Curcumin and its analogues as potent inhibitors of low density lipoprotein oxidation: H-atom abstraction from the phenolic groups and possible involvement of the 4-hydroxy-3-methoxyphenyl groups

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, 1) is a yellow ingredient isolated from turmeric (Curcumin longa). It has been shown to exhibit a variety of biological activities including antioxidative activity. In order to find more active antioxidants with 1 as the lead compound we synthesized curcumin analogues, i.e., 1,7-bis(3,4-dihydroxyphenyl)-1,6-heptadiene-3,5-dione (2), 1-(3,4-dihydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (3), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (4), 1,7-bis (4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (5), 1-(3,4-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (6), 1,7-bis(3,4-dimethoxyphenyl)-1,6- heptadiene-3,5-dione (7), 1,7-bis(4-methoxyphenyl)-1,6-heptadiene-3,5-dione (8), and 1,7-diphenyl-1,6-heptadiene-3,5-dione (9). Antioxidative effects of curcumin and its analogues against free radical initiated peroxidation of human low density lipoprotein (LDL) were studied. The peroxidation was initiated either by a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), or by cupric ion (Cu2+). The reaction kinetics were monitored either by the uptake of oxygen and the depletion of alpha-tocopherol present in the native LDL, or by the formation of thiobarbituric acid reactive substances. Kinetic analysis of the antioxidation process demonstrates that these compounds, except 7, 8, and 9, are effective antioxidants against AAPH- and Cu2+ -initiated LDL peroxidation by H-atom abstraction from the phenolic groups. Compounds 2 and 3 which bear ortho-diphenoxyl functionality possess significantly higher antioxidant activity than curcumin and other analogues, and the 4-hydroxy-3-methoxyphenyl group also play an important role in the antioxidative activity.     

柯拉斯那沉香中2-(2-苯乙基)色酮类化学成分研究

为研究柯拉斯那(Aquilaria crassna Pierre ex Lecomte)沉香的化学成分。实验采用多种柱色谱方法从该沉香中分离得到9个2-(2-苯乙基)色酮类化合物,通过现代波谱学技术分别鉴定为6-甲氧基-2-[2-(3′-羟基-4′-甲氧基苯基)乙基]色酮(1)、5-羟基-6-甲氧基-2-[2-(3′-羟基-4′-甲氧基苯基)乙基]色酮(2)、tetrahydrochromone F(3)、6-甲氧基-2-[2-(3′-甲氧基-4′-羟基苯基)乙基]色酮(4)、6-甲氧基-7-羟基-2-[2-(4′-甲氧基苯基)乙基]色酮(5)、6,7-二甲氧基-2-[2-(3′-羟基-4′-甲氧基苯基)乙基]色酮(6)、6,7-二甲氧基-2-[2-(4′-甲氧基苯基)乙基]色酮(7)、6-羟基-2-[2-(4′-羟基苯基)乙基]色酮(8)、5-羟基-2-[2-(2′-羟基苯基)乙基]色酮(9)。化合物2、3和5～9均为首次从柯拉斯那所得沉香中分离得到。采用MTT法对单体化合物的细胞毒活性进行测试,测试结果表明,化合物1,2和4具有微弱的细胞毒活性。     

Investigations on the influence of terminal groups at the C2-propyl side chain of 1,1-bis(4-hydroxyphenyl)-2-phenylpent-1-ene and 1,1,2-tris(4-hydroxyphenyl)pent-1-ene on the estrogen receptor binding and the estrogenic/anti-estrogenic properties

1,1-bis(4-Hydroxyphenyl)-2-phenylpent-1-ene (5) and 1,1,2-tris(4-hydroxyphenyl)pent-1-ene (6) derivatives with terminal CN (5a, 6a), NH(2) (5b, 6b), NHCOCH(3) (5c, 6c), NHCOC(2)H(5) (5d, 6d) groups at the C2-propyl chain were synthesized and assayed in vitro for estrogen receptor (ER) binding affinity (RBA) in a competition experiment with [3H]estradiol and for estrogenic and anti-estrogenic properties in a luciferase assay with ER-positive MCF-7-2a cells, stably transfected with the plasmid ERE(wtc)luc. The CN as well as the NH(2) group reduced the RBA-values (5: 2.09%; 5a: 1.50%; 5b: 0.07%; 6: 4.03%; 6a: 0.67%; 6b: 0.20%) and the antagonistic potency (5: IC(50)=0.05 microM; 5a: IC(50)=0.43 microM; 5b: IC(50)=1.50 microM; 6: IC(50)=0.07 microM; 6a: IC(50)=0.60 microM; 6b: IC(50)=2.00 microM). Derivatization of the amino function with acetic anhydride and propionic anhydride did not change the RBA-value but altered the antagonistic profile (5c: IC(50)=2.50 microM; 5d: IC(50)=not detectable; 6c: IC(50)=0.65 microM; 6d: IC(50)=1.00 microM). Agonistic effects were only detected for the amine 6b (34.2% activation of the luciferase expression). These data document that estrogen receptor binding and the antagonistic effects can be modified by terminal groups at the C2-propyl chain of the pure antagonists 5 and 6. The mode of action is unclear. However, it can be assumed that the elongation of the side chain causes a reorientation in the LBD in order to locate the side chain in a side pocket near the ligand binding domain.     

Rapid synthesis of 4-benzylidene and 4-[bis-(4-methoxyphenyl)-methylene-2-substituted phenyl-benzopyrans as potential selective estrogen receptor modulators (SERMs) using McMurry coupling reaction

7-Methoxy-4-(4-methoxybenzylidene)-2-substituted phenyl-benzopyrans I and 4-[bis-(4-methoxyphenyl)-methylene-2-substituted phenyl-benzopyrans II carrying different alkylamino residues, designed as estrogen receptor (ER) binding ligands, were successfully synthesized through the McMurry coupling reaction of substituted benzaldehyde/substituted benzophenones and 2-hydroxyphenyl-7-methoxy-chroman-4-one in presence of lithium aluminum hydride and titanium (IV) chloride (LAH-TiCl(4)). Self-coupling of carbonyl reactants led to the formation of several side products. The prototypes were evaluated for their relative binding affinity (RBA), as well as their estrogenic and antiestrogenic activities. High order of estrogenic activity (>50% gain) observed with compounds 3, 7a, 7b, 7c, 8, and 10a and also their partial estrogen antagonistic activity (> or =15%) at the uterine level points toward successful designing of the compounds. Compounds 4, 7a, 7b, 7c, and 10a also possessed significant anticancer activity against human adenocarcinoma cell line (MCF-7 cell line) that may be related to their estrogen-dependent action.     

New Withanolides from Nicandra physaloides (Solanaceae)

Two new withanolides, named nicandrenone methyl ether (1), 26S nicandrenone methyl ether (2), together with ten known compounds were isolated from the whole plants of Nicandra physaloides (Solanaceae). Their chemical structures were deduced on the basis of spectroscopic analysis. Ten known compounds were identified as nicandrenone (3), Nic-7 (4), nicaphysalin E (5), pinosylvin monomethyl ether (6), 2S-pinocembrin (7), (1S, 2R)-1, 2-bis (4-hydroxy-3-methoxyphenyl)-1, 3-propanediol (8), vanillin (9), indole-3-carboxylic acid (10), vanillic acid (11) and drummondol (12).     

Bivalent ligand approach on 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine: synthesis and binding affinities for 5-HT(7) and 5-HT(1A) receptors

We here report on the synthesis and binding properties at 5-HT(7) and 5-HT(1A) receptors of ligands 3-12, that were designed according to the 'bivalent ligand' approach. Two moieties of the 5-HT(7)/5-HT(1A) ligand 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine (1) were linked through their 3-methoxy substituent by polymethylene chains of variable length, with the aim to increase the affinity for 5-HT(7) receptor and the selectivity over 5-HT(1A) receptors. In the best cases, the dimers showed affinities for 5-HT(7) receptors as high as the monomer with no improvement in selectivity. Some dimers displayed 5-HT(1A) receptor affinities slightly higher than monomer 1.     

Diarylheptanoids from the rhizomes of Zingiber officinale

Seven new diarylheptanoids, i.e., (3S,5S)-3,5-diacetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3-acetoxy-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3,5-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane, (5S)-5-acetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3-one, 5-hydroxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptan-3-one, 5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3,4-dihydroxy-5-methoxy-phenyl)heptan-3-one and 1,5-epoxy-3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane were isolated from the rhizomes of Chinese ginger (Zingiber officinale Roscoe), along with 25 known compounds, i.e., 8 diarylheptanoids, 14 gingerol analogs, a diterpene and 2 steroids. Their structures were elucidated by spectroscopic and chemical methods.     

Cytotoxic sesquiterpenes from Magnolia kachirachirai

Bioassay-guided fractionation of the root wood of Magnolia kachirachirai (Kanehira & Yamamoto) Dandy (Magnoliaceae) led to the isolation of three new compounds, kachiraterpenol (1), (E)-2,3-bis(4-hydroxy-3-methoxyphenyl)prop-2-enal (15), and kachiranol (19), together with 27 known compounds, of which 4,4'-dihydroxy-3,3'-dimethoxybenzophenone (16) was isolated for the first time from a natural source. Their structures were elucidated by spectroscopic analysis. Two of these isolates, costunolide (2) and dehydrosaussurea lactone (4), showed cytotoxic properties against MCF-7, NCI-H460, and SF-268 cancer cell lines in vitro.     

Identification of 2-[2-(acetylamino)-4-amino-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-4) as a potent mutagen in river water in Kyoto and Aichi prefectures, Japan

We have previously isolated five mutagens in blue rayon-adsorbed substances from water at a site below sewage plants in the Nishitakase River, in Kyoto, Japan, and identified two of them as 2-phenylbenzotriazole derivatives, 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-1) and 2-[2-(acetylamino)-4-[(2-cyanoethyl)ethylamino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2). In the present study, we collected adsorbed materials on blue cotton (3 kg x 9 times) at the same location, and isolated a sufficient amount (97 microg) of one of the remaining three mutagens other than PBTA-1 and PBTA-2, for structural analysis, by multiple column chromatography. The structure of mutagen, accounting for 12% of the total mutagenicity of the blue rayon-adsorbed substances, was determined to be a PBTA-1 analogue, 2-[2-(acetylamino)-4-amino-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-4). PBTA-4 is a potent mutagen, inducing 190,000 and 7,800,000 revertants of Salmonella typhimurium TA98 and YG1024 per microgram, respectively, in the presence of S9 mix. In addition to the water of the Nishitakase River, PBTA-4 was detected in water samples from two rivers that flow through other regions where textile-dyeing industries have been developed. Like other PBTA analogues, PBTA-4 might also be produced from azo dyes during industrial processes in dyeing factories and treatment at sewage plants.     

2-Phenyl-1-[4-(2-piperidine-1-yl-ethoxy)benzyl]-1H-benzimidazoles as ligands for the estrogen receptor: Synthesis and pharmacological evaluation

2-Phenyl-1H-benzimidazoles 7a–e were synthesized and tested for gene activation on ERα-positive MCF-7 breast cancer cells, stably transfected with the reporter plasmid ERE_wtcluc (MCF-7-2a cells). None of the compounds showed agonistic properties, but they antagonized dependent on hydroxyl groups at the benzimidazole core (5- or 6-OH) and at the aromatic ring in the 2-position (4-OH) in high concentrations the gene activation induced by estradiol (E2, 1 nM). All compounds exhibited significant antiproliferative properties on MCF-7 cells but they were inactive against hormone independent, ER negative MDA-MB-231 cells.     

柬埔寨柯拉斯那沉香的化学成分研究

该文采用ODS、硅胶、Sephadex LH-20等柱色谱技术,对柬埔寨野生柯拉斯那沉香(Aquilaria crassna)进行了研究。结果表明:从柬埔寨柯拉斯那所产沉香的乙醇提取物中进行分离共得到了10个化合物,包括一对对映异构体(9a/9b)。经波谱解析分别鉴定为6-甲氧基-2-[2-(3-羟基-4-甲氧基苯)乙基]色酮(1)、6-甲氧基-2-[2-(3-甲氧基-4-羟基苯)乙基]色酮(2)、6,7-二甲氧基-2-(2-苯乙基)色酮(3)、6-羟基-2-(2-苯乙基)色酮(4)、6-羟基-2-[2-(4-甲氧基苯)乙基]色酮(5)、8-氯-6-羟基-2-[2-(3-羟基-4-甲氧基苯)乙基]色酮(6)、8-氯-6-羟基-2-[2-(4-甲氧基苯)乙基]色酮(7)、oxidoagarochromone B(8)、4'-demethoxyaqusisnenone D(9)。其中,化合物6、7和9均为首次从柯拉斯那沉香中分离得到。活性测试结果显示,化合物1和2对乙酰胆碱脂酶具有一定的抑制活性,化合物2对人慢性髓原白血病细胞K562具有较弱的抑制作用。     

广东土牛膝的化学成分

广东土牛膝为菊科泽兰属植物华泽兰（Eupatorium chinense）的干燥根。从其甲醇提取物中共分离得到11个化合物,其中eupatorinA（1）为一新化合物,经波谱学方法鉴定为（threo）-3-O-acetyl-1-（4-hydroxy-3-methoxyphenyl）-2-[4-（3-hydroxy-1-（E）-propenyl）-2,6-dimethoxyphenoxy]propyl-β-D-glucopy-ranoside。已知化合物分别鉴定为（threo）-3-hydroxy-1-（4-hydroxy-3-methoxyphenyl）-2-[4-（3-hydroxy-1-（E）-propenyl）-2,6-dimethoxyphenox-y]-propyl-β-D-glucopyranoside（2）,ardisiacrispinA（3）,ardisiac-rispinB（4）,euparone（5）,3-（2,3-dihydroxy-isopen-tyl）-4-hydroxyacetophenone（6）,12,13-di-hydroxy-euparin（7）,gymnastone（8）,N-（2′-hydroxy-tetracosanosyl）-2-amino-1,3,4-trihydroxy-octa-dec-8-（E）-ene（9）,stigmasterol（10）和stigmasterol-3-O-β-D-glucopyranoside（11）。化合物2-4为首次从菊科植物,5-8为首次从泽兰属植物中分离得到。     

New azafluorenones with cytotoxic and carbonic anhydrase inhibitory properties: 2-Aryl-4-(4-hydroxyphenyl)-5H-indeno[1,2-b]pyridin-5-ones

New azafluorenones, 2-aryl-4-(4-hydroxyphenyl)-5H-indeno[1,2-b]pyridin-5-ones, were prepared to evaluate their cytotoxic/anticancer properties, also their inhibitory effects on hCA I and II isoenzymes. Aryl part was changed as [phenyl (H1), 4-methylphenyl (H2), 4-methoxyphenyl (H3), 4-fluorophenyl (H4), 4-bromophenyl (H5), 4-chlorophenyl (H6), 3-hydroxyphenyl (H7), and 4-hydroxyphenyl (H8)]. The structure of the synthesized compounds was characterized by ¹H NMR, ¹³C NMR and HRMS spectra.Cytotoxicity results of the series pointed out that the compounds H6 (PSE: 28.0) and H5 (PSE: 27.3), with the highest potency selectivity expression (PSE) value, can be considered as leader compounds of the study in designing novel anticancer agents. Additionally, all azafluorenones synthesized showed a good inhibition profile towards hCA I and II isoenzymes in the range of 54.14–73.72 nM and 67.28–76.15 nM, respectively.The compounds H5 and H6 can be considered for further designs with their cytotoxic and CA inhibitory profiles.     

宁夏枸杞根和茎的化学成分及抗炎活性研究

研究宁夏枸杞(Lycium barbarum L.)根部和茎部的化学成分。采用硅胶柱、ODS开放柱、Sephadex LH-20葡聚糖凝胶柱及半制备反相高效液相等色谱手段,对宁夏枸杞根和茎部乙醇提取物的石油醚部位及乙酸乙酯部位化学成分进行分离纯化,根据其理化性质以及波谱数据鉴定得到12个化合物,分别为N-[2-(3,4-dihydroxyphenyl)-2-hydroxyethyl]-3-(4-methoxyphenyl)prop-2-enamide(1)、3-(4-hydroxy-3-methoxy phenyl)-N-2-(4-hydroxyphenyl)-2-methoxyethyl]acrylamide(2)、N-trans-coumaroyloctopamine(3)、(E)-2-(4,5-dihydroxy-2-{3-[(4-hydroxyphenethyl)amino]-3-oxopropyl}phenyl)-3-(4-hydroxy-3,5-dimethoxyphenyl)-N-(4-acetamidobutyl)acrylamide(4)、1,2-dihydro-6,8-dimethoxy-7-hydroxy-1-(3,4-dihydroxy-phenyl)-N1,N2-bis[2-(4-hydroxyphenyl)ethyl]-2,3-naphthalene dicarboxamide(5)、(+)-syringaresinol(6)、zhebeiresinol(7)、(±)-eriodictyol(8)、isovanilin(9)、5,5′-dimethoxybiphenyl-2,2′-diol(10)、p-hydroxyphenethyltrans-ferulate(11)、E-ferulic acid hexacosyl ester(12),所有化合物均为首次从该植物中分离得到。此外,采用MTT法和抑制一氧化氮(NO)生成实验,从细胞毒活性和抗炎活性两方面评估了化合物的生物活性。结果表明,化合物2具有显著的抗炎活性,其IC50值(17.00±1.11μmol/L)小于阳性对照药槲皮素的IC50值(17.21±0.50μmol/L)。     

(Z)-1,1-dichloro-2-(4-benzyloxyphenyl)-2,3-bis(4-methoxyphenyl)cyclopropane: The synthesis and enantiomeric separation of an antitumor agent

(Z)-1,1-Dichloro-2-(4-benzyloxyphenyl)-2,3-bis(4-methoxyphenyl)cyclopropane ( 5 ), a potential antitumor agent designed to treat breast cancer, was prepared in three steps. A stereospecific palladium-catalyzed cross coupling reaction which provided the intermediate (Z)-triaryl alkene 4 was a crucial step in the synthesis. Makosza phase transfer reaction on 4 gave the enantiomeric (Z)-dichlorocyclopropane derivatives 5 which were resolved by semipreparative HPLC on a chiral stationary phase consisting of amylose tris-3,5-dimethylphenyl carbamate coated on silica gel. © 1994 Wiley-Liss, Inc.     

Inhibition of lipid peroxidation and protein oxidation in rat liver mitochondria by curcumin and its analogues

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, 1) is a yellow ingredient isolated from turmeric (curcumin longa). It has been shown to exhibit a variety of biological activities including antioxidative activity. In order to find more active antioxidants with 1 as the lead compound we synthesized curcumin analogues, i.e., 1-(3,4-dihydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (2), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (3), 1,7-bis-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (4), 1-(3,4-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (5), 1,7-bis(3,4-dimethoxyphenyl)-1,6-heptadiene-3,5-dione (6), and 1,7-diphenyl-1,6-heptadiene-3,5-dione (7), and evaluated their antioxidative activity. The in vitro oxidative damage to both lipids and proteins in rat liver mitochondria was used as a model to study the free radical-induced oxidative damage of biological lipids as well as proteins and the protective effects of these curcumin analogues. It was found that these compounds, except 6 and 7, could effectively inhibit the free radical induced lipid peroxidation and protein oxidative damage of rat liver mitochondria by H-atom abstraction from the phenolic groups. Compound 2 which bear ortho-diphenoxyl functionality exhibited remarkably higher antioxidative activity for lipids and proteins than curcumin and other analogues, and the 4-hydroxy-3-methoxyphenyl group also play an important role in the antioxidative activity.     

Synthesis of 3'-thioamido-modified 3'-deoxythymidine-5'-triphosphates and their use as chain terminators in Sanger-DNA sequencing

The thioamide derivatives 3'-deoxy-5'-O-(4,4'-dimethoxytrityl)-3'-[(2-methyl-1-thioxo- propyl)amino]thymidine 1 and 3'-deoxy-5'-O-(4,4'-dimethoxytrityl)-3'-((6-([(9H-(fluo-ren-9- ylmethoxy)carbonyl]-amino)-1-thioxohexyl)amino) thymidine 2 were synthesized by regioselective thionation of their corresponding amides 7 and 8 with 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (Lawesson's reagent). The thioamides were converted into the corresponding 5'-triphosphates 3 and 4. Compound 3 was chosen for DNA sequencing experiments and 4 was further labelled with fluorescein.     

Concise syntheses of arabinogalactans with beta-(1-->6)-linked galactopyranose backbones and alpha-(1-->3)- and alpha-(1-->2)-linked arabinofuranose side chains

4-methoxyphenyl glycosides of 2,3'-bis-alpha-L-arabinofuranosyl branched beta-D-(1-->6)-linked galactopyranosyl tetraose (16), 3',2'-bis-alpha-L-arabinofuranosyl branched beta-D-(1-->6)-linked galactopyranosyl hexaose (27), and a twentyose (42) consisting of beta-(1-->6)-linked D-galactopyranosyl pentadecaoligosaccharide backbone with alpha-L-arabinofuranosyl side chains alternately attached at C-2 and C-3 of the middle galactose residue of each consecutive beta-(1-->6)-linked galactotriose unit of the backbone, were synthesized with isopropyl 3-O-allyl-2,4-di-O-benzoyl-1-thio-beta-D-galactopyranoside (6), 2,3,4,6-tetra-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (7), 2,3,5-tri-O-benzoyl-alpha-L-arabinofuranosyl trichloroacetimidate (12), 6-O-acetyl-2,3,4-tri-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (17), 4-methoxyphenyl 2,3,4-tri-O-benzoyl-beta-D-galactopyranoside (19), and 2,6-di-O-acetyl-3,4-di-O-benzoyl-alpha-D-galactopyranosyl trichloroacetimidate (28) as the key synthons. Condensation of 6 with 7 gave the disaccharide donor 8, and subsequent condensation of 8 with 4-methoxyphenyl 2,3,4-tri-O-benzoyl-beta-D-galactopyranosyl-(1-->6)-2-O-acetyl-3,4-di-O-benzoyl-beta-D-galactopyranoside (9) followed by selective deacetylation afforded the tetrasaccharide acceptor 11. Coupling of 11 with 12 gave the pentasaccharide 13, its deallylation followed by coupling with 12, and debenzoylation gave the hexasaccharide 16 with beta-(1-->6)-linked galactopyranose backbone and 2- and 3'-linked alpha-L-arabinofuranose side chains. The octasaccharide 27 was similarly synthesized, while the twentyoside 42 was synthesized with tetrasaccharides 33 or 24 as the donors and 23, 36, 38, and 40 as the acceptors by consecutive couplings followed by deacylation.     

A new synthesis of certain 7-(beta-D-ribofuranosyl) and 7-(2-deoxy-beta-D-ribofuranosyl) derivatives of 3-deazaguanine via the sodium salt glycosylation procedure.

A facile synthesis of 7-beta-D-ribofuranosyl-3-deazaguanine (1) and certain 8-substituted derivatives of 1 via the sodium salt glycosylation method has been developed. Glycosylation of the sodium salt of methyl 2-chloro(or methylthio)-4(5)-cyanomethylimidazole-5(4)-carboxylate (5 and 13b) with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide (6) gave exclusively methyl 2-chloro(or methylthio)-4-cyanomethyl-1-(2,3, 5-tri-O-benzoyl-beta-D-ribofuranosyl)imidazole-5-carboxylate (7 and 14a), respectively. Ammonolysis of 7 and 14a provided 6-amino-2-chloro(or methylthio)-3-beta-D-ribofuranosylimidazo-[4,5-c]pyridin-4(5H)-one (11 and 17), which on subsequent dehalogenation (or dethiation) gave 1. Similarly, reaction of the sodium salt of 5 and 13b with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofuranose (8), and ammonolysis of the glycosylated imidazole precursors (9 and 16) gave 6-amino-2-chloro(or methylthio)-3-(2-deoxy-beta-D-erythro-pentofuranosyl) imidazo[4,5-c]-pyridin-4(5H)-one (10a and 15), respectively. Dehalogenation of 10a or dethiation of 15 gave 2'-deoxy-7-beta-D-ribofuranosyl-3-deazaguanine (10b). This procedure provided a direct method of obtaining 10b without the contaminating 9-glycosyl isomer 4.     

New antitumoral agents I: In vitro anticancer activity and in vivo acute toxicity of synthetic 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one and derivatives

This paper describes a new method for the preparation of 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one 1 and its derivatives 2–5. This set of synthetic compounds exhibited high antitumoral activities regarding in vitro screening against several human tumor cell lines as lung carcinoma NCI-460, melanoma UACC-62, breast MCF-7, colon HT-29, renal 786-O, ovarian OVCAR-03 and ovarian expressing the resistance phenotype for adriamycin NCI-ADR/RES, prostate PC-3, and leukemia K-562. Compounds were also tested against murine tumor cell line B16F10 melanoma and lymphocytic leukemia L1210 as well as to their effect toward normal macrophages. Specific activity against colon cancer cells HT-29 was observed for all tested compounds and suggests further studies with models of colon cancer. Compounds 1, 2, and 4 showed significant cytotoxic activity with IC₅₀ values ?2.3 μM for all human cancer cell lines. Intraperitoneal acute administration of compound 1 and 2 showed very low toxicity rate.