Discovery of Four New Compounds from Macropanax membranifolius and Their Cytotoxic Activity

A phytochemical investigation of the methanolic extract of the Macropanax membranifolius C.B. Shang leaves led to the isolation of three new flavans, (2R,3R)-4′-O-methylcatechin 5-O-β-D-glucopyranoside ( 1 ), (2S,3S)-4′-O-methylcatechin 5-O-β-D-glucopyranoside ( 2 ), (2S,3R)-4′-O-methylcatechin 5-O-β-D-glucopyranoside ( 3 ), one new triterpene glycoside 3-O-β-D-xylopyranosyl-(1→6)-[β-D-xylopyranosyl-(1→2)]-β-D-glucopyranosyl-oleanolic acid 28-O-β-D-glucopyranoside ( 4 ), together with nine known compounds ( 5 - 13 ). Their chemical structures were elucidated based on HR-ESI-MS, NMR spectroscopic data. The absolute configurations of compounds 1 – 3 were established by electronic circular dichroism (ECD) spectra. At concentration of 20 μM, compounds 1 – 13 showed the percentages of dead cell in the range of 2.14 % to 33.61 % against KB, HepG2, HL60, P388, HT29, and MCF7 cancerous cell lines by SRB assay.     

New Amides from Buckwheat Seeds (Fagopyrum esculentum Moench)

Two new amino acid amides which yield in acid hydrolysis isomeric hydroxybenzylamines and amino acids have been isolated from the achenes of Fagopyrum esculentum Moench. One of them called BN-II is composed of salicylamine and allo-4-hydroxy-l-glutamic acid, and the other, BN-III, p-hydroxybenzylamine and l-glutamic acid. These coupled compounds link one another to form an amide respectively. Finally the structures of BN-II and BN-III were determined to be N⁵-(2′-hydroxybenzyl)-allo-4-hydroxy-l-glutamine and N⁵-(4′-hydroxybenzyl)-l-glutamine respectively from their chemical and spectrometry properties.     

Ionylideneacetic Acids and Abscisic Acid Biosynthesis by Cercospora rosicola

Several compounds having the basic α-ionylideneacetic acid structure were tested in Cercospora rosicola resuspensions. At 100 μm, all the compounds inhibited abscisic acid (ABA) biosynthesis. Time studies with unlabelled and deuterated (2Z,4E)- and (2E,4E)-α-ionylideneacetic acids showed rapid conversions into both (2Z,4E)- and (2E,4E)-4′-keto-α-ionylideneacetic acids as major products. Incorporation of the label into ABA was specific for the 2Z,4E-isomer. Minor products, identified by GC-MS, were (2Z,4E)- and (2E,4E)-4′-hydroxy-α-ionylideneacetic acids and (2Z,4E)-1′-hydroxy-α-ionylideneacetic acid. The conversion to (2Z,4E)-l′-hydroxy-α-ionylideneacetic acid has not been previously reported and was specific for the 2Z,4E-isomer. A time study for the conversion of methyl esters of [²H₃]-(2Z,4E)- and [²H₃]-(2E,4E)-4′-keto-α-ionylideneacetates showed a slow introduction of the l′-hydroxyl group and specificity for 2Z,4E-isomer. Conversion of the ethyl esters of (2Z,4E)- and (2E,4E)-l′-hydroxy-α-ionylideneacetates into the ethyl esters of both ABA and (2E,4E)-ABA demonstrated that ABA can be formed by oxidation of the 4′-position after the insertion of the 1′-hydroxy group. The ethyl 1′-hydroxy acids were also isomerized to the corresponding ethyl (2Z,4E)- and ethyl (2E,4E)-3′-hydroxy-β-ionylideneacetates. Ethyl (2Z,4E)-1′-hydroxy acid also gave small amounts of ethyl l′,4′-trans-diol of ABA. These results suggest that ABA may be formed through a (2Z,4E)-1′-hydroxy-α-ionylidene-type intermediate in addition to the previously proposed route through (2Z,4E)-4′-keto-α-ionylideneacetic acid.     

红背山麻杆叶的化学成分研究(Ⅲ)—奎宁酸类化合物

红背山麻杆作为一种常用的传统中药材,它常常被用来治疗前列腺、腰腿痛、炎症等疾病,它的化学成分及抗氧化活性已有研究报道。为了继续研究红背山麻杆的化学成分,以掌握其物质基础,对新鲜叶子80％丙酮提取物水萃取部位,利用凝胶、MCI及Toyopearl Butyl-650C柱色谱进行分离、纯化得到5个奎宁酸类化合物。根据化合物的波谱数据分析鉴定为3-O-咖啡酰基奎宁酸(1)、4-O-咖啡酰基奎宁酸(2)、5-O-咖啡酰基奎宁酸(3)、4-O-galloylquinic acid(4)、5-O-galloylquinic acid(5)。化合物1~5均为首次从本属植物中分离得到。通过抗氧化能力指数检测(ORAC法),所有的化合物均表现出较强的抗氧化活性。     

红背山麻杆叶的化学成分研究(Ⅰ)——酚酸类及相关化合物

采用80%丙酮提取石油醚萃取部位,利用凝胶、MCI及Toyopearl Butyl-650C柱色谱进行分离纯化得到10个酚酸类及相关化合物。根据化合物的波谱数据分析鉴定为水杨酸(1)、对羟基苯甲酸(2)、2,5-二羟基苯甲酸(3)、3,4-二羟基苯甲酸(4)、反-对香豆酸(5)、顺-对香豆酸(6)、咖啡酸(7)、咖啡酸甲酯(8)、没食子酸(9)、没食子酸甲酯(10)。其中化合物1~8、10均为首次从本属植物中分离得到。     

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.     

Synthesis of New 5″-Sulfonylamido Derivatives of 3″-Azido-3″-Deoxythymidine (AZT)

Abstract

A series of 5′-N-methanesulfonyl derivatives of 3′-azido-5′-(alkylamino)-3′,5′-dideoxythymidine was synthesised. The first step of the synthesis involved the reaction of 1-(2,5-dideoxy-5-O-tosyl-β-D-threo-pentofuranosyl)thymine 1 with an appropriate amine to give 1-[5-(alkylamino)-2,5-dideoxy-β-D-threo-pentofuranosyl]thymines 2a-e and 1-(2,5-dideoxy-β-threo-pent-4-enofuranosyl)thymine 3 as a by-product. Compounds 2a-e were treated with an excess of methanesulfonyl chloride to yield intermediates 1-[5-(dimethylamino)-3-O-methanesulfonyl-2,3,5-trideoxy-β-D-threo-pentofuranosyl]-thymine 4a and 1-[5-(N-alkyl-N-methanesulfonyl)-3-O-methanesulfonyl-2,3,5-trideoxy-β-D-threo-penfuranosyl]thymines 4b-e. The reaction of 4a-e with lithium azide in dimethyl-formamide afforded the final compounds 1-[3-azido-5-(N-methyl-N-methanesulfonyl)-2,3,5-trideoxy-β-D-erythro-penofuranosyl]thymine 5a and 1-[3-azido-5-(N-alkyl-N-methanesulfonyl)-2,3,5-trideoxy-β-D-erythro-penofuranosyl]thymines 5b-e. The independent synthesis of 4′,5′-unsaturated product 3 was also described.     

Two New Chromone Glycosides from the Roots of Saposhnikovia divaricata

Five chromone glycosides were isolated from the water‐soluble portions of 70% EtOH extract of the roots of Saposhnikovia divaricata, including two new chromone glycosides 1 and 2 . The structures of the chromone glycosides were identified as (3′S)‐3′‐O‐β‐d ‐apiofuranosyl‐(1 → 6)‐β‐d ‐glucopyranosylhamaudol ( 1 ), (2′S)‐4′‐O‐β‐d ‐apiofuranosyl‐(1 → 6)‐β‐d ‐glucopyranosylvisamminol ( 2 ), 3′‐O‐glucopyranosylhamaudol ( 3 ), 4′‐O‐β‐d ‐glucopyranosylvisamminol ( 4 ), and 4′‐O‐β‐d ‐glucopyranosyl‐5‐O‐methylvisamminol ( 5 ) on the basis of extensive spectroscopic methods, and the absolute configurations of the new compounds were elucidated by the electronic circular dichroism (ECD) calculation and acid hydrolysis. The cytotoxic activities of the glycosides 1 – 5 against three human cancer cell lines (PC‐3, SK‐OV‐3, and H460) were evaluated. The result showed that compounds 1 – 5 had weak cytotoxic activities against the human cancer cell lines with IC₅₀ values in the range of 48.54 ± 0.80 – 94.25 ± 1.45 μm .     

Nucleosides VI: A Novel and Convenient Synthesis of Purine S-Cyclonucleosides Via Mitsunobu Reaction

Abstract

Two representative S-cyclonucleosides, 8,5′-anhydro-2′, 3′-O-isopropylidene-8-mercaptoadenosine (3) and 8,2′-anhydro-3′,5′-O-(tetraisopropyldisiloxane-1,3-diyl)-8-mercaptoguanosine (8), were prepared in good yields by dropwise addition of one equivalent each of triphenylphosphine and DEAD in DMF into a mixture of 2′,3′-O-isopropylidene-8-mercaptoadenosine (2) or 3′,5′-O-(tetra-iso-propyldisiloxane-1,3-diyl)-8-mercaptoguanosine (7), respectively, in DMF. Treatment of compound 2 with two equivalents each of triphenylphosphine and DEAD in DMF afforded N-[8,5′-anhydro-2′,3′-O-isopropylidene-8-mercaptopurin-6-yl]triphenylphospha-λ5-azene (4) in 87% yield.     

Differential Effect of Selected Phenoxy-acid Compounds on Oxidative Phosphorylation of Mitochondria from Vicia faba L.

The effect of six phenoxy-acid herbicides, 4-chloro-2-methylphenoxyaceticacid (MCPA), 4-(4-chloro-2-thylphenoxy)butyric acid (MCPB),2, 4-dichlorophenoxyacetic acid (2, 4-D), 4-(2, 4-dichlorophenoxy)butyricacid (2, 4-DB), 2, 4, 5-trichlorophenoxyacetic acid (2, 4, 5-T),and 4-(2, 4, 5-trichlorophenoxy)butyric acid (2, 4, 5-TB) onoxidative phosphorylation of mitochondria isolated from younghypocotyls of Vicia faba L. has been investigated. When NADHwas used as substrate all the test herbicides were found tostimulate state 4 respiration with the loss of phosphorylationand respiratory control in varying degrees. When malate andsuccinate were used separately as substrates, treatment with2, 4-DB, 2, 4, 5-T, and 2, 4, 5-TB at low concentration resultedin a marked stimulation of state 4 respiration; this effectwas not obtained with MCPA, MCPB, or 2, 4-D. At higher concentrationsall herbicides strongly inhibited respiration. These compoundsreleased oligomycin inhibition during NADH oxidation in varyingdegrees, stimulated mitochondrial adenosine-triphosphatase activity,and induced swelling of isolated mitochondria. In many respectsand in differing degrees they resemble 2, 4-dinitrophenol (DNP)in their action as uncouplers. Phenoxy-butyric acids were foundto be more toxic in vitro as uncouplers than their correspondingphenoxyacetic acids. Phenoxyacetic acids were very active as uncouplers in vivo whilephenoxybutyric acids had negligible effect. It is concludedthat in vivo, non-activity of phenoxybutyric acids is due totheir restricted entry into plants and that if available atthe site of action they would be inherently toxic.     

New metabolites from the alga-derived fungi Penicillium thomii Maire and Penicillium lividum Westling

A new meroterpenoid, austalide H acid ethyl ester (1), 5-(2′,4′-dihydroxy-6′-methylphenyl)-3-methylfuran-2-carboxylic acid (2), 5-(2′-hydroxy-6′-methylphenyl)-3-methylfuran-2-carboxylic acid (3) and 5-((6′-methyl-4′-oxo-3′,4′-dihydro-2H-pyran-2′-yl)methyl)-3-methylfuran-2-carboxylic acid (4), along with six known compounds, austalides H, J, K, and P (5–8), questin (9) and sulochrin (10) were isolated from the lipophilic extract of the alga-derived fungi Penicillium thomii KMM 4645 and Penicillium lividum KMM 4663. The structures of the isolated compounds were determined based on spectroscopic methods. The austalides showed significant inhibitory activity against endo-1,3-β-d-Glucanase from a crystalline stalk of the marine mollusk Pseudocardium sachalinensis.     

Cometabolism of 3-methylbenzoate and methylcatechols by a 3-chlorobenzoate utilizingPseudomonas: Accumulation of (+)-2,5-dihydro-4-methyl-and (+)-2,5-dihydro-2-methyl-5-oxo-furan-2-acetic acid

Summary 3-Chlorobenzoate grown cells ofPseudomonas strain B 13 readily co-oxidize 3-methylbenzoate yielding 82% (+)-2,5-dihydro-4-methyl- and 9% (+)-2,5-dihydro-2-methyl-5-oxo-furan-2-acetic acid (compounds I and II, X=CH₃). The concentration of the products in the culture fluid exceed 11 g per liter without affecting the activity of the cells. The products were formed in 89% and 93% yield when 3- or 4-methylcatechol is cometabolized correspondingly. The lactonization of methyl- and halomuconic acids is discussed with regard to the mechanism of halide elimination during utilization of chlorosubstituted aromatic compounds.     

Cyclopaldic Acid,Seiridin, and Sphaeropsidin A as Fungal Phytotoxins,and Larvicidal and Biting Deterrents against Aedes aegypti (Diptera: Culicidae): Structure?Activity Relationships

Aedes aegypti L. is the major vector of the arboviruses responsible for dengue fever, one of the most devastating human diseases. From a preliminary screening of fungal phytotoxins, cyclopaldic acid ( 1 ), seiridin ( 2 ), sphaeropsidin A ( 4 ), and papyracillic acid ( 5 ) were evaluated for their biting deterrent and larvicidal activities against Ae. aegypti L. Because compounds 1, 2, 4 , and 5 exhibited mosquito biting deterrent activities and 1 and 4 demonstrated larvicidal activities, further structure? activity relationship studies were initiated on these toxins. In biting‐deterrence bioassays, 1, 2, 4 , and 5 , 3,8‐didansylhydrazone of cyclopaldic acid, 1F , 5‐azidopentanoate of cyclopaldic acid A, 1G , the reduced derivative of cyclopaldic acid, 1 H , isoseiridin ( 3 ), 2′‐O‐acetylseiridin ( 2A ), 2′‐oxoseiridin ( 2C ), 6‐O‐acetylsphaeropsidin A ( 4A ), 8,14‐methylensphaeropsidin A methyl ester ( 4B ), and sphaeropsidin B ( 4C ) showed activities higher than the solvent control. Sphaeropsidin B ( 4C ) was the most active compound followed by 2A , while the other compounds were less active. Biting‐deterrence activity of compound 4C was statistically similar to DEET. In the larvicidal screening bioassays, only compounds 1 and 4 demonstrated larvicidal activities. Based on LD₅₀ values, compound 4 (LD₅₀ 36.8 ppm) was significantly more active than compound 1 (LD₅₀ 58.2 ppm). However, the activity of these compounds was significantly lower than permethrin.     

Purification and Properties of β-Galactosidases from Bacillus circulans

Six compounds, Z- and E-fadyenolide (3, 4), 1-ally1-2,3-(methylenedioxy)-4,5-dimethoxy-benzene (5), 4-methoxy-3,5-bis (3′-methyl-2′-butenyl)-benzoic acid (6), 2,6-dihydroxy-4-methoxy-dihydrochalcone (7), and 5-hydroxy-7-methoxyflavanone (8) were isolated from three species of Jamaican Piper, Piper fadyenii, C.D.C., Piper aduncum L. and Piper hispidum Sw. Three amides (9 ~ 11) of 3,5-dimethoxy-4-oxo-5-phenylpent-2-enoic acid using piperidine, pyrrolidine and morpholine, respectively, were synthesized from compounds 3 and 4, and tested for insecticidal activity against the tick Boophilus microplus (Canestrini) and the flour feetle, Tribolium confusum Duval. In our experiment, compounds 9 ~ 11 inhibited ovogenesis of B. microplus and were toxic to T. confusum. Compounds 3 ~ 8 were found to have no activity.     

Asymmetric Synthesis of α-Methylglutamic Acid and α-Methylornithine by a Chiral Isocyano Amide Reagent

An efficient approach to the asymmetric syntheses of α-methylglutamic acid and α-methylornithine is described. Two chiral reagents, (2′S)-N-(2′-methoxymethylpyrrolidine)-2-isocyanopropionamide 4 and (2′S)-N-(2′-hydroxymethylpyrrolidine)-2-isocyanopropionamide 5, were employed for the asymmetric induction. α-Methylglutamic acid 7 was synthesized by the asymmetric Michael-addition of methyl acrylate to 4 and 5 as the key step. The optical yield of 7 was 10~45% (R-form). α-Methylornithine 12 was also synthesized by the reaction of 4 with acrylonitrile as the key step. The optical yield of 12 was 31.7% (R-form).     

Mitsunobu Reactions of 5‐Fluorouridine with the Terpenols Phytol and Nerol: DNA Building Blocks for a Biomimetic Lipophilization of Nucleic Acids

The cancerostatic 5‐fluorouridine (5‐FUrd; 1 ) was sequentially sugar‐protected by introduction of a 2′,3′‐O‐heptylidene ketal group (→ 2 ), followed by 5′‐O‐monomethoxytritylation (→ 3 ). This fully protected derivative was submitted to Mitsunobu reactions with either phytol ((Z and E)‐isomer) or nerol ((Z)‐isomer) to yield the nucleoterpenes 4a and 4b . Both were 5′‐O‐deprotected with 2% Cl₂CHCOOH in CH₂Cl₂ to yield compounds 5a and 5b , respectively. These were converted to the 5′‐O‐cyanoethyl phosphoramidites 6a and 6b , respectively. Moreover, the 2′,3′‐O‐(1‐nonyldecylidene) derivative, 7a , of 5‐fluorouridine was resynthesized and labelled at C(5′) with an Eterneon‐480 fluorophor^® (→ 7b ). The resulting nucleolipid was studied with respect to its incorporation in an artificial bilayer, as well as to its aggregate formation. Additionally, two oligonucleotides carrying terminal phytol‐alkylated 5‐fluorouridine tags were prepared, one of which was studied concerning its incorporation in an artificial lipid bilayer.     

Methyl Jasmonate and Lactones Including Jasmine Lactone in Ceylon Tea

The ester and lactone fraction possessing the most attractive aroma was separated from the aroma concentrate of Ceylon flavory tea by silica-gel column chromatography and analyzed by GC-MS.

Methyl 2-(cis-2′-pentenyl)-cyclopentanone-3-acetate(methyl jasmonate), 5-(cis-2′-pentenyl)-5-pentanolide (jasmine lactone), 2,3-dimethyl-2-nonen-4-olide, 4-octanolide, 4-nonanolide and 5-decanolide were newly identified as the constituents of tes aroma. Former two compounds seemed to carry a major share of aroma character of Ceylon flavory tea.     

Two Oxazolyl Compounds and a Monosubstituted α-Pyrone as Free-radical Scavengers Isolated from a Fungus

In the course of our screening for free radical scavengers, (1′E)-erythro-4-(3′,4′-dihydroxypentenyl)oxazole (1) (1′E,4′S)-4-(3′-oxo-4′-hydroxypentenyl)oxazole (2) and 6-pentyl-α-pyrone (3) were isolated from an unidentified fungal metabolite. These compounds, especially novel oxazolyl compound 2, inhibited the bactericidal effect of the Fenton reagent toward Bacillus subtilis. They and their acetylated compounds (diAc-1 and Ac-2) also showed inhibitory activity against linoleate autoxidation. Furthermore, 1–3 inhibited oxidative enzymes (soybean lipoxygenase and mushroom tyrosinase).

To investigate the radical scavenging mechanism of 3, two oxidized products (4 and 5) were isolated from the reaction mixture of 3 and the Fenton reagent. Compounds 4 and 5 seemed to be derived from 3 by scavenging the hydroxyl radical.     

Synthesis of the 2′-,3′-Didehydro-2′-,3′-dideoxy and 2′-,3′-Dideoxy Derivatives of 6-Azauridine and a New Route to 2′-,3′-Didehydro-2′-,3′-dideoxy-5-chlorouridine

Abstract

The 5′-O-(4,4′-dimethoxytrityl) and 5′-O-(tert-butyldimethylsilyl) derivatives of 2′-,3′-O-thiocarbonyl-6-azauridine and 2′,3′-O-thiocarbonyl-5-chlorouridine were synthesized from the parent nucleosides by reaction with 4, 4′-dimethoxytrityl chloride and tert-butyldimethylsilyl chloride, respectively, followed by treatment with 1,1′-thiocarbonyldiimidazole. Introduction of a 2′-,3′-double bond into the sugar ring by reaction of the 5′-protected 2′-,3′-O-thionocarbonates with 1, 3-dimethyl-2-phenyl-1, 3, 2-diazaphospholidiine was unsuccessful, but could be accomplished satisfactorily with trimethyl phosphite. Reactions were generally more successful with the 5′-silylated than with the 5′-tritylated nucleosides. Formation of 2′-,3′-O-thiocarbonyl derivatives proceeded in higher yield with 5′-protected 6-azauridines than with the corresponding 5-chlorouridines because of the propensity of the latter to form 2,2′-anhydro derivatives. In the reaction of 5′-O-(tert-butyldimethylsilyl)-2′-,3′-O-thiocarbonyl-6-azauridine with trimethyl phosphite, introduction of the double bond was accompanied by N³-methylation. However this side reaction was not a problem with 5′-O-(tert-butyldimethylsilyl)-2′-, 3′-O-thioarbonyl-5-chlorouridine. Treatment of 5′-O-(tert-butyldimethylsilyl)-2′-, 3′-didehydro-2′-,3′-dideoxy-6-azauridine with tetrabutylammonium fluoride followed by hydrogenation afforded 2′-,3′-dideoxy-6-azauridine. Deprotection of 5′-O-(tert-butyldimethylsilyl)-2′-, 3′-didehydro-2′-,3′-dideoxy-5-chlorouridine yielded 2′-,3′-didehydro-2′-,3′-dide-oxy-5-chlorouridine.     

Effect of Non-Volatile Constituents of Elsholtzia ciliata (Thunb.) Hyl. from Southern Vietnam on Reactive Oxygen Species and Nitric Oxide Release in Macrophages

The extract of Elsholtzia ciliata aerial parts was subjected to bio-guided isolation using the intercellular ROS reduction in J774A.1 macrophages to monitor the anti-oxidative activity. Fifteen compounds were isolated from the active fractions including eleven flavonoids (vitexin, pedalin, luteolin-7-O-β-d -glucopyranoside, apigenin-5-O-β-d -glucopyranoside, apigenin-7-O-β-d -glucopyranoside, chrysoeriol-7-O-β-d -glucopyranoside, 7,3′-dimethoxyluteolin-6-O-β-d -glucopyranoside, luteolin, 5,6,4′-trihydroxy-7,3′-dimethoxyflavone, 5-hydroxy-6,7-dimethoxyflavone (compound 13 ), 5-hydroxy-7,8-dimethoxyflavone); three hydroxycinnamic acid derivatives (caffeic acid, 4-(E)-caffeoyl-l -threonic acid, 4-O-(E)-p-coumaroyl-l -threonic acid) and one fatty acid (α-linolenic acid). The biological evaluation of these compounds (10–2.5 μm ) indicated that all of them exerted good antioxidant and anti-inflammatory activities, in particular compound 13 .