Synthesis and antiviral activities of some 4,4'- and 2,2'-dihydroxytriphenylmethanes

We synthesized some 4,4'- and 2,2'-dihydroxytriphenylmethane derivatives 3a--e and 4a--c by condensation of phenol 1 and aromatic aldehyde 2 in moderate to good yields (30--83%). Most of them showed significant antiviral activity against herpes simplex virus type 1 (anti-HSV-1 activity) in a plaque reduction assay. The most potent antiviral activity (EC(50)=0.79 microg/ml) was observed in the 4,4'-dihydroxytriphenylmethane derivative 3b. This compound 3b showed lower cytotoxicity (CC(50)=30.2 microg/ml), compared to that of the prototype 3a.     

Synthesis of 2,2'-dihydroxybisphenols and antiviral activity of some bisphenol derivatives

New diphenylmethane-type 2,2'-dihydroxybisphenols (5a-d) were prepared regioselectively in good yields. We evaluated the antiviral activity of some bisphenol derivatives synthesized by the plaque reduction assay. Most of the compounds showed significant antiviral activity and the 4,4'-dihydroxybisphenol derivative (10) showed higher activity than 2,2'-bisphenol derivatives. This compound had EC50 value of 1.8 microg/ml.     

Cyclization of 1-(4,4-diethoxybutyl)-3-aryl(thio)ureas to 2-arylpyrrolidines and 2,3´-bipyrrole derivatives

A reaction of 1-(4,4-diethoxybutyl)-3-phenylthiourea with resorcinol, 2-methylresorcinol, pyrogallol, and hydroquinone in chloroform in the presence of trifluoroacetic acid leads to 2-aryl-1-(N-phenylcarbamothioyl)pyrrolidines. 1-(4,4-Diethoxybutyl)-3-arylureas and 1-(4,4diethoxybutyl)-3-arylthioureas in the presence of an acid catalyst undergo intramolecular cyclization and dimerization with the formation of 1,1´-bis(N-arylcarbamo(thio)yl)-2,3´-bipyrrole derivatives.     

Synthesis and biological studies of some new acrylic acid ethyl esters of quinolinone

Abstract  

A series of new acrylic acid ethyl esters of quinolinones were synthesized from 4-(bromomethyl)quinolinones and screened for in vitro antimicrobial and in vivo analgesic and anti-inflammatory activities. Most of the compounds with chloro substitution at the C-6 or C-7 position in the quinolinone moiety and a methoxy group in the aryloxy moiety showed potent antibacterial and antifungal activities when compared with non-halogenated quinolinones and the quinolinones bearing a CH₃ at the C-8 position. In a pharmacological evaluation, the halogen substitution at the C-6 or C-7 position in quinolinones was found to enhance both analgesic and anti-inflammatory activities of the molecule when compared with a simple unsubstituted (non-halogenated) quinolinone. The structures of all newly synthesized compounds were characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR, and FAB-MS.     

5-Alkynyl-2′-deoxyuridines, containing bulky aryl groups: evaluation of structure-anti-HSV-1 activity relationship

Four 5-alkynyl-2′-deoxyuridines containing different bulky substituents and flexible linkers between the triple bond and the aromatic residue have been prepared and tested against HSV-1 in Vero cells. Two nucleosides containing carbonyl groups, 5-(4-benzoylphenoxypropyn-1-yl)-2′-deoxyuridine (19a) and 5-(estron-3-yloxypropyn-1-yl)-2′-deoxyuridine (19c), showed low cytotoxicity and moderate antiviral activity. The flexible linker appears not to be favorable for antiviral properties of 5-alkynyl-2′deoxyuridines: 5-[(perylen-3-yl)methoxypropyn-1-yl]-2′-deoxyuridine (19d) showed considerable cytotoxicity and no antiviral activity in contrast to the active and nontoxic 5-(perylen-3-ylethynyl)-2′-deoxyuridine (9), a nucleoside with a rigid triple-bond-connection of the aromatic system to the nucleobase.     

Acyclic analogs of nucleosides. Synthesis and in vitro antiviral activity of hydroxyalkyl-2-(trifluoromethylthiomethyl) benzimidazoles

In a search for novel antiviral compounds of the doubly modified nucleoside type, we have prepared 1-(4-hydroxy-2-oxabutyl)-, 1-(4-hydroxy-3-hydroxymethyl-2-oxabutyl)-, 1-(4-hydroxy-1-hydroxymethy1-2-oxabutyl)-, 1-(4-hydroxy-1-methyl-2-oxabutyl), 1-(4,5-dihydroxy-2-oxapentyl)-, 1-(5-hydroxy-2-oxapentyl), 1-(5-hydroxy-1-chloromethyl-2-oxapentyl)-, and 1-(6-hydroxy-1-chloromethyl-2-oxahexyl)-2-(trifluoromethylthiomethyl)benzimidazole. They were obtained by condensing the trimethylsilyl derivative of 2-(trifluoromethylthiomethyl) benzimidazole with alkylating agents in the presence of an equimolar mixture of trifluoromethanesulfonic acid and trimethylchlorosilane. These nucleoside analogs showed moderate antiviral activity against some RNA viruses.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 493–496, April, 1989.     

The coloring constituents of Scleroderma sinnamariense (Sclerodermaceae)

Two known coloring constituents, methyl 4,4'-dimethoxyvulpinate (1) and 4,4'-dimethoxyvulpinic acid (2) have been isolated from the fruit body of fungus Scleroderma sinnamariense Mont. The methanolic extract, its fractions and compound (2) showed moderate activity to inhibit the growth of some pathogenic testing microbes used.     

Synthesis and biological evaluation of novel tert-azido or tert-amino substituted penciclovir analogs

tert-Azido or amino substituted penciclovir analogs, 1-3 were synthesized for the purpose of improving the efficacy and bioavailability of penciclovir and searching for novel antiviral agents. Among several methods attempted to insert an azido group into the alpha,beta-unsaturated ester 6, only Bronsted acid-catalysed 1,4-conjugate addition conditions (NaN3, 75% acetic acid, 80 degrees C) gave the desired tert-azido product 7. The synthesized final penciclovir analogs 1-3 were evaluated in vitro against several viruses such as HIV-1, HSV-1 and 2, poliovirus, VZV, and VSV. Compound 2 only showed weak antiviral activity against HSV-1 without cytotoxicity. Although the synthesized compounds did not exhibit an excellent antiviral activity, the successful method used in introducing the tert-azido group is expected to be generally utilized for the synthesis of nucleoside analogs with a tert-azido substituent.     

Synthesis and antiviral activities of N-mono- and/or N,N'-di-carbamoyl and acyl derivatives of symmetrical diamines

N-carbamoyl and N-acyl diamine derivatives were synthesized from symmetrical diamines by their addition to iso(thio)cyanates, cleavage reaction of acid anhydride, or N-acylation by acyl chloride. (1R,2R)-1,2-Diaminocyclohexane [(1R,2R)-1], meso-1,2-diaminocyclohexane (meso-1), (1R,2R)-1,2-diphenylethylenediamine [(1R,2R)-3], or meso-1,2-diphenylethylenediamine (meso-3) were used as the starting symmetrical diamines. The target compounds synthesized herein were evaluated for antiviral activity with herpes simplex virus type 1 (HSV-1). A few derivatives of 1,2-diaminocyclohexane [(1R,2R)-7aa and cis-7b] with adamantyl group(s) showed significant antiviral activity (EC(50)=16.0, 27.0 microg/ml).     

Six new metal-organic frameworks with multi-carboxylic acids and imidazole-based spacers: syntheses, structures and properties

Six new metal-organic frameworks [Cu(obba)(bimb)·(obbaH(2))](n) (1), [Cu(obba)(bimb)](n) (2), [Zn(2)(obba)(2)(bimb)(2)(DMF)(2)(H(2)O)(3.5)](n) (3), [Ni(3)(2,2',4,4'-bptcH)(2)(bimb)(2)(H(2)O)(2)·(H(2)O)(2)](n) (4), [Ni(2)(bimb)(3)(H(2)O)(6)·(aobtc)·(DMF)(2)·(H(2)O)(2)](n) (5) and [Cd(3,3',4,4'-bptcH(2))(H(2)O)·(bimb)](n) (6), were obtained by reactions of 4,4'-bis(1-imidazolyl)biphenyl (bimb) and multi-carboxylic acids of 4,4'-oxybis(benzoic acid) (obbaH(2)), 2,2',4,4'-biphenyltetracarboxylate acid (2,2',4,4'-bptcH(4)), azoxybenzene-3,3',5,5'-tetracarboxylic acid (aobtcH(4)), and 3,3',4,4'-biphenyltetracarboxylate acid (3,3',4,4'-bptcH(4)) with corresponding metal salts under hydro/solvothermal conditions, respectively. Complexes 1-3 have entangled structures with different topologies: 1 is a 3-fold interpenetrating NbO three-dimensional (3D) network; 2 is a 3-fold interpenetrating dmp 3D net; 3 is a 6-fold interpenetrating dia 3D chiral net containing rare 1D helical chains with the same handedness. Complex 4 is an uninodal 6-connected network with a Sch?fli symbol of (4(8)6(4)8(3)) based on the trinuclear Ni(II) subunits, while complexes 5 and 6 are 1D chains. Interestingly, compound 6 represents the rare example of MOFs that exhibit high photocatalytic activity for dye degradation under visible light and shows good stability towards photocatalysis. Complexes 3 and 6 exhibit intense blue emissions in the solid state at room temperature whereas 3 appears to be a good candidate of novel hybrid inorganic-organic NLO material.     

修饰NADH模拟物的金属-有机三元环光催化制氢

将含有不同还原型烟酰烟腺嘌呤二核苷酸(NADH)活性中心模拟物的有机配体H₂L¹和H₂L²与钴离子配位自组装获得2例具有氧化还原活性且带有正电荷的金属-有机大环Co-L¹和Co-L²。选择阴离子型钌基光敏剂[Ru(dcbpy)₃]^4-(dcbpy=2,2′-联吡啶-4,4′-二羧酸)作为光敏中心,金属-有机大环结构作为质子还原催化剂,通过静电作用力将光敏中心封装在其空腔内部以加速光诱导电子转移(PET)过程,构建了人工光合成体系并应用于光解水制氢研究。相比于未修饰NADH模拟物的金属-有机大环Co-L³以及未修饰NADH模拟物但配位环境相同的单核催化剂Co-L⁴,由Co-L¹和Co-L²构建的金属-有机大环主客体超分子体系的光催化产氢效率分别提高1.6和6倍,可能是由于NADH活性中心模拟物的引入以及主客体超分子体系的形成有利于光敏中心与催化中心之间的光致电子转移过程。     

Preparation of 2,2'-dihydroxytriphenylmethanes using metal phenolates with aromatic aldehydes

The reactions of oxophilic metal phenolates having electron-donating substituents (1a-c) with aromatic aldehydes (2, 3) were selectively condensed at the ortho-position of the starting phenol to afford 2,2'-dihydroxytriphenylmethanes (8-11). This method was also applicable to the preparation of bisphenols (12-17) starting with naphthaldehydes (4, 5) and pyridinecarboxaldehydes (6, 7), but in low yields. In the case of these aldehydes (4-7), satisfactory yields could be obtained by sonication.     

阿魏酸酰腙类化合物的合成及生物活性

将酰腙结构引入到阿魏酸衍生物中,合成了6个阿魏酸酰腙类化合物,其结构经过了IR、~1H NMR、~(13)C NMR和ESI-HRMS表征。抗病毒活性测试结果表明,在质量浓度为500mg/L时,化合物3、5和6对烟草花叶病毒(TMV)在保护、治疗和钝化活性方面的抑制率均优于对照药剂病毒唑。进一步的EC_(50)测试结果表明,化合物3、5和6钝化活性的EC_(50)值分别为91.25、54.86、58.22mg/L,明显低于病毒唑的EC_(50)值(126.05mg/L)。该研究结果表明,阿魏酸酰腙类化合物对TMV具有较好的抗病毒活性,对其进行适当的结构改进和优化,有望得到具有更高抗病毒活性的化合物。     

Mixed-ligand oxovanadium complexes incorporating Schiff base ligands: synthesis, DNA interactions, and cytotoxicities

Three oxovanadium complexes, namely [VO(NOSAA)(bpy)] (1) (NOSAA = 2-hydroxy-5-nitrosalicylidene anthranilic acid, bpy = 2,2′-bipyridyl), [VO(NOSAA)(4,4′-dimebpy)] (2) (4,4′-dimebpy = 4,4′-dimethyl-2,2′- bipyridyl), and [VO(NOSAA)(phen)] (3) (phen = 1,10-phenanthroline), have been prepared and characterized. The binding modes and strengths of these complexes with calf thymus DNA (CT-DNA) were studied using various techniques. The chemical nuclease activities and photocleavage reactions of the complexes were also tested. All three complexes interact with CT-DNA through intercalative modes, and complex 3 possesses the largest binding affinity. All three complexes can efficiently cleave pBR322 DNA upon irradiation or under physiological conditions in the presence of H₂O₂, and complex 3 has the best cleaving ability. In vitro experimental results showed that the three complexes are cytotoxic against myeloma (Ag8.653) and gliomas (U251) cell lines and complex 3 again showed the highest efficacy.     

Synthetic Approaches to Physiologically Active Polycyclic Compounds: VI. Synthesis of 1-[(2<Emphasis Type="Italic">R</Emphasis>,3<Emphasis Type="Italic">S</Emphasis>)-<Emphasis Type="Italic">N</Emphasis>-Benzoyl-phenylisoseryloxy]-4,4-dimethyladamantane

A convenient procedure was proposed for the synthesis of 4,4-dimethyladamantan-1-ol from 2-adamantanone. Esterification of the product with protected amino acid gave 1-[(2R, 3S)-N-benzoylphenyl-isoseryloxy]-4,4-dimethyladamantane.     

Sodium and potassium benzeneazophosphonate complexes with crown ethers: Solid-state microwave synthesis, characterization and biological activity

The eco-friendly synthesis, spectroscopic (IR, MS, ¹H and ¹³C NMR) study and biological (cytostatic, antiviral) activity of sodium and potassium benzeneazophosphonate complexes, obtained by reaction in the solid state under microwave irradiation of the alkali salts of ethyl [α-(4-benzeneazoanilino)-N-benzyl]phosphonic acid and [α-(4-benzeneazoanilino)-N-4-methoxybenzyl]phosphonic acid with crown ethers containing 18-membered (dibenzo-18-crown-6 and bis(4′-di-tert-butylbenzo)-18-crown-6), 24-membered (dibenzo-24-crown-8) and 30-membered (dibenzo-30-crown-10) macrocyclic rings, have been described. The simple work-up solvent free reaction is an efficient green procedure for the formation of mononuclear crown ether complexes in which the sodium/potassium ion is bound to oxygen atoms of the macrocycle and the phosphonic acid oxygen. The free crown ethers, alkali benzeneazophosphonate salts and their complexes were evaluated for their cytostatic activity in vitro against murine leukemia L1210, murine mammary carcinoma FM3A and human T-lymphocyte CEM and MT-4 cell lines, as well as for their antiviral activity against a wide variety of DNA and RNA viruses. The investigated compounds showed no specific antiviral activity, whereas all the free crown ethers and their complexes demonstrated cytostatic activity, which was especially pronounced in the case of bis(4′-di-tert-butylbenzo)-18-crown-6 and its complexes.     

New triterpenoid saponins from the roots of Platycodon grandiflorum

Bioassay-directed fractionation of the antiviral active fraction of the roots of Platycodon grandiflorum leads to the isolation of three new triterpenoid saponins, platycosides G1-G3 (1-3), as well as two known saponins, platycodin D3 (4), and platycoside E (5). The structures of the new compounds were elucidated on the basis of their spectral data and chemical evidences. The isolated saponins were tested for their antiviral activities against respiratory syncytial virus (RSV), herpes simplex type 1 virus (HSV-1) and influenza type A virus (Flu A). Compound 4 showed weak anti-RSV activity.     

Carboxylic acid–pyridine supramolecular heterocatemer in a co-crystal

Robustness of carboxylic acid–pyridine supramolecular heterosynthon was examined in three 1:2 binary co-crystals of 4,4′-bipyridine with monocarboxylic acids, (4,4′-bipyridine)·(dl-hydroxyphenylacetic acid)₂, 1; (4,4′-bipyridine)_0.5·(4-bromonaphthalene-1-carboxylic acid), 2 and (4,4′-bipyridine)_0.5·(4-methylbenzoic acid), 3. All the three co-crystals form “two-component supermolecules” (consisting of one molecule of 4,4′-bipyridine and two molecules of the relevant carboxylic acid) stabilized through carboxylic acid–pyridine heterosynthons. Co-crystals 1 and 2 exhibits the expected carboxylic acid–pyridine dimer (heterodimer I) whereas co-crystal 3 forms a novel carboxylic acid–pyridine catemer (heterocatemer II).     

New Reactions of (2-Aminophenyl)diphenylmethanol with Carbonyl Compounds

Reactions of (2-aminophenyl)diphenylmethanol with ketones (dimedone, camphor, and 3-bromocamphor) in acetic acid result in the formation of arylimines of camphore and 3-bromocamphore, substituted tetrahydroacridin-1(2H)-one and 2-methyl-4,4-diphenylbenzoxazine.     

Syntheses,crystal structures,and properties of various one- dimensional coordination polymers based on macrocyclic metallic tectons and dicarboxylic acid ligand

The reaction of different macrocyclic metallic tectons and dicarboxylic acid ligand yielded six new coordination polymers, namely, {[(NiL¹)(4,4'-Bpdc)] ? DMF ? 2.5H₂O} _n (I), {[(NiL²)(4,4'-Bpdc)] ? DMF ? 2.5H₂O} _n (II), [(NiL³)₂(4,4'-Bpdc)_1.5][(NiL³)(4,4'-Bpdc)] ? ClO₄ ? 28H₂O (III), {[(NiL⁴)(4,4'-Bpdc)] ? 4H₂O} _n (IV), {[(NiL⁵)(4,4'-Tpdc)] ? 5H₂O} _n (V), {[(NiL³)(4,4'-Tpdc)]} _n (VI) (L¹ = 1,4,7,9,12,14-hexaaza-tricyclo[12.2.1.1^4.7]octadecane, L² = 1,3,10,12,15,18-hexaazatetracyclo[16.2.1.1^12.15.0^4.9]docosane, L³ = 11-methyl-1,4,8,10,13,15-hexaaza-tricyclo[13.3.1.1^4.8]icosane, L⁴ = 1,3,10,12,16,19-hexaazate-tracyclo[17.3.1.1.^12.16,0^4.9]tetracosane, L⁵ = 1,4,8,10,13,15-hexaaza-tricyclo[13.3.1.1^4.8]icosane, 4,4'-Bpdc = 4,4'-biphenyldicarboxylic acid and 4,4'-Tpdc = 4,4'-terphenyldicarboxylic acid) (CIF files CCDC nos. 1055545–1055550 for I–VI, respectively). Except for the different conformations of the macrocyclic metallic tectons or dicarboxylic acid ligands, complexes I–VI crystallized under the same environment, however, they exhibit diverse packing mode of infinite 1D coordination polymers, showing macrocyle or dicarboxylic acid ligand regulated self-assemble. The solid states UV-Vis for complexes I–VI also have been investigated.