Synthesis and antiviral evaluation of 2′,2′,3′,3′-tetrafluoro nucleoside analogs

Herein, we report the synthesis of novel 2′,2′,3′,3′-tetrafluorinated nucleoside analogs along with their phosphoramidate prodrugs. A tetrafluoro ribose moiety was coupled with different Boc/benzoyl-protected nucleobases under Mitsunobu conditions. After deprotection, tetrafluorinated nucleosides 13b, 14b, 20b-22b were reacted with phenyl-(isopropoxy-l-alaninyl)-phosphorochloridate to afford corresponding monophosphate prodrugs 24b–28b. All synthesized compounds were evaluated against several DNA and RNA viruses including HIV, HBV, HCV, Ebola and Zika viruses.     

1,1′,2,2′,6,6′-Hexaphenyl-4,4′-bipyridinium cation radical

Aniline reacts with 2,2,6,6-tetraphenyl-4,4-bipyrilium perchlorate to form 1,1,2,2,6,6-hexaphenyl-4,4-bipyridine perchlorate. A relatively stable cation radical is formed in the first stage of electrochemical reduction of this compound, which has been examined by ESR, where there are splittings from two nitrogen nuclei and the four protons in the 3,3,5,5 positions: a_N=0.38; a_H=0.14 mT.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, No. 1, pp. 61–64, January–February 1992.     

Acclimation Response of Green Microalgae Chlorella Sorokiniana to 2,3′,4,4′,6-Pentachlorobiphenyl

The effect of the toxicant 2,3′,4,4′,6-pentachlorobiphenyl (PCB-119) on the growth, chlorophyll content, and PSII activity of C. sorokiniana cells was investigated. A strong negative effect of the toxicant was observed at PCB concentration of 0.05 μg mL⁻¹, when culture growth ceased, chlorophyll strongly bleached, and cell death occurred. The use of original highly sensitive fluorimeter to measure three types of high-resolution chlorophyll fluorescence kinetics allowed us to detect an initial dramatic decrease in the activity of primary photosynthetic reactions, followed by their almost complete recovery at the end of the incubation period when most cells were dead. The study of the distribution of individual cells in culture in terms of F_v/F_m parameter, which reflects the quantum yield of PSII photochemistry, revealed the existence of 2–3% of cells retaining high F_v/F_m (>0.7) in the presence of the toxicant. The treated cultures were able to resume growth after prolonged incubation in fresh medium. The high sensitivity fluorescence methods used made it possible to identify stress-resistant cells which maintain high photosynthetic activity in the presence of lethal doses of toxic substances; these cells provide recovery of the population after stress.     

Crystal structure of 1,1′-biphenyl-2,2′,3,3′-tetracarboxylic and 1,1′-biphenyl-2,2′,3,3′,5,5′,6,6′-octacarboxylic acids: solid-state chiralization and dissociation

X-ray diffraction analysis revealed unexpected stereochemical features accompanying crystal self-assembly of the two title oligocarboxylic acids.     

Synthesis and Taste Properties of 4,1′,4′,6′‐Tetrahalodeoxysucrose Analogues

The synthesis of a series of 1,4,6‐trideoxy‐1,4,6‐trihalo‐β‐d‐hexulofuranosyl 4‐deoxy‐4‐halo‐α‐d‐hexopyranosides is described. The 4‐chloro‐, 4‐bromo‐ and 4‐iodo‐4‐deoxy‐β‐d‐fructofuranosyl analogues were synthesized from a 3′,4′‐lyxo‐epoxide using the respective alkali metal halides. The corresponding 4‐halodeoxytagatofuranosyl analogues, on the other hand, were obtained by direct halide displacement of the 4′‐O‐trifluoromethanesulfonyl derivative, which was derived by regioselective sulfonylation of 1,6‐di‐O‐trityl‐β‐d‐fructofuranosyl 6‐O‐trityl‐α‐d‐glucopyranoside via its stannylene acetal. The sweetness intensities of these tetrahalodeoxy compounds strongly suggest that both size and configuration of the halogen substituents at C‐4 and C‐4′ are critical for sweetness enhancement.     

An Improved Synthesis of 2′-Hydroxy-3′,4′,6′-trimethoxyacylophenones

A wide variety of 2′-hydroxypolymethoxyacetophenones and propiophenones, e.g. 1a and 1b are used in the synthesis of flavone and ehromone natural products.¹ Repeated attempts to prepare 1a and 1b by reacting 1,2,3,5-tetramethoxybenzene 2 with acetyl or propionyl chlorides and AlCl₃ in ether² gave products which were difficult to purify.³ We traced the problem to ring-ethoxy contaminants which were isolated and tentatively identified as 3a and 3b.     

Synthesis of Steroidal Spiro-1′,2′,4′-triazolidine-3′-thiones

Steroidal ketone thiosemicarbazones (4–6), obtained from the corresponding ketones(1–3), on oxidative cyclization with H₂O₂ at 0°C provide title compounds (7–9), respectively. The structures of these compounds have been established on the basis of their elemental analytical and spectral data.     

LC Determination of trans-3,5,3′,4′,5′-Pentamethoxystilbene in Rat Plasma

A simple LC method has been developed and validated to determine trans-3,5,3′,4′,5′-pentamethoxystilbene (PMS) in rat plasma. Chromatographic separation was achieved through gradient delivery of acetonitrile and water (1.5 mL min^?1) at 50 °C. PMS was quantified using UV detection at 320 nm. The standard curve ranged from 15 to 1,500 ng mL^?1. The intra- and inter-day precisions, in terms of CV, were all less than 10% while the inter-day and intra-day bias ranged from ?6.8 to 8.3%. The plasma PMS levels were monitored in Sprague-Dawley rats after drug administration. This simple LC method appears to be useful in the pharmacokinetic investigation of PMS.     

Synthesis of 3,4-Biheterylthieno[2,3-b]-thiophenes. Part I: Synthesis of 3,4-Bi(1′,3′,4′-thiadiazolyl-, s-triazolyl-,1′,3′,4′-thiadiazinyl-, 1′,3′,4′-triazinyl-, thiazolyl-, 1′,3′-thiazinyl- and primidinyl)-thieno[2,3-b]thiophenes

3,4-Diamino-2,5-dicarbethoxythieno[2,3-b]thiophene ( 1 ) was allowed to react with NaNO 2 and active methylenes to afford the corresponding azo compounds 2a-c . Hydrazonyl chloride 2a was treated with carbon disulfide, phenyl isothiocyanate, benzonitrile, benzyl cyanide, malononitrile, benzalaniline, ethyl mercaptoacetate, and ethyl glycinate to give 1,3,4-thiadiazolyl-, s-triazolyl-, 1,3,4-thiadiazinyl-, 1,3,4-triazinylthieno[2,3-b]thiophenes 3-6 respectively. The reaction of 2b,c with urea, thiourea, and guanidine afforded pyrimidinyl- and thiazinylazothieno [2,3-b]thiophenes 7-10 respectively. Bithiazolylthieno[2,3-b]thiophenes 11 and 13 were synthesized by treating compound 1 with CS 2 along with halo compounds. The addition of S,S-, N,S-, and N,O-acetals to the Schiff base 14 afforded compounds 15-17 respectively.     

Synthesis and mesomorphic properties of 4-methoxyphenyl 4′- n -alkoxy-2′,3′,5′,6′-tetrafluorobiphenyl-1-carboxylates

A novel type of 4-methoxyphenyl 4′-n-alkoxy-2′,3′,5′,6′-tetrafluorobiphenyl-1-carboxylates have been synthesized. Textural observations by polarizing microscopy and DSC measurements of the phase transitions show that all of these compounds are thermotropic liquid crystals with only a nematic mesophase. The relationship between the properties and chemical structures of these compounds is discussed.     

Synthesis of Novel 1-Arylsulfonyl-4-(1′-N-2′, 3′, 4′, 6′-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazides

Some 1-arylsulfonylthiosemicarbazides have been reported as fungicides1 and bacterio-static agents2. Recently, it is well documented that thiosemicarbazide is a novel class ofnon-peptide antagonists for bradykinin B2 , which is beneficial in the symptomat…     

Synthesis of 1,3,1′,5′,6′,7′-hexahydro-3,3′-biindolyl-2,4′-dione derivatives by cyclization of 3-alkylideneoxindoles with enaminone

The reaction between 3-alkylideneoxindoles 1 and 3-aminocyclohex-2-enone 2 was studied, and an efficient synthesis of 1,3,1′,5′,6′,7′-hexahydro-3,3′-biindolyl-2,4′-dione derivatives was developed by a sequential Michael addition followed by intramolecular condensation catalyzed by nickel dichloride hexahydrate. The reaction mechanism is discussed.     

MASS SPECTROMETERY OF THE ISOMERIC OCTAHYDROBENZOPYRIMIDINE-2′-THIONE-4′,1-SPIROCYCLOHEXANE AND 2′-AMINOOCTAHYDROBENZO-3′,1′-THIAZINE-4′,1-SPIROCYCLOHEXANE

Abstract

Some authors have shown that tetrahydropyrimidine-2-thiones are hydrated in acidic solution and then isomerise to the 2-imino-or 2-enamino-1,3-thiazine.     

5′,5′,6,6-Tetramethyl-6,7-dihydro-3′H-spiro[1,3-benzodithiole-2,1′-cyclohexane]-3′,4(5H)-dione

Russian Journal of Organic Chemistry -     

Synthesis and Biological Activity of Novel 2,3-Dihydro-2-phenylsulfonylhydrazono-3-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyl)thiazoles

A series of novel 2,3-dihydro-2-phenylsulfonylhydrazono-3-(2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl) thiazoles were designed and synthesized via the reaction of thiosemicarbazide with chloroaldehyde.Their chemical structures were characterized by 1H and 13C NMR spectroscopy and elemental analysis.The bioassay results indicate that some of these compounds exhibit moderate fungicidal and herbicidal activities.     

Deoxyribonucleoside Cyclic 3′,5′-Phosphorofluondates

Abstract

The synthesis of nucleoside cyclic 3′,5′-phosphorofluoridates, so far not described compounds in the chemical literature, have been performed. As a key substrate we used 2′-deoxyribonucleoside cyclic 3′,5′-phosphorothioates (1) which have been obtained in this Laboratory several years ago.1     

Antioxidant Study and Assignments of NMR Spectral Data for 3′,4′,7-Trihydroxyflavanone 3′,7-Di-O-β-D-glucopyranoside (Butrin) and Its Hydrolyzed Product

The NMR spectral data including high resolution ¹H, ¹³C and 2D NMR for butrin, 3,4,7-trihydroxyflavanone 3,7-di-O--D-glucopyranoside, isolated from flowers of Butea monosperma, are reported here for the first time. Butrin was hydrolyzed using b-glucosidase to butin in high yield. They were subjected to free radical scavenging test using 2,2-diphenyl-1-picrylhydrazyl (DPPH) spectrophotometric assay. At a dose of 4 × 10^-8 mol of tested compounds, the percentage of reduced DPPH for butin was 14.5% while no reduction was observed for butrin (0%).     

Colorimetric Cyanide Chemosensor Based on 1′,3,3′,4-Tetrahydrospiro[chromene-2,2′-indole]

A new class of chemosensors based on the 1′,3,3′,4-tetrahydrospiro[chromene-2,2′-indole] ring system, which detects cyanide with high specificity, is described. These chemosensors show a distinct color change when treated with cyanide in acetonitrile solution buffered with sodium phosphate, and this procedure is not affected by the presence of other common anions. The chemisensors exhibit high sensitivity to low concentrations of cyanide, meeting the European Union water quality control criterion of sensitivity below 0.05 mg L⁻¹, and show a very fast response within tens of seconds. The mechanism for detection is rationalized by the nucleophilic substitution of the phenolic oxygen atom at the indoline C-2 atom by the cyanide anion to form a stable indolylnitrile adduct and to generate the colored 4-nitrophenolate chromophore. These chemosensors can be synthesized by a simple procedure from commercially available starting materials.     

Crystal structure of 4,4″-dinitro-[3,3′,4′,3″]-tris-[1,2,5]-oxadiazole

The crystal structure of a new energetic compound of 4,4″-dinitro-[3,3′:4,3″]-tris-[1,2,5]-oxadiazole is studied.