Anti-AIDS agents. 37. Synthesis and structure-activity relationships of (3'R,4'R)-(+)-cis-khellactone derivatives as novel potent anti-HIV agents.

To explore the structural requirements of (+)-cis-khellactone derivatives as novel anti-HIV agents, 24 monosubstituted 3', 4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives were synthesized asymmetrically. These compounds included 4 isomeric monomethoxy analogues (3-6), 4 isomeric monomethyl analogues (7-10), 4 4-alkyl/aryl-substituted analogues (11-14), and 12 4-methyl-(+)-cis-khellactone derivatives (15-26) with varying 3', 4'-substituents. These (+)-cis-khellactone derivatives were screened against HIV-1 replication in acutely infected H9 lymphocytes. The results demonstrated that the (3'R,4'R)-(+)-cis-khellactone skeleton, two (S)-(-)-camphanoyl groups at the 3'- and 4'-positions, and a methyl group on the coumarin ring, except at the 6-position, were optimal structural moieties for anti-HIV activity. 3-Methyl- (7), 4-methyl- (8), and 5-methyl- (9) 3',4'-di-O-(S)-camphanoyl-(3'R, 4'R)-(+)-cis-khellactone showed EC(50) and therapeutic index values of <5.25 x 10(-5) microM and >2.15 x 10(6), respectively, in H9 lymphocytes, which are much better than those of DCK and AZT in the same assay. Furthermore, 8 and 9 also showed potent inhibitory activity against HIV-1 replication in the CEM-SS cell line, and most monosubstituted DCK analogues were less toxic than DCK in both assays.     

Non-taxane compounds from the bark of Taxus yunnanensis

From the bark of Taxus yunnanensis, 15 non-taxane compounds were isolated. Through spectroscopic methods such as ID and 2D NMR and MS experiments, one of them was determined as a new abietane-type diterpenoid named taxayunnin (1). The other 14 known compounds were identified as taxamairin C (2), taxamairin A (3), 3beta-hydroxy-sandaracopimaric acid (4), (+)-3-hydroxy-isodrimenin (5), rubrosterone (6), ponasterone A (7), ecdysterone (8), 20-hydroxy-echysone-20,22-monoacetonide (9), 7-oxositosterol (10), stigmast-4-en-6beta-ol-3-one (11), 5alpha,6beta-dihydroxy-daucosterol (12), beta-sitosterol (13), daucosterol (14), 1-O-beta-D-glucopyranosyl-(2S, 3R, 4E, 8Z)-2-N-(2'-hydroxypalmitoy])-octadeca-sphinga-4,8-dienine (15), respectively. Compounds 4-6, 9-12 and 15 were isolated from Taxus plants for the first time.     

Non-taxane compounds from the bark of Taxus yunnanensis

From the bark of Taxus yunnanensis , 15 non-taxane compounds were isolated. Through spectroscopic methods such as 1D and 2D NMR and MS experiments, one of them was determined as a new abietane-type diterpenoid named taxayunnin ( 1 ). The other 14 known compounds were identified as taxamairin C ( 2 ), taxamairin A ( 3 ), 3 g -hydroxy-sandaracopimaric acid ( 4 ), (+)-3-hydroxy-isodrimenin ( 5 ), rubrosterone ( 6 ), ponasterone A ( 7 ), ecdysterone ( 8 ), 20-hydroxy-echysone-20,22-monoacetonide ( 9 ), 7-oxositosterol ( 10 ), stigmast-4-en-6 g -ol-3-one ( 11 ), 5 f ,6 g -dihydroxy-daucosterol ( 12 ), g -sitosterol ( 13 ), daucosterol ( 14 ), 1- O - g - d -glucopyranosyl-(2 S , 3 R , 4 E , 8 Z )-2- N -(2'-hydroxypalmitoyl)-octadeca-sphinga-4,8-dienine ( 15 ), respectively. Compounds 4 - 6 , 9 - 12 and 15 were isolated from Taxus plants for the first time.     

New guaiane sesquiterpene lactones from Ixeris dentata

Three new guaiane-type sesquiterpene lactones (1-3), together with nine related sesquiterpenes (4-12), were isolated from the whole extract of Ixeris dentata (Asteraceae). The chemical structures of isolates 1-12 were established by spectroscopic analyses as 3 β,8 β-dihydroxy-guaia-10(14)-en-1 α,4 α,5 α,6 β,7 α,11 βH-12,6 α-olide (1), ixerin N 6'- O-acetate (2), ixerisoside A 6'- O-acetate (3), ixerin N ( 4), ixerisoside A (5), ixerin M (6), tectroside (7), 8-epidesacylcynaropicrin glucoside (8), 8-epiisolipidiol (9), 11 βH-11,13-dihydrointegrifolin (10) 8 β-hydroxy-4 β,15-dihydrozaluzanin C (11), and integrifolin (12). Compounds 1-12 were evaluated for their inhibitory effect on the proliferation of the cultured human tumor cell lines MES-SA, MES-SA/DX5, HCT-15, and HCT15/CL02 in vitro.     

Novel antimicrobial diterpenoids from Turraeanthus africanus

The dichloromethane-methanol (1/1) extract of the stem bark of Turraeanthus africanus (Meliaceae) showed remarkable antimicrobial activity against Cryptococcus neoformans, Staphylococcus aureus and methicillin-resistant S. aureus. Phytochemical investigation of this extract afforded six new diterpenoid derivatives, (+)-16-acetoxy-12,15-epoxylabda-8(17),12,14-triene ( 3), [16( E),12 S,15 R]-16-acetoxy-12,15-epoxy-15-isopropoxy- ent-labda-8(17),13(16)-diene (turraeanin A, 4), [16( E),12 R,15 S]-16-acetoxy-12,15-epoxy-15-isopropoxy- ent-labda-8(17),13(16)-diene (turraeanin B, 5), [16( E),12 S,15 R]-16-acetoxy-12,15-epoxy-15-methoxy- ent-labda-8(17),13(16)-diene (turraeanin C, 6), [16( E),12 R,15 S]-16-acetoxy-12,15-epoxy-15-methoxy- ent-labda-8(17),13(16)-diene (turraeanin D, 7) and (12 S,13 S,15 R)-12,15-epoxy-15-methoxy- ent-labd-8(17)-en-16-al (turraeanin E, 9) together with the known compounds, 15,16-epoxy- ent-labda-8(17),13(16),14-triene ( 1), (+)-pumiloxide ( 2), ent-labda-8(17),12 ( E)-diene-15,16-dial ( 8) and 16-acetoxy-12( R),15-epoxy-15beta-hydroxylabda-8(17),13 (16)-diene ( 10). Compound 10 was obtained as its acetoxy derivative ( 10a) and compound 11 was the product of hydrolysis of 6. Antimicrobial activity of the isolates was assayed and compounds 8, 9, 10a and 11 exhibited significant activities.     

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.     

Cytotoxic sesquiterpene lactones fromSaussurea calcicola

Seven sesquiterpene lactones were isolated by the chromatographic separation of the MeOH extract of the aerial parts of Saussurea calcicola (Compositae). Their structures were determined spectroscopically to be cynaropicrin (1), arguerin B (2), cebellin F (3), 8alpha-hydroxy-11alpha, 13-dihydrozaluzanin C (4), desacylcynaropicrin (5), 3beta-hydroxy-8alpha-epoxymethylacriloiloxy-4(15),10(14),11(13)-trien-guaian-6,12-olide (6), and kandavanolide (7). Compounds 1 and 2 showed significant cytotoxicity against five cultured human tumor cell lines with ED50 values ranging from 0.23-1.72 microg/mL.     

New guaiane, megastigmane and eudesmane-type sesquiterpenoids and anti-inflammatory constituents from Youngia japonica

Eleven sesquiterpenoids have been isolated from the whole plants of Youngia japonica (Asteraceae). Among these sesquiterpenoids, five were identified as new compounds on the basis of spectroscopic methods and chemical analysis. Their structures were 3-oxo-8alpha-(4-hydoxyphenyl)acetoxy-10(14),11(13)-guaiadien-12,6-olide ( 1), 3beta-[3-(4-hydroxyphenyl)acetyl-beta- D-glucopyranosyloxy]-8alpha-hydroxy-4(15),10(14),11(13)-guaiatrien-12,6-olide ( 2), 3beta-[3-(4-hydroxyphenyl)acetyl-beta- D-glucopyranosyloxy]-4(15),10(14),11(13)-guaiatrien-12,6-olide ( 3), 3alpha,5beta,6alpha-trihydroxy-4alpha-(beta- D-glucopyranosyloxy)-7-megastigmen-9-one ( 4), and 3alpha-(beta- D-glucopyranosyloxy)-4(15),11(13)-eudesmadien-12-oic acid ( 5). The three known components 3beta-(beta- D-glucopyranosyloxy)-8alpha-(4-hydroxyphenyl)acetoxy-4(15),10(14),11(13)-guaiatrien-12,6-olide ( 8), 3beta-(beta- D-glucopyranosyloxy)-4(15),10(14),11 (13)-guaiatrien-12,6-olide ( 9), and 3alpha-hydroxy-4alpha-(beta- D-glucopyranosyloxy)-5,7-megastigmadien-9-one ( 11) showed inhibitory activity against the proliferation of T and B lymphocytes of mice in vitro at concentrations of 1 x 10 ( - 7), 1 x 10 ( - 6), and/or 1 x 10 ( - 5) M without obvious cytotoxicity. Compound 9, the major component of the plant extract, exhibited weak anti-inflammatory activity at a dosage of 50 mg/kg ( p. o.) in in vivo anti-inflammatory experiments of mice.     

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.     

Sesquiterpene lactones from Inula hookeri

Four new sesquiterpene lactones, (1 S,5 R,6 S,7 S,8 R,9 R,10 S,11 S)-6-acetoxy-9-hydroxy-4-oxo-pseudoguai-2(3)-en-12,8-olide, (1 S,2 R,5 R,6 S,7 R,8 S,10 R)-6-acetoxy-2-ethoxy-4-oxo-pseudoguai-11(13)-en-12,8-olide, (1 S,2 R,5 R,6 S,7 R,8 S,10 R)-6-acetoxy-2-hydroxy-4-oxo-pseudoguai-11(13)-en-12,8-olide, and 14-acetoxy-1 β,5 α,7 αH-4 β-hydroxy-guai-9(10),11(13)-dien-12,8 α-olide, along with 26 known sesquiterpene lactones, were isolated from the whole plants of Inula hookeri C. B. Clarke. Their structures were established based on spectroscopic methods including HRESIMS, 1D and 2D NMR, and CD techniques. All compounds were evaluated for their cytotoxic activities against HepG2, HeLa, PC-3, and MGC-803 cell lines by CCK-8 assay. Some of the isolates, especiallly pseudoguaianolides and guaianolides, exhibited significant cytotoxicities against these four examined cell lines.     

Identification of isoflavones in the roots of Pueraria lobata

The isoflavones of the roots of Pueraria lobata (Willd.) Ohwi (Puerariae Radix) were investigated by high-performance liquid chromatography (HPLC) coupled to photodiode array (PDA) and to mass spectroscopy (MS) using atmospheric pressure chemical ionization (APCI) or electrospray ionization (ESI) in combination with collision-activated decomposition (CAD) (HPLC-APCI-CAD-MS or ESI-CAD-MS) for identification of glycosides and HPLC-APCI-CAD-MS for identification of aglycones. The major glycosides are derived from daidzein ( 9) and most are 8- C-glycosides. 3'-Hydroxypuerarin-4'- O-deoxyhexoside ( 2B) and 3'-methoxy-6'- O- D-xylosylpuerarin ( 6) were identified as new constituents. MS data were obtained for puerarin-4'- O- D-glucoside ( 1), 3'-hydroxypuerarin ( 2A), puerarin ( 3), 3'-methoxypuerarin ( 4), 6'- O- D-xylosylpuerarin ( 5), daidzin ( 7) and 3'-methoxydaidzin ( 8), which were previously characterized by NMR analysis. Isoflavones identified in Puerariae Radix comprise 3'-methoxydaidzein ( 10), genistein ( 12), daidzein-7- O-methyl ether ( 13A), 3'-methoxydaidzein-7- O-methyl ether or 3'-methoxyformononetin ( 13B) and biochanin A ( 15), while previous characterization of daidzein ( 9) and formononetin ( 14) was substantiated by MS data. The structure of compound 11 could not be established by MS techniques. The estrogenic activity was mainly located in the aglycone fraction.     

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.     

黄连水提液化学成分的分离与鉴定

目的对黄连(Coptis chinensis Franch.)的化学成分进行研究。方法采用不同柱色谱技术进行分离,通过波谱手段确定化合物结构。结果分离鉴定了22个化合物,其中9个生物碱类化合物,分别为小檗碱(berberine,1)、巴马亭(palmatine,2)、黄连碱(coptisine,3)、表小檗碱(epiberber-ine,4)、药根碱(jatrorrhizine,5)、非洲防己碱(columbamine,6)、groenlandicine(7)、木兰花碱(mag-noflorine,8)、8-氧化黄连碱(8-oxocoptisine,9);9个有机酸类化合物,分别为5-阿魏酰奎宁酸(5-O-feruloyl-D-quinic acid,10)、4-阿魏酰奎宁酸(4-O-feruloyl-D-quinic acid,11)、3-甲氧基-4-羟基苯甲酸(3-methoxy-4-hydroxybenzoic acid,12)、阿魏酸(ferulic acid,13)、香草酸-4-O-β-D-葡萄糖苷(va-nillic acid-4-O-β-D-glucopyranoside,14)、3-(3',4'-二羟基苯基)-(2R)-乳酸-4'-O-β-D-吡喃葡萄糖苷(3-(3',4'-dihydroxyphenyl)-(2R)-lactic acid-4'-O-β-D-glucopyranoside,15)、3-(4'-羟基苯基)-(2R)-乳酸(3-(4'-hydroxyphenyl)-(2R)-lactic acid,16)、3-(3',4'-二羟基苯基)-(2R)-乳酸(3-(3',4'-dihydroxyphenyl)-(2R)-lactic acid,17)、3-(3',4'-二羟基苯基)-(2R)-乳酸甲酯(3-(3',4'-di-hydroxyphenyl)-(2R)-lactic acid methyl ester,18);4个木脂素类化合物,分别为异落叶松树脂素-9-O-β-D-吡喃葡萄糖苷(isolarisiresinol-9-O-β-D-glucopyranoside,19)、(+)-松脂醇-4,4'-O-β-D-吡喃葡萄糖苷((+)-pinoresinol-4,4'-O-β-D-diglucopyranoside,20)、7S,8R,8'R-(+)-落叶松脂素-4,4'-O-β-D-吡喃葡萄糖苷(7S,8R,8'R-(+)-larisiresnol-4,4'-O-β-D-diglucopyranoside,21)、7S,8R,8'R-(+)-落叶松脂素-4-O-β-D-吡喃葡萄糖苷(7S,8R,8'R-(+)-larisiresinol-4-O-β-D-glucopyranoside,22)。结论化合物15、16、18-22为首次从黄连植物中分离得到,化合物16、18、19首次从黄连属植物中分离得到。     

Lignanoids from Solanum lyratum

In the present study, we aimed to investigate the chemical constituents from Solanum lyratum.The constituents were separated by column chromatography on silica gel, Sephadex LH-20 and preparative HPLC. Their structures were elucidated by spectroscopic means. A total of 13 compounds were isolated fromS. lyratumand identified as syringin (1), (+)-isolariciresinol (2), (+)-syringaresinol (3), leptolepisol D (4),(–)-secoisolariciresinol (5), (–)-epi-syringaresinol (6),aviculin(7), zhebeiresinol(8), ciwujiatone(9),(–)-(7′S,8S,8′R)-4,4′-dihydroxy-3,3′,5,5′-tetramethoxy-7′,9-epoxylignan-9′-ol-7-one(10),(+)-lariciresinol(11), (+)-pinoresinol (12) and (+)-medioresinol (13). All the compounds were isolated from S. lyratumfor the first time.     

植物内生真菌Talaromyces sp.的次级代谢产物研究

摘要：目的 对1株植物内生真菌Talaromyces sp.的次级代谢产物进行研究。方法 采用稻米培养基培养,通过正反相 硅胶柱层析、Sephadex LH-20凝胶柱层析、半制备反相高效液相色谱等技术对发酵提取物进行分离纯化,运用质谱、核磁 共振、圆二色谱等波谱技术进行结构鉴定,采用MTT测定化合物的细胞毒活性。结果 从该菌株中共分离鉴定11个已知化 合物,其中包括9个聚酮类化合物(1~9)和2个环肽类化合物(10和11),分别为1-deoxyrubralactone(1)、alternariol(2)、alternariol 5-methyl ether(3)、altenuisol(4)、3-hydroxyalternariol 5-O-methyl ether(5)、(2'R,4'R,5'R)-altenuene(6)、(2'S,4'R,5'R)-isoaltenuene(7)、 (2'R,4'R,5'R)-altenuene-5'-acetoxyester(8)、7-hydroxy-3,5-dimethyl-isochromen-1-one(9)、腾毒素(10)和二氢腾毒素(11)。结论 化合 物1、化合物3~11为首次从该属菌株中分离,化合物2和3在100 μmol/L的浓度下对人膀胱癌J82细胞株具有抑制活性,抑制率分 别为56.9%和59.7%。     

Stereoselective synthesis of sugar-modified enyne analogues of adenosine and uridine. Interaction with S-adenosyl-L-homocysteine hydrolase and antiviral and cytotoxic effects

Sonogashira coupling of (E)-6'-iodohomovinyl nucleosides 1 with (trimethylsilyl)acetylene gave the conjugated 8'-(trimethylsilyl)enyne derivatives of the adenosine 2a and uridine 2b with expected E-stereochemistry. Desilylation of 2a,b with tetrabutylammonium fluoride followed by treatment with N-iodosuccinimide/AgNO(3) afforded 8'-iodoenynes 4a,b. Analogous coupling of (Z)-6'-iodohomovinyl nucleosides 7a,b produced (Z)-8'-(trimethylsilyl)enynes 8a,b, which were deprotected with aqueous trifluoroacetic acid to give the Z-enynes 9a,b. Stereoselective coupling of the adenosine 4'-acetylenic 11 and ethyl (Z)-3-bromoacrylate followed by deprotection gave the conjugated enyne system attached in the reverse orientation at C4' 13. Because of their diverse stereochemical attributes, deprotected enyne analogues 5a, 6a, 9a, and 13 derived from adenosine require a different vicinity for binding with S-adenosyl-l-homocysteine (AdoHcy) hydrolase and/or addition of enzyme-bound water across the conjugated enyne system. Enyne 5a and 8'-iodoenyne 6a produced time-dependent and concentration-dependent inhibition of AdoHcy hydrolase (K(i), 0.55 and 118.5 microM, respectively). No reduction in NAD(+) content of the enzyme and no iodide ion released were observed upon incubation of 6a with the enzyme, while incubation of 5a produced 30% reduction in the NAD(+) content of the enzyme. No specific antiviral activity was noted for 5a,b, 6a,b, 9a,b, and 13 against any of the viruses tested; the E-iodoenynes 6a and 6b inhibited HIV-1 virus (IC(50), 1.1 and 1.8 microM; selectivity index, 7 and 3, respectively). The E-enyne 5a showed activity against cytomegalovirus at a concentration (EC(50), 30 microM) that was 3- to 10-fold lower than the cytotoxic concentration.     

构树叶的化学成分

为研究构树叶(Broussonetia papyrifera)的化学成分，用Diaion HP-20，Toyopearl HW-40C，Sephadex LH-20，silica gel等柱色谱方法进行分离，根据其理化性质和波谱数据鉴定化合物结构。分离得到了19个化合物，分别鉴定为芹菜素(1)，芹菜素-7-O-β-D-吡喃葡糖苷(2)，柯伊利素-7-O-β-D-吡喃葡糖苷(3)，芹菜素-7-O-β-D-吡喃葡糖醛酸苷(4)，牡荆素-7-O-β-D-吡喃葡糖苷(5)，木犀草素(6)，5,7,4′-三羟基-6-C-［a-L-鼠李糖(1→2)］-β-D-葡糖黄酮碳苷(7)，5,7,4′-三羟基-8-C-［α-L-鼠李糖(1→2)］-β-D-葡糖黄酮碳苷(8)，异牡荆素(9)，牡荆素(10)，苯甲酸苯甲酯-2,6-二-O-β-D-吡喃葡糖苷(11)，(2R,3R,5R,6S,9R)-3-羟基-5,6-环氧-β-紫罗兰醇-2-O-β-D-葡糖苷(12)，(2R,3R,5R,6S,9R)-3-羟基-5,6-环氧-乙酰-β-紫罗兰醇-2-O-β-D-葡糖苷(13)，ficustriol (14)，(6S,9S)-玫瑰花苷(15)，3β-羟基-5α,6α-环氧-β-紫罗兰酮-2α-O-β-D-葡糖苷(16)，icariside B₁ (17)，sammangaoside A (18)，3-羟基-5α,6α-环氧-β-紫罗兰酮(19)。化合物11、12、13为新化合物，其余化合物为首次从该属植物中分离得到。     

Chemical Study on Alkaloids from Corydalis bulleyana.

Twenty three isoquinoline-type alkaloids were isolated from whole plant of CORYDALIS BULLEYANA Diels. Sixteen of them were identified as known alkaloids, namely, protopine ( 1), (+)consperine ( 2), (+)acetylcorynoline ( 3), dihydrosangunarine ( 4), (+)acetylisocorynoline ( 6), (+/-)stylopine ( 7), (+)corynoline ( 8), (+)corynoloxine ( 9, (+)isocorynoline ( 10), (-)chelanthifoline ( 13), corycavamine ( 14), (+)scoulerine ( 15), (+)isoboldine ( 16), acetylcorydamine ( 18), allocryptopine ( 21) and corydamine ( 23). The remainder were new alkaloids and were referred to as bulleyanine [(6-acetonylacetylisocorynoline)] ( 5), (+)6-acetonylcorynoline ( 11), (+)12-formyloxycorynoline ( 12), (+)6-oxoacetylcorynoline ( 17), (+)12-hydroxycorynoline ( 19), (+)bulleyanaline [(+)6-acetonyl-12-hydroxycorynoline] ( 20) and (+)norjuziphine ( 22), respectively. Their structures have been elucidated by means of spectral and chemical methods.     

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.     

NMDA receptor dependence of mGlu-mediated depression of synaptic transmission in the CA1 region of the rat hippocampus.

1. The depression of synaptic transmission by the specific metabotropic glutamate receptor (mGlu) agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylate ((1S,3R)-ACPD) was investigated in area CA1 of the hippocampus of 4-10 week old rats, by use of grease-gap and intracellular recording techniques. 2. In the presence of 1 mM Mg2+, (1S,3R)-ACPD was a weak synaptic depressant. In contrast, in the absence of added Mg2+, (1S,3R)-ACPD was much more effective in depressing both the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of synaptic transmission. At 100 microM, (1S,3R)-ACPD depressed the slope of the field excitatory postsynaptic potential (e.p.s.p.) by 96 +/- 1% (mean +/- s.e.mean; n = 7) compared with 23 +/- 4% in 1 mM Mg(2+)-containing medium (n = 17). 3. The depressant action of 100 microM (1S,3R)-ACPD in Mg(2+)-free medium was reduced from 96 +/- 1 to 46 +/- 6% (n = 7) by the specific NMDA receptor antagonist (R)-2-amino-5-phosphonopentanoate (AP5; 100 microM). 4. Blocking both components of GABA receptor-mediated synaptic transmission with picrotoxin (50 microM) and CGP 55845A (1 microM) in the presence of 1 mM Mg2+ also enhanced the depressant action of (1S,3R)-ACPD (100 microM) from 29 +/- 5 to 67 +/- 6% (n = 6). 5. The actions of (1S,3R)-ACPD, recorded in Mg(2+)-free medium, were antagonized by the mGlu antagonist (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG). Thus, depressions induced by 30 microM (1S,3R)-ACPD were reversed from 48 +/- 4 to 8 +/- 6% (n = 4) by 1 mM (+)-MCPG. 6. In Mg(2+)-free medium, a group I mGlu agonist, (RS)-3, 5-dihydroxyphenylglycine (DHPG; 100 microM) depressed synaptic responses by 74 +/- 2% (n = 18). In contrast, neither the group II agonists ((2S,1'S,2'S)-2-(2'-carboxycyclopropyl)glycine; L-CCG-1; 10 microM; n = 4) and ((2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine; DCG-IV; 100 nM; n = 3) nor the group III agonist ((S)-2-amino-4-phosphonobutanoic acid; L-AP4; 10 microM; n = 4) had any effect. 7. The depolarizing action of (1S,3R)-ACPD, recorded intracellularly, was similar in the presence and absence of Mg(2+)-AP5 did not affect the (1S,3R)-ACPD-induced depolarization in Mg(2+)-free medium. Thus, 50 microM (1S,3R)-ACPD induced depolarizations of 9 +/- 3 mV (n = 5), 10 +/- 2 mV (n = 4) and 8 +/- 2 mV (n = 5) in the three respective conditions. 8. On resetting the membrane potential in the presence of 50 microM (1S,3R)-ACPD to its initial level, the e.p.s.p. amplitude was enhanced by 8 +/- 3% in 1 mM Mg2+ (n = 5) compared with a depression of 37 +/- 11% in the absence of Mg2+ (n = 4). Addition of AP5 prevented the (1S,3R)-ACPD-induced depression of the e.p.s.p. (depression of 4 +/- 5% (n = 5)). 9. It is concluded that activation by group 1 mGlu agonists results in a depression of excitatory synaptic transmission in an NMDA receptor-dependent manner.