Synthesis of acridinyl-thiazolino derivatives and their evaluation for anti-inflammatory, analgesic and kinase inhibition activities

Variety of N-(4-phenyl-3-(2',3',4'(un)substituted phenyl)thiazol-2(3H)-ylidene)-2,4(un)substituted acridin-9-amine (4a-o) and 1-[(2,4-(un)substituted acridin-9-yl)-3-(4-phenyl-3-(2',3',4'(un)substituted phenyl)thiazol-2(3H)-ylidene)]isothiourea (5a-h) derivatives have been synthesized by condensation of 4-phenyl-3-(2',3',4'(un)substituted phenyl)thiazol-2(3H)-imine (3a-g) with 9-chloro-2,4-(un)substituted acridine (1a-c) and 9-isothiocyanato-2,4-(un)substituted acridine (2a-d), respectively. All these compounds were characterized by correct 1H NMR, FT-IR, MS and elemental analyses. These compounds were screened for anti-inflammatory, analgesic and kinase (CDK1, CDK5 and GSK3) inhibition activities. Some compounds exhibited good anti-inflammatory (25-32%) and potent analgesic (50-75%) activities, at 50 mg/kg p.o. A compound, 4o (R1 = H, R2 = OCH3, R3 = CH3, R4 = CH3, R5 = H) exhibited moderate CDK1 (IC50 = 8.5 microM) inhibition activity.     

类芒齿黄芪地下部分化学成分研究

为了解类芒齿黄芪( Astragalus camptodontoides)主要化学成分,从其地下部分甲醇提取物的乙酸乙酯部位分离出19个单体化合物,通过现代波谱分析及理化性质等手段分别鉴定为异补骨脂黄酮(1),4′-hydroxy-isolonchocarpin (2),5-去氧山豆根黄酮(3),shinflavanone (4),khonklonginols H (5),4′-O-methylpreglabridin (6),3′-hydroxy-4′-O-methylglabridin (7),4′-O-methylglabridin (8),8-prenyl-phaseollinisoflavan (9),xambioona (10),光甘草酚(11),粗毛甘草素H (12),methylnissolin (13),邻苯二甲酸异丁酯(14),邻苯二甲酸丁酯异丁酯(15),β-谷甾醇(16),胡萝卜苷(17),齐墩果酸(18),(2S,3S,4R,9E)-1,3,4-trihydroxy-2-[(2′R)-2′- hydr-oxytetraco-sanoylamino]-9-octadecene (19)。化合物1~19均为首次从该植物中获得,化合物1~7为首次从黄芪属(Astraga-lus)植物中分离得到。     

鹿蹄草化学成分研究

从鹿蹄草(Pyrola callianthaH.Andres)中分离得到11个化合物,经光谱分析确定其结构为(4R)-1-四氢萘酮(1),(4S)-1-四氢萘酮(2),夹竹桃麻素(3),没食子酸(4),3,4-二羟基苯甲酸(5),鹿蹄草素(6),5-羟甲基糠醛(7),金丝桃苷(8),2″-O-没食子酰基金丝桃苷(9),鹿蹄草苷B(10),4-羟基-2,7-二甲基萘基-1-O-β-D-吡喃葡萄糖苷(11)。其中化合物1,2,3,5,6,11为首次从该植物中分离得到,化合物7为首次从该属中分离得到。     

鞭打绣球中的一个新单萜苷

从鞭打绣球(Hemiphragma heterophyllum Wall.)全草中分离到1个新单萜苷和7个已知化合物.通过波谱数据分析,新单萜苷的结构鉴定为(4S)-α-萜烯醇-8-O-β-D-比喃木糖-(1→6)-β-D-比喃葡萄糖苷,已知化合物分别鉴定为globularin(2)、(2S 3S,4R,9E)-1,3,4-trihydroxy-2-[(2'R)-hydroxy-tetracosanoylamino]-9-octadecene(3)、β-香树素(4)、齐墩果酸(5)、肉桂酸(6)、β-谷甾醇(7)和胡萝卜甙(8).除化合物2外,其余化合物均为首次从鞭打绣球中分离得到.     

Two novel C29-5beta-sterols from the stems of Opuntia dillenii

Two novel C29-5beta-sterols, opuntisterol [(24R)-24-ethyl-5beta-cholest-9-ene-6beta,12alpha-diol] (1) and opuntisteroside [(24R)-24-ethyl-6beta-[(beta-d-glucopyranosyl)oxy]-5beta-cholest-9-ene-12alpha-ol] (2), together with nine known compounds, beta-sitosterol (3), taraxerol (4), friedelin (5), methyl linoleate (6), 7-oxositosterol (7), 6beta-hydroxystigmast-4-ene-3-one (8), daucosterol (9), methyl eucomate (10) and eucomic acid (11), were isolated from the stems of Opuntia dillenii collected in Guizhou Province, China. Their structures were elucidated mainly by spectroscopic analysis. The absolute configuration of 1 were deduced from comparative 1H NMR data of the (S)- and (R)-methoxyphenyl acetate derivatives. Compounds 6-8, 10 and 11 were isolated from O. dillenii for the first time.     

泰国红树内生真菌土曲霉xy03菌株中新杂萜类成分

采用硅胶柱层析、SephadexLH-20凝胶柱层析和高效液相色谱(HPLC)等技术,从一株红树马六甲木果楝来源的土曲霉Aspergillus terreusxy03的发酵物中分离得到了7个杂萜类化合物:asptercin A(1)、(1R,4aR,6aR,12aR,12bS)-1,3,4,4a,5,6,6a,12,1...     

Tetrahydropyrrolo[3,2-c]azepin-4-ones as a new class of cytotoxic compounds

Pyrroloazepinones 8a-j and 9a-j were designed by structural modification of lead compound 3. These compounds were tested on five tumor cell lines to determine the role of the azeto ring and the 2-methyl substituent in the cytotoxicity of compound 3. Our results show that compounds 8a-j (R1=CH3) have dramatically reduced cytotoxicity, resulting from the loss of the azeto moiety of lead compound 3. By contrast, azepinones 9a-j (R1=4-nitrophenyl) inhibited the proliferation of almost all cancer cell lines tested even though they lack the azeto ring. Preliminary SAR studies with these compounds revealed the importance of halogens at the para- or meta-position of the 1-phenyl moiety. Additionally, derivatives 9a (R2=H), 9e (R2=4-F), and 9g (R2=4-OMe) were selectively cytotoxic to U-251 cells. However, none of the pyrroloazepinones inhibited the enzymatic activity of CDK1/cyclin B, CDK5/p25, and GSK-3.     

牛心朴子须根的化学成分研究

从采自宁夏的萝摩科鹅绒藤属植物牛心朴子 (CynanchumkomaroviiAl.Iljinski.)须根的乙醇提取物中分离鉴定了十个非C2 1 甾体类化合物 :β D 呋喃果糖基 (2→ 1) α D [6 O 芥子酰基 ] 吡喃葡萄糖甙 (1) ,β D (3 O 芥子酰基 ) 呋喃果糖基 (2→ 1) α D [6 O 芥子酰基 ] 吡喃葡萄糖甙 (2 ) ,[6 O β D 吡喃葡萄糖基 (1→ 6 ) β D 吡喃葡萄糖基 1,2 双氧 (4 羟基 3,5 二甲氧基肉桂酰 ) (3) ,7 脱甲氧基娃儿藤碱 (4) ,9 羟基 芳樟醇 3 O β D 吡喃木糖基 (1→ 6 ) β D 吡喃葡萄糖甙 (5 ) ,(2E ,6R) 2 ,6 二甲基 2 ,7 辛二烯 1,6 二醇 (6 ) ,[(+) 丁香素 ](7) ,4′ O demethylepiyangambin(8) ,4′ 羟基 2′ 甲氧基苯乙酮 (9) ,(2S ,3S ,4R ,12E) N [2′ (R) 羟基二十二碳烷基 ] 1,3,4 三羟基 2 酰胺 二十碳烷基 12 烯 (10 )。除化合物 4和 9外 ,其余化合物均为首次从该植物中分离得到。     

Evidence that forskolin binds to the glucose transporter of human erythrocytes

Binding of [4-3H]cytochalasin B and [12-3H]forskolin to human erythrocyte membranes was measured by a centrifugation method. Glucose-displaceable binding of cytochalasin B was saturable, with KD = 0.11 microM, and maximum binding approximately 550 pmol/mg of protein. Forskolin inhibited the glucose-displaceable binding of cytochalasin B in an apparently competitive manner, with K1 = 3 microM. Glucose-displaceable binding of [12-3H]forskolin was also saturable, with KD = 2.6 microM and maximum binding approximately equal to 400 pmol/mg of protein. The following compounds inhibited binding of [12-3H]forskolin and [4-3H]cytochalasin B equivalently, with relative potencies parallel to their reported affinities for the glucose transport system: cytochalasins A and D, dihydrocytochalasin B, L-rhamnose, L-glucose, D-galactose, D-mannose, D-glucose, 2-deoxy-D-glucose, 3-O-methyl-D-glucose, phloretin, and phlorizin. A water-soluble derivative of forskolin, 7-hemisuccinyl-7-desacetylforskolin, displaced equivalent amounts of [4-3H]cytochalasin B or [12-3H]forskolin. Rabbit erythrocyte membranes, which are deficient in glucose transporter, did not bind either [4-3H]cytochalasin B or [12-3H]forskolin in a glucose-displaceable manner. These results indicate that forskolin, in concentrations routinely employed for stimulation of adenylate cyclase, binds to the glucose transporter. Endogenous ligands with similar specificities could be important modulators of cellular metabolism.     

Four new compounds from the leaves of Acer truncatum

Four new compounds, 3-(4-hydroxy-3,5-dimethoxyphenyl)propyl formate (1), 2,6-dimethoxy-4-[(1S)-3-methoxypropyl]phenol (2), (1R,2R)-4-[(3R)-3-hydroxybutyl]-3,3,5-trimethylcyclohex-4-ene-1,2-diol (3), and (1S,3R,3aR,6S,7S,9aR)-decahydro-1-(hydroxymethyl)-1,7-dimethyl-3a,7-methano-3aH-cyclopentacyclooctene (4) were isolated from the leaves of Acer truncatum, together with twelve known compounds. Their structures were elucidated on the basis of extensive spectroscopic techniques. The absolute configuration of compound 3 was established by the modified Mosher's method. All compounds were evaluated for antibacterial activities.     

黑柄炭角菌的化学成分

从黑柄炭角菌(Xylaria nigripe)子实体中分离得到10个化合物,通过波谱分析等方法分别鉴定为(22E,24R)-麦角甾-5,7,22-三烯-3β-醇(1)、5α,8α-过氧-(22E,24R)-麦角甾-6,22-二烯-3β-醇(2)、脑苷酯B(3)、脑苷酯D(4)、stearic acid(5)、甘油的亚油酸三酯(trilinolein,6)、α-kojibiose(7)、D-阿洛糖醇(8)、L-氨基丙酸(9)和尿囊素(10)。所有化合物均为首次从该子实体中分离得到。     

三种毒菌的化学成分研究

本文对三种毒菌的化学成分进行了研究。从光盖伞(Psilocybe spp)分离鉴定了4个化合物,经波谱分析鉴定为:(22E,24R)-麦角甾-7,22-二烯-3β-十八烷酸酯(1)、β-胡萝卜苷(2)、(22E,24R)-5α,6α-环氧麦角甾-8,22-二烯-3β,7α-二醇(3)、色氨酸(4);从假褐云斑鹅膏(Amanita pseudoporphyria)分离鉴定了4个化合物:(22E,24R)-3β-羟基-5α,8α-过氧化麦角甾-6,22-二烯(5)、(22E,24R)-麦角甾-7,22-二烯-3β,5α,6β-三醇(6)、1-O-β-D-吡喃葡萄糖基-(2S,3R,4E,8E,2′R)-2-N-(2′-羟基棕榈酰)-9-甲基-4,8-脱氢鞘氨醇(7)、1-O-β-D-吡喃葡萄糖基-(2S,3R,4E,8E,2′R)-2-N-(2′-羟基十八烷酰)-9-甲基-4,8-脱氢鞘氨醇(8);大青褶伞(Chlorophyllum molybdites)发酵菌丝体分离鉴定了4个化合物:5、6、(22E,24R)-5α,6α-环氧麦角甾-8(14),22-二烯-3β,7α-二醇(9)、(22E,24R)-麦角甾-7,22-二烯-3β-醇(10)。除化合物9外其它化合物均为首次从以上相应毒菌中分离得到。     

苏铁的化学成分研究

对苏铁(Cycas revoluta)的化学成分进行研究,采用多种色谱技术(硅胶、氧化铝和Sephadex LH-20等)从苏铁茎的乙酸乙酯部位分离得到16个化合物,其结构由HR-ESI-MS、1H和13CNMR等波谱学方法鉴定为5,6-去氢柳杉酚(1)、cunningine A (2)、6-羟基-5,6-去氢柳杉酚(3)、6α-羟基-7-氧代弥罗松酚(4)、ligballinol (5)、xanthoxyol (6)、callislignan A (7)、(2R,3R)-bis[(4-hydroxy-3-methoxyphenyl) methyl]-1,4-diacetate (8)、开环异落叶松脂醇(9)、二氢山柰酚(10)、4'-甲基木犀草素(11)、5-methoxypinosylvin (12)、N-benzoylphenyl alaninol(13)、(E,4R)-4-hydroxy-4,5,5-trimethyl-3-(3-oxobut-1-enyl) cyclohex-2-enone (14)、3-hydroxy-5α,6α-epoxy-β-io-none (15)和acuminantin (16)。以上化合物均为首次从苏铁属植物中分离得到,其中化合物13和16为首次以天然产物报道。本研究还首次发现了苏铁属植物中含有松香烷型二萜类(1～4)和芪类(12)化合物。化合物11具有中等的体外α-葡萄糖苷酶抑制活性。     

New chemical constituents from the endophyte Streptomyces species LR4612 cultivated on Maytenus hookeri

From solid cultures of the biologically important endophyte Streptomyces species LR4612, cultivated on Maytenus hookeri, four new and two known compounds were isolated. The new compounds were identified as (2S*,3S*)-5-amino-3-hydroxy-5-oxopentan-2-yl 3-(formylamino)-2-hydroxybenzoate (1), N-[(3R*,4R*)-3-amino-3,4-dihydro-4-methyl-2,6-dioxo-2H,6H-1,5-benzodioxocin-10-yl]formamide (2), (5beta,6alpha)-6,11-dihydroxyeudesmane (3), and 5-(6,7-dihydroxy-6-methyloctyl)furan-2(5H)-one (4); the known compounds were elucidated as sorbicillin (5) and N-acetyltyramine (6). The structures were established by HR-ESI-MS and in-depth NMR analyses.     

Synthesis and biological evaluation of 1,3-oxathiolane 5-azapyrimidine, 6-azapyrimidine, and fluorosubstituted 3-deazapyrimidine nucleosides

(2R,5S)-5-Amino-2-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]- 1,2,4-triazine-3(2H)-one (8) and (2R,5R)-5-amino-2-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2,4-tr iazine-3(2H)-one (9) have been synthesized via a multi-step procedure from 6-azauridine. (2R,5S)-4-Amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,3, 5-triazine-2(1H)-one (11) and (2R,5R)-4-amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]- 1,3,5-triazine-2(1H)-one (12), and the fluorosubstituted 3-deazanucleosides (19-24) have been synthesized by the transglycosylation of (2R,5S)-1-[2-[[(tert-butyldiphenylsilyl) oxy]methyl]-1,3-oxathiolan-5-yl] cytosine (2) with silylated 5-azacytosine and the corresponding silylated fluorosubstituted 3-deazacytosines, respectively, in the presence of trimethylsilyl trifluoromethanesulfonate as the catalyst in anhydrous dichloroethane, followed by deprotection of the blocking groups. These compounds were tested in vitro for cytotoxicity against L1210, B16F10, and CCRF-CEM tumor cell lines and for antiviral activity against HIV-1 and HBV.     

Triterpenes and lignans from the leaves of Styrax tonkinensis

Two triterpenes (1 and 2) and eight lignans (3–10) were isolated from the ethyl acetate-soluble fraction of the leaves of Styrax tonkinensis (Pierre) Craib ex Hartw (Styracaceae). Their structures were established as ursolic acid (1), pomolic acid (2), 3,3′-bis(3,4-dihydro-6-methoxy-2H-1-benzopyran) (3), rac-(8α,8′β)-4,4′-dihydroxy-3,3′-dimethoxylignan-9,9′-diyldiacetate (4), (-)-secoisolariciresinol (5), (+)-pinoresinol (6), 4,4′-dihydroxy-3,3′-dimethoxy-9-ethoxy-9,9′-epoxylignan (7), (2S,3R, 4R)-4-[1-ethoxy-1-(4-hydroxy-3-methoxy)phenyl]methyl-2-(4-hydroxy-3-methoxy)phenyl-3-hydroxymethyl-tetrahydrofuran (8), (-)-neo-olivil-(9-O-9″)-seco-isolariciresinol (9) and isolariciresinol (10) based on MS, ¹H-and ¹³C-NMR spectral data. All these compounds (1–10) were firstly isolated from this plant, and compounds 2–5 and 7–9 were reported from the Styrax genus for the first time. Furthermore, the chemotaxonomic significance of the isolated compounds was discussed.     

New bisabolane sesquiterpenes and coumarin from Leontopodium longifolium

From the roots of Leontopotium longifolium, three new bisabolane sesquiterpenes, rel-(1S,4R,5S,6R)-4,5-diacetoxy-6-[(R)-1,5-dimethylhexa-3,5-dienyl]-3-methylcyclohex-2-enyl (Z)-2-methylbut-2-enoate (1), rel-(1S,4R,5S,6R)-4,5-diacetoxy-6-[(R)-5-hydroxy-1,5-dimethylhex-3-enyl]-3-methylcyclohex-2-enyl (Z)-2-methylbut-2-enoate (2), rel-(1R,2S,4R,5S)-4-acetoxy-2-[(R)-5-hydroxy-1,5-dimethylhex-3-enyl]-5-methylcyclohexyl (Z)-2-methylbut-2-enoate (3), and a new coumarin, 2,3-dihydro-5-hydroxy-2-(1-methylethenyl)-7H-pyrano[2,3-g][1,4]benzodioxin-7-one (4) together with nine known compounds have been isolated. The structures of these compounds were established by spectroscopic methods. Compounds 1 and 2 exhibited moderate cytotoxic activities against human promyelocytic leukemia (HL-60) cells.     

槐庶尺蛾性信息素腺体EAG活性成分绝对构型的鉴定(英文)

槐庶尺蛾Semiothisa cinerearia Bremer et Grey （鳞翅目： 尺蛾科）是我国北方国槐Sophora japonica L.上的重要食叶害虫。本研究的主要目的是阐明槐庶尺蛾性信息素成分化学结构的绝对构型, 为在城市地区环境友好地防控槐庶尺蛾的为害提供一种新方法。经与标准品比较气相色谱保留时间和质谱特征离子, 从槐庶尺蛾处女雌蛾（2-3日龄）性信息素腺体溶剂提取物中检测到顺6, 顺9-顺-3, 4-环氧-十七碳二烯烃和顺3, 顺6, 顺9-3, 6, 9-十七碳三烯烃2种成分, 在腺体中以100∶4.8±1.3 （N=12）的比例存在。槐庶尺蛾性信息素腺体提取物进一步经手性毛细管色谱柱（CycloSil-B, 30 m×0.25 mm×0.25 μm 液膜厚）分离, 在优化的程序升温条件下发现腺体成分顺6, 顺9-顺-3, 4-环氧-十七碳二烯烃具有3R, 4S的绝对构型。两种合成的对映异构体混合物顺6, 顺9-3R, 4S-环氧-十七碳二烯烃和顺6, 顺9-3S, 4R-环氧-十七碳二烯烃以1.28∶1的比例加到腺体提取物中, 比例变为1.55∶1。根据这一分析, 腺体成分顺6, 顺9-顺-3, 4-环氧-十七碳二烯烃进一步确认具有3R, 4S的绝对构型。该研究结论将为生产上研发高效的槐庶尺蛾性信息素诱芯奠定坚实的基础。     

小金梅草化学成分研究(英文)

从小金梅草乙醇提取物中分离得到了12个化合物,分别为3-O-β-D-槲皮素葡萄糖苷(1)、3-O-β-D-山柰酚葡萄糖苷(2)、5-O-β-D-芹菜素葡萄糖苷(3)、α-菠甾醇(4)、2,6-二甲氧基苯甲酸(5)、3-吲哚甲酸(6)、(2S,3R,4E,8E)-1-(β-D-吡喃葡萄糖苷)-N-[(R)-2’-羟基-二十碳酰基]-9-甲基-4,8-二烯-1,3-二醇-2-氨基-十八烷(7)、正三十二烷醇(8)、14,15-二十碳烯酸(9)、木腊酸(10)、β-谷甾醇(11)、胡萝卜苷(12)。以上化合物均为首次从该植物中得到。     

Extractive compounds of betulaceae family birch buds (Betula pendula Roth.): IV. Composition of sesquiterpene diols, triols, and flavonoids

This report is devoted to study of the hydrocarbon composition of the extract of buds of birch (family Betulaceae). We identified 3,5-dihydroxy-7,4??-dimethoxyflavone, 5,7-dihydroxy-3,4??-dimethoxyflavone, 7-methoxy-4??,5-dihydroxyflavanone, 4??-methoxy-5,7-hydroxyflavanone, 5??,6??-dihydroxycaryophyllen-4(14),8(15)-diene ((1R,5R,6R,9S)-5,6-dihydroxy-11,11-dimethyl-4,8-methylenebicyclo[7.2.0]-undecane), 5??,6??-dihydroxycaryophyllen-3,8(15)-diene ((1R,5R,6R,9S)-5,6-dihydroxy-11,11-dimethyl-8-methylenebicyclo[7.2.0]undec-3-ene), 6??,9??-dihydroxy-??-humulene((1E,4E,6R,9S)-6,9-dihydroxy-4,11,11-trimethyl-8-methylene-1,4-cycloundecanediene), 5??,6??,8??-trihydroxycariolan, and (1R,5R,6R,8R,9S)-trihydroxycariolan. The gas chromatographic retention indices of all identified compounds were determined.