32 720. The structures of the metabolites were determined by HR-FAB-MS, 1D- and 2D-NMR spectral data, and enzymatic hydrolysis. Bacillus megaterium hydroxylated and glucosidated 1 to yield ent-7alpha,16beta-dihydroxybeyeran-19-oic acid ( 2), ent-16beta-hydroxybeyeran-19-oic acid alpha- D-glucopyranosyl ester ( 3), and ent-7alpha,16beta-dihydroxybeyeran-19-oic acid alpha- D-glucopyranosyl ester ( 4). Aspergillus niger hydroxylated 1 to yield ent-1beta,7alpha,16beta-trihydroxybeyeran-19-oic acid ( 5) and ent-1beta,7alpha-dihydroxy-16-oxobeyeran-19-oic acid ( 6). Metabolites 3 - 5 were characterized as new compounds. In addition, 2, 3, 5, and 6 were tested for antihypertensive effects, and we found that 5 and 6 were more potent than the parent compound 1.     

Chemical constituents of Nouelia insignis Franch

Two new diterpenes and ent-15alpha-hydroxykaur-16-en-19-oic acid 11,12-acetonide (3), together with 23 known compounds were isolated from the dried aerial parts of Nouelia insignis Franch. The structures of new compounds were determined to be ent-14beta,15alpha-dihydroxykaur-16-en-19-oic acid (1), ent-14beta-hydroxy-15-oxokaur-16-en-19-oic acid (2) on the basis of spectral and chemical evidence. The structure of ent-11alpha,16alpha-epoxy-15alpha-hydroxy-16S-kaur-19-oic acid (4) was confirmed by X-ray crystallographic analysis.     

豨莶脂溶性成分的研究

从豨莶(Siegesbeckia orientalis L.)的地上部分,分离出八个化合物,其中I和I根据理化性质和光谱数据确定其结构为ent-17-acetoxy-18-isobutyryloxy-16(α)-kauran-19-oicacid(I)和ent-17-ethoxy-16(α)-kauran-19-oicacid(II),均为新化合物,分别被命为豨莶酯酸(siegesesteric acid,I)和豨莶醚酸(siegesetheric acid,I)。其余化合物分别鉴定为腺梗豨莶萜醇酸(ent-16β,17-dihydroxy-kauran-19-oicacid,II),奇任醇(kirenol,IV,β-谷甾醇葡萄糖甙(β-sitosterolglucoside,V),二十一醇(heneicosanol,VI),花生酸甲酯(methyl arachidate,VII)和β-谷甾醇(β-sitosterol,VII)。除奇任醇和β-谷甾醇外,均为首次从该植物中分得。     

Inhibitory Constituents against Cyclooxygenases fromAralia cordata Thunb

Seven diterpenes, four polyacetylenes, a lipid glycerol, and two sterols were isolated from the methylene chloride fraction of the root of Aralia cordata. Their chemical structures were determined as (-)-pimara-8(14),15-dien-19-oic acid (2), pimaric acid (3), (-)-kaur-16-en-19-oic acid (4), 17-hydroxy-ent-kaur-15-en-19-oic acid (9), 7alpha-hydroxy-(-)-pimara-8(14),15-dien-19-oic acid (10), 16alpha,17-dihydroxy-(-)-kauran-19-oic acid (11), 16-hydroxy-17-isovaleroyloxy-ent-kauran-19-oic acid (12), falcarindiol (5), dehydrofalcarindiol (6), dehydrofalcarindiol-8-acetate (7), falcarindiol-8-acetate (8), alpha-mono palmitin (13), stigmasterol (1), and daucosterol (14) by the spectral evidences. These compounds were tested with COX-1 and COX-2 inhibition assays. This study found that compounds 2, 4, 5, 6, 7, 8, and 10 inhibited COX-1 dependent conversion of the exogenous arachidonic acid to PGE2 in a dose-dependent manner with IC50 values of 134.2 microM, 121.6 microM, 170 microM, 50.4 microM, 11.7 microM, 99.6 microM, and 69.6 microM, respectively. But, most of these compounds weakly inhibited COX-2 dependent PGE2 generation. Among them, only compound 4 showed relatively significant inhibitory activity (IC50: 127.6 microM).     

ent-Kaurenoids from the roots of Cacalia pilgeriana

Two new ent-kaurenoids,19-acetoxyl-ent-3beta,17-dihydroxykaur-15-ene (1), 19-acetoxyl-ent-3beta-hydroxykaur-15-en-17-al (2), together with seven known ent-kaurenoids: ent-kaur-16-en-19-al (3), ent-kaur-16-en-19-oic acid (4), ent-kauran-16beta,17-diol (5), ent-15beta, 16beta-epoxy-17-hydroxykauran-19-oic acid (6),19-acetyl-ent-3beta-hydroxyl-kaur-16-ene (7), ent-3beta,19-dihydroxykaur-16-ene (8), ent-17-hydroxykaur-15-ene (9), were isolated from Cacalia pilgeriana. Their structures were elucidated by spectroscopic methods including 2D NMR spectral analysis.     

番荔枝化学成分研究

从番荔枝(Annona squamosa)中分离得到12个化合物,分别鉴定为liriodenine(AS—1),穆坪马兜铃酰胺(moupinamide,AS-2),-(-)-kauran-16α-01-19-oic acid(AS-3),16β,17-dihydroxy-(-)-kauran-19-oic acid(AS-4),anonaine(AS-5),16α,17-dihydroxy-(-)-kauran-19-oic acid(AS-6),(-)-isokaur-15(16)-en-17,19-dioic acid(AS-7),番荔枝酰胺squamosamide(AS-8),16α-methoxy-(-)kauran-19-oicacid(AS-9),sachanoic acid(AS-10),(-)-kauran-19-al-17-oic acid(AS-11),daucosterol(AS-12)。其中,番荔枝酰胺(AS-8)是新化合物,AS-9是第一次从植物中得到的天然产物。     

向日葵二萜化学成分及其细胞毒活性研究

为了研究向日葵(Helianthus annuus L.)的生物活性成分。本文采用色谱法系统研究向日葵的化学成分，根据波谱学分析鉴定了化合物的结构，用MTT法评价其细胞毒活性。从成熟的向日葵花盘中分离鉴定了11个化合物，分别为：对映贝壳杉-2α,16α-二醇(1)，对映贝壳杉-15α,16α-环氧-17-醛-19-酸(2)，对映贝壳杉-16β-醇(3)，phyllocladan-16β-ol (4)，ent-atisan-16α-ol (5)，15-羟基-对映贝壳杉-16-烯-19酸(6)，对映贝壳-15-当归酰氧基-16-烯-19-酸(7)，对映贝壳杉-16-烯-19酸(8)，对映贝壳杉-17-羟基-15-烯-19酸(9)，对映贝壳杉-16β，17-二羟基-19酸(10)和ciliaric acid (11)。其中化合物1和2为新化合物，部分化合物显示一定的细胞毒活性。     

Bioactive triterpenoids from Symplocos chinensis

A new triterpenoid, 2beta,3beta,19alpha,24-tetrahydroxy-23-norurs-12-en-28-oic acid (4), together with three known triterpenoids 3-oxo-19alpha,23,24-trihydroxyurs-12-en-28-oic acid (1), 2alpha,3beta,19alpha,23-tetrahydroxyurs-12-en-28-oic acid (2), 2alpha,3alpha,19alpha,23-tetrahydroxyurs-12-en-28-oic acid (3), was isolated from the roots of Symplocos chinensis. The new triterpenoid shows significant cytotoxic activity against B16 and BGC-823 cells.     

Simultaneous quantification of eight major constituents in Herba Siegesbeckiae by liquid chromatography coupled with electrospray ionization time-of-flight tandem mass spectrometry

A simple and reliable high-performance liquid chromatography coupled with electrospray ionization time-of-flight tandem mass spectrometry method was developed and validated for the determination of the major diterpenoids and flavonoids in the aerial parts of Herba Siegesbeckiae, including Kirenol, hythiemoside B, ent-16β,17,18-trihydroxy-kauran-19-oic acid, ent-17,18-dihydroxy-kauran-19-oic acid, ent-16β,17-dihydroxy-kauran-19-oic acid, 16α-hydro-ent-kauran-17,19-dioic acid, Rhamnetin, 3',4'-dimethoxy quercetin. The separation of eight compounds was performed on a Waters Symmetry Shield TM RP18 column (250mm×4.6mm i.d., 5μm) with gradient elution using a mobile phase consisting of 0.1% aqueous formic acid and acetonitrile containing 0.1% formic acid in selected ion monitoring mode. All calibration curves showed good linearity (r>0.999) within the test ranges. The precision was evaluated by intra- and inter-day tests, which revealed relative standard deviation (RSD) values less than 3.7%. The recoveries for the quantified compounds were between 97.4 and 101.2% with RSD values below 2.4%. According to the literatures, this study represents the first investigation of the simultaneous analysis of multiple components and the method can be applied to determine the amounts of the major compounds in Herba Siegesbeckiae.     

Constituents of the herb ofIsodon excisus var.coreanus

The studies were carried out to evaluate the constituents in the aerial part ofIsodon excisus var.coreanus (Labiatae). From the aqueous fraction of methanol extract, compound 1 (alpha-[[3-(3, 4-dihydroxyphenyl)-1-oxo-2-propenyl]oxy]-3,4-dihydroxy-benzenepropanoic acid), compound II (9-methyl-dihydroferulic acid-4-O-beta-D-glucopyranosyl (1-->2)-alpha-L- rhamnopyranosyl (1-->4)-beta-D-glucopyranoside), compound III (ent-7alpha, 11alpha, 15beta-trihydroxy-kaur-16-en-1-O-beta-D-glucopyranoside) and compound IV (2alpha, 3beta, 7alpha, 23-tetrahydroxy-olean-12-en-28-oic acid 28-O-beta-D-glucopyranoside) were isolated and identified on the basis of their physicochemical and spectroscopic evidences[IR, FAB(-)MS,(1)H-NMR,(13)C-NMR, HMQC,(1)H-(1)H COSY and HMBC (Heteronuclear Multiple Bond Connectivity)]. Especially, New compounds II and III were named isodonin A and Isodonin B respectively.     

Microbial transformation of the anti-diabetic agent corosolic acid by Cunninghamella echinulata

The pentacyclic triterpenoid corosolic acid was metabolized by Cunninghamella echinulata CGMCC 3.2000 to its C-24 aldehyde group metabolite and five other hydroxylated metabolites: madasiatic acid (2), 2α, 3β, 7β-trihydroxyurs-12-en-28-oic acid (3), 2α, 3β, 15α-trihydroxyurs-12-en-28-oic acid (4), 2α, 3β, 6β, 7β-tetrahydroxyurs-12-en-28-oic acid (5), 2α, 3β, 7β, 15α-tetrahydroxyurs-12-en-28-oic acid (6), and 2α, 3β,7β-trihydroxy-24-al-urs-12-en-28-oic acid (7); compounds 3, 5, and 7 were new compounds. The α-glucosidase inhibitory effects of the metabolites were also evaluated.     

Cytotoxic and DNA topoisomerases I and II inhibitory constituents from the roots of<Emphasis Type="Italic">Aralia cordata</Emphasis>

Bioactivity-guided fractionation, based on the DNA topoisomerase inhibitory activity, lead to the isolation of five compounds (1-5) from the methylene chloride extract of the roots of Aralia cordata Thunb. (Araliaceae). These compounds were identified as ent-pimara-8(14), 15-dien-19-oic acid (1), ent-pimara-8(14), 15-dien-18-oic acid (2), 16alpha-hydrogen-17-isovaleryloxy-ent-kauran-19-oic acid (3), 16alpha-hydroxy-17-isovaleryloxy-ent-kauran-19-oic acid (4) and dehydrofalcarindiol-8-acetate (5) from their spectral data. Compound 3 was isolated for the first time from this plant, and also showed the strongest inhibition of both DNA topoisomerase I and II activities, with 53 and 96% inhibitions, respectively, at a concentration of 20 microM. However, all the compounds exhibited either weak or no cytotoxicities against the human colon carcinoma cell line (HT-29), the human breast carcinoma cell line (MCF-7) and human hepato blastoma cell line (HepG-2).     

Abietane diterpenoids from the cones of Larix kaempferi and their inhibitory effects on Epstein-Barr virus activation

Four known (1-3, 8) and four new abietane diterpenes, 15-hydroxy-8alpha,14alpha,12alpha,13alpha-diepoxyabietan-18-oic acid (4), 7alpha,8alpha,13beta,14beta-diepoxyabietan-18-oic acid (5), 18-nor-abieta-8,11,13-triene-4alpha,7alpha,15-triol (6), and abieta-8,11,13-triene-7alpha,15,18-triol (7) were isolated from the CHCl3 extract of the cones of Larix koempferi. A known compound, 13,14-seco-13,14-dioxoabiet-13-en-18-oic acid (8) was isolated from natural sources for the first time. Their structures were determined by chemical and spectroscopic methods including 1D and 2D NMR techniques. The absolute stereostructure of 5 was determined by X-ray crystallographic analysis. The inhibitory effects of these compounds on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), were examined as a primary screening for antitumor promotors.     

Kaurane-type diterpene glycoside from the stem bark of Acanthopanax trifoliatus

A new diterpene glycoside, acantrifoside D ( 1), as well as three known diterpenes (2 - 4) were isolated from the stem bark of Acanthopanax trifoliatus from Vietnam. Based on 1D and 2D NMR spectroscopic data, their chemical structures were determined to be 16alpha,17-dihydroxy- ent-kauran-19-oic acid 16- O-beta- D-glucopyranoside 19- O-beta- D-glucopyranosyl ester (1), 16alpha H,17-isovalerate- ent-kauran-19-oic acid (2), ent-kaur-16-en-19-oic acid ( 3), and ent-pimara-8(14),15-dien-19-oic acid (4). Compounds 2 - 4 had strong inhibitory effects against COX-1 in an in vitro assay, with IC50 values of 0.21, 0.15 and 0.19 mM, respectively.     

New macrocyclic lathyrane diterpenes, from Euphorbia lagascae, as inhibitors of multidrug resistance of tumour cells

The new macrocyclic lathyrane diterpenes latilagascenes A and B ( 1 and 2), the diacetylated derivative of 2, latilagascene C ( 3), and the known diterpenes ent-16alpha,17-dihydroxyatisan-3-one ( 4) and ent-16alpha,17-dihydroxykauran-3-one ( 5), isolated from the methanol extract of Euphorbia lagascae, were examined for their effects on the reversal of multidrug resistance (MDR) on mouse lymphoma cells. Among the active lathyrane derivatives 1 - 3, compound 2 displayed the highest inhibition of rhodamine 123 efflux of human MDR1 gene transfected mouse lymphoma cells when compared to the untreated cells or the positive control verapamil. The new compounds are the first macrocyclic lathyrane diterpenes showing oxidation at C-16, whose structures were characterized by extensive spectroscopic methods, including 2D NMR experiments ( (1)H- (1)H COSY, HMQC, HMBC and NOESY). The known phenolic compounds vanillic acid ( 6), p-salicylic acid ( 7), isofraxidin ( 8) and cleomiscosin A ( 9) were also isolated from this species.     

Anticomplementary activity of triterpenoids from the whole plant of Aceriphyllum rossii against the classical pathway

To provide a better understanding of the anti-complement activity of triterpenoids, seven unusual pentacyclic triterpenoids bearing a carboxyl group at C-27 were evaluated for their anticomplement activities against the classical pathway of the complement system. The triterpenoids were isolated from the whole plant of Aceriphyllum rossii of the family Saxifragaceae and were determined to be 3alpha,23-isopropylidenedioxyolean-12-en-27-oic acid (1), 3-oxoolean-12-en-27-oic acid (2), 3alpha-hydroxyolean-12-en-27-oic acid (3), beta-peltoboykinolic acid (4), 3alpha,23-diacetoxyolean-12-en-27-oic acid (5), 23-hydroxy-3-oxoolean-12-en-27-oic acid (6) and aceriphyllic acid A ( 7). Among them, compounds 2, 3, and 5 showed significant anticomplement activity on the classical pathway with IC (50) values of 71.4, 98.5, and 180.7 microM, respectively, whereas compounds 1, 4, 6, and 7 were inactive. Our findings suggest that both the ketone at C-3 and the methyl at C-23 in the oleanane triterpenoids with a carboxyl group at C-27 are important for the anticomplement activity against the classical pathway.     

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.     

松塔化学成分的研究

目的研究华山松松塔的化学成分。方法用溶剂法和色谱法分离化合物，波谱法鉴定其结构。结果 分离得到4个二萜类化合物，其结构鉴定为7-oxo-12α,13β-dihydroxyabiet-8(14)-en-18-oic acid (I), 7-oxo-13β-hydroxyabiet-8(14)-en-18-oic acid (II), 8(14)-podocarpen-13-on-18-oic acid (III)和lambertianic acid (IV)。结论I为新化合物，其结构鉴定为7-oxo-12α,13β-dihydroxyabiet-8(14)-en-18-oic acid，化合物II，III为首次从该植物中分离得到。     

Triterpenoids from the Flower of Campsis grandiflora K. Schum. as Human Acyl-CoA: Cholesterol Acyltransferase Inhibitors

The flower of Campsis grandiflora K. Schum. was extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH and H2O. From the EtOAc fraction, seven triterpenoids were isolated through the repeated silica gel, ODS column chromatographies and preparative HPLC. From the result of physico-chemical data including NMR, MS and IR, the chemical structures of the compounds were determined as 3beta-hydroxyolean-12-en-28-oic acid (oleanolic acid, 1), 3beta-hydroxyurs-12-en-28-oic acid (ursolic acid, 2), 3beta-hydroxyurs-12-en-28-al (ursolic aldehyde, 3), 2alpha,3beta-dihydroxyolean-12-en-28-oic acid (maslinic acid, 4), 2alpha,3beta-dihydroxyurs-12-en-28-oic acid (corosolic acid, 5), 3beta,23-dihydroxyurs-12-en-28-oic acid (23-hydroxyursolic acid, 6) and 2alpha,3beta,23-trihydroxyolean-12-en-28-oic acid (arjunolic acid, 7). These teriterpenoids were isolated for the first time from this plant. Also, compounds 4, 5, 6, and 7 revealed relatively high hACAT-1 inhibitory activity with the value of 46.2+/-1.1, 46.7+/-0.9, 41.5+/-1.3 and 60.8+/-1.1% at the concentration of 100 microg/mL, respectively.     

中国红树植物角果木的化学成分

目的研究中国红树植物角果木(Ceriops tagal)的次生代谢成分。方法用多种色谱技术进行分离纯化，根据理化性质和波谱数据进行结构鉴定。结果从中国红树植物角果木石油醚部分分离出9个化合物，并确定了它们的结构分别为：tagalsins A (1)，ent-5α-dolabr-4(18)-ene-15S,16-diol (2)，鲨烯(3)，白桦脂酸(4)，羽扇-20(29)-烯-3-酮-28-羧酸(5)，白桦脂醇(6)，羽扇-20(29)-烯-3-酮-28-醇(7)，β-谷甾醇(8)，阿魏酸二十六醇酯(9)。其中化合物1和2为dolabrane型二萜。结论化合物1为新化合物，2～9系首次从该种中分离得到。