Tosyl Derivatives Research Articles

Synthesis and biological evaluation of 5-(alkyn-1-yl)-1-(p-toluenesulfonyl)uracil derivatives

Sonogashira coupling of 5-iodouracil (2) and trimethylsilylacetylene gave 5-(trimethylsilylethynyl)uracil (3), which was deprotected to give 5-ethynyluracil (4). Copper(I)-catalyzed cyclization of 4 gave furo[2,3-d]pyrimidin-2(3H)-one (5). Tosylation of 2 and 4 gave the 1-(p-toluenesulfonyl) derivatives 6 and 7, respectively. The tosylated compound 6 and trimethylsilylacetylene did not undergo Sonogashira coupling, and copper(I)-catalyzed cyclization of 7 did not occur. Coupling of 2 with several terminal alkynes gave 5-(alkyn-1-yl)uracil derivatives (9), which underwent tosylation to produce the targeted 5-(alkyn-1-yl)-1-(p-toluenesulfonyl)uracil compounds (11). Copper(I)-catalyzed cyclization of 9 gave the respective furopyrimidines (10) in low yields. Again, cyclization did not occur with the tosyl derivatives (11). Activity against varicella-zoster virus (VZV) was observed with longer-chain analogues of 9 and 11, and compound 7 showed activity against human cytomegalovirus (HCMV) at near cytotoxic levels.Key words: antiviral screening, furo[2,3-d]pyrimidin-2(3H)-one derivatives, Sonogashira coupling, 1-(p-toluenesulfonyl)pyrimidine derivatives.

Click Chemistry with Polysaccharides

AbstractSummary: The copper‐catalyzed Huisgen reaction as a typical example of click chemistry was realized with the polysaccharide cellulose for the first time. The generality, selectivity, and the efficiency of click chemistry perfectly fit the requirements of polysaccharide modification, which is demonstrated by the introduction of triazole‐spacer bound functional groups, i.e., carboxylic ester, thiophene, and aniline moieties. Azide moieties introduced into cellulose via the tosyl derivative were simply transferred with ethynyl compounds under Cu(I) catalysis and mild and easily applicable conditions. Hydrolytically stable cellulose derivatives soluble in organic solvents, e.g., DMSO or DMF with DS up to 0.9 are obtained. The triazole substituted cellulose derivatives were characterized by elemental analysis, FTIR, 1H NMR, and 13C NMR spectroscopies and show no impurities or substructures resulting from side reactions.6‐Azido‐6‐deoxy cellulose.magnified image6‐Azido‐6‐deoxy cellulose.

Synthesis and Characterization of Chiral [3,22]‐Ionenes

AbstractSummary: Two [3,22]‐ionenes with pendent chiral groups, glucopyranosyl‐[3,22]‐ionene and β‐cyclodextrin‐[3,22]‐ionene, were synthesized by the reaction between the tosyl derivatives of the carbohydrate (methyl alpha‐glucopyranoside or beta‐cyclodextrin) and the tertiary [3,22]‐polyamine obtained by selective demethylation of [3,22]‐ionene. The derivatives were characterized by 1H NMR spectroscopy, presenting degrees of substitution of 30 and 45% for the glucosyl and cyclodextrin derivatives, respectively. It was shown by using pyrene as the fluorescent probe, that both polymers form hydrophobic domains, characteristic of micelle‐mimetic polysoaps in aqueous solution.

Substituted Pyrrolo[3,4-a]carbazoles from Reactions between 3-(1-Methoxy-vinyl)indoles and Maleimides

5-Methylenolether derivatives of pyrrolo[3,4-a]carbazoles were obtained from cycloadditions between 3-(1-methoxyvinyl)-1-tosylindole and N-substituted maleimides. They were transformed into the hydroxy derivatives by treatment with H2SO4, selectively reduced to the ether by H2/Pd–C, and in the imide moiety by L-Selectride®. From the analogous BOC protected indole derivative the parent α,β-unsaturated ketones were obtained, which were transformed into hydroxyimino compounds, and which could be deprotected by heating to the melting point. Deprotection of the tosyl derivatives was not successful. The imide part of the molecule was hydrolyzed using methanolic NaOH. The stereochemistry of all products was elucidated mainly by spectroscopic methods, and compared with results of calculations.

New pyrano[3,4- b]indoles from 2-hydroxymethylindole and l-dehydroascorbic acid

2-Hydroxymethylindole reacts with l-dehydroascorbic acid under mild conditions to give (3 R,3a R,10c S)-3-[(1 S)-1,2-dihydroxyethyl]-3a,10c-dihydroxy-3a,5,6,10c-tetrahydrofuro[3′,4′:5,6]pyrano[3,4- b]indol-1(3 H)-one. Its tosyl derivative undergoes cyclization to form a pentacyclic ketal derivative.

Synthesis of oligo-6-bromo-6-deoxy-β-cyclodextrins

Two methods of synthesis of oligo-6-bromo-6-deoxy-β-cyclodextrins, with use of the Vilsmeier-Haack reagent and via tosyl derivatives of β-cyclodextrin, were compared. The second method holds more promise, since it allows a desired number of bromine atoms to be introduced into the β-cyclodextrin molecule instead of hydroxy groups. A correlation between the decomposition onset points of oligo-6-bromo-6-deoxy-β-cyclodextrins and the number of bromine substituents in them was revealed.

Synthesis of 3α,12α-dihydroxy-23a, 23b-dihomo-5β-cholan-24-oic acid

A novel multi-step synthesis of 3α,12α-dihydroxy-23a,23b-dihomo-5β-cholan-24-oic acid (23a,23b-dihomodeoxycholic acid) (5) has been achieved from methyl 3α,12α-dihydroxy-5β-cholanoate (1). Reduction of compound 1 with LiAlH 4 in dry ether gave the corresponding alcohol 2 in 83 % yield. Selective esterification of compound 2 with tosyl chloride in dry piridine at 0-5 °C for 12 h afforded the 3α,12α-dihydroxy-5β-24-cholanyl tosylate (3) in 64 % yield. The reaction of the tosyl derivative 3 with sodium diethyl malonate gave compound 4 which was first subjected to hydrolysis under basic conditions, followed by decarboxylation under acidic conditions to afford 3α,12α-dihydroxy-5β-23a,23b-dihomocholan-24-oic acid in 84 % yield.

Tosylation of Endocrine-Disruptive Alkylphenolic Compounds in a Solid-Phase Reaction System Consisting of C18-Modified Silica Gel and Aqueous Buffer Solution

The tosylation reaction of endocrine-disruptive alkylphenolic compounds in a solid-phase aqueous system was investigated with the aim of developing an environment-friendly and efficient derivatization method for HPLC analyses of environmental samples. The phenols were rapidly and efficiently converted to the tosyl derivatives on a commercially available ODS solid-phase cartridge by passing an aqueous buffer solution through it. The solid-phase aqueous tosylation system has been incorporated into a preconcentration step performed by solid-phase extraction from environmental water.

Syntheses of disaccharide- and nucleoside-substituted cyclopentadienyl and indenyl ligands

This paper describes syntheses of new chiral cyclopentadienes and indenes derived from a disaccharide (trehalose) and a nucleoside (uridine). The reaction of lithium cyclopentadienide and indenide with a disaccharide, derived from trehalose, bearing methylated secondary hydroxyls and primary triflate groups, affords the trehalose bis-cyclopentadiene ( 5) and the trehalose bis-indene ( 6).These compounds have been fully characterized by NMR spectroscopy and the molecular structure of the trehalose bis-indene has been determined by X-ray diffraction. From uridine, a nucleoside in which secondary hydroxyls have been protected with isopropylidene groups and the free primary hydroxyl function transformed into the tosylate derivative, the reaction with lithium cyclopentadienide or lithium indenide under sonication conditions leads to either uridine cyclopentadiene ( 9) or uridine indene ( 10). The molybdenum(II) complex 7 has been obtained from trehalose bis-cyclopentadiene and its molecular structure determined by X-ray diffraction. From the uridine cyclopentadiene the molybdenum(II) complex 11 has been prepared and characterized.

A novel probe for imaging amyloid‐β: Synthesis of F‐18 labelled BF‐108, an Acridine Orange analog

AbstractThe synthesis of 3‐(2‐[18F]fluoroethyl)ethylamino‐6‐diethylaminoacridine ([18F]BF‐108), a potential positron‐labelled probe for imaging amyloid‐β is described. The precursor tosylate derivative was fluorinated with [18F]KF/ Kryptofix 222 in acetonitrile, and the crude product was purified by semi‐preparative HPLC to give the radiolabelled BF‐108. The radiochemical purity was >95% and the maximum specific activity was 33.9 TBq/mmol at the end of the synthesis (EOS). The synthesis time was 130 min from the end of bombardment (EOB). Copyright © 2003 John Wiley & Sons, Ltd.

Ionic conductivity of poly[N-(3,6,9-trioxadecyl)-4-vinylpyridinium)] salts with univalent counter-ions in aqueous solutions

In order to determine the counter-anion effect on conductivity of poly[N-(3,6,9-trioxadecyl)-4-vinylpyridinium)] backbone in aqueous solutions, a set of three polyelectrolytes with three different counter-ions: poly[N-(3,6,9-trioxadecyl)-4-vinylpyridinium]bromide P4VP164Br and its chlorate and tosylate derivatives P4VP164ClO 4 and P4VP164Ts respectively, were prepared by spontaneous polymerization of 4-vinylpyridine. This method gives a grafted polyelectrolyte having a positive charge on each pyridinic moiety on the backbone. The conductivities of cationic polyelectrolyte aqueous solution were determined in the concentration range from 10 −4 to 10 −2 M at 25 °C. The variation of the conductivity versus concentration of the investigated system exhibits a typical polyelectrolyte behavior. The polycation mobility was found to be dependent on the counter-anion nature. Thus, the polyelectrolyte conductivity increases with the ion size. This shows that big ions are weakly or not associated to the backbone. In order to confirm this steric hindrance, we have considered the conductivities of these three anions Br −, ClO 4 − and Ts − in their sodium salts, both alone and in the presence of 3,6,9-trioxadecanol (PEO164) free chains. In the two cases, the conductivities decrease in the order Λ Br> Λ ClO 4 > Λ Ts. These results suggest that counter-ion mobility is mainly influenced by steric effect PEO164 grafted chains. Values of the conductivity predicted from Manning rod-like polyelectrolyte model were compared with our experimental results.

The preparation of thiophene-based azacryptand Mannich bases

The preparation of cryptand-like structures, incorporating four thiophene rings, was undertaken. A variety of approaches were considered, but a stepwise process commencing from the readily available α,ω-bis(2-formyl-3-thienyloxy)alkanes of the type ArO-Z-OAr (where Ar = 2-formyl-3-thienyl and Z = heteroalkyl chain) yielded excellent results. A range of open chain and cyclic Mannich bases incorporating one or two macrorings was prepared via reduction of open chain and macrocyclic imines derived from the heteroalkyl-bridged bisaldehydes. Tosyl and acetyl derivatives of the reduced products, viz. the intermediate secondary amines were prepared; the latter exhibited diastereoisomerism.

Acidobasic equilibria and spectral characteristics of acetyl and tosyl derivatives of 4,4′-diaminostilbene-2,2′-disulfonic acid

Acetyl and tosyl derivatives of 4,4′-diaminostilbene-2,2′-disulfonic acid and their N, N′-dimethyl analogues were prepared. The course of syntheses was checked by HPLC and products were identified with NMR spectroscopy. Chemical stability was tested in phosphate buffers. Acidobasic properties of prepared substances were studied with potentiometric titration and also with absorption and fluorescence spectrophotometry. The fluorescence quantum yields of pure acidobasic forms were measured. The tosylamino derivative was found to behave as N-acid and in aqueous alkali medium exhibits a strong fluorescence. The p K A values were estimated.

Preparation of a d-Glucose-Derived Alkene. An E2 Reaction for the Undergraduate Organic Chemistry Laboratory

As the carbohydrates continue to gain attention for their central role in numerous areas of chemistry and biology, there is a growing need for experiments at the undergraduate level that highlight these fascinating compounds. In this article we describe a simple two-step laboratory experiment that may be used to highlight several important concepts introduced in sophomore organic chemistry, as applied to compounds of potential biological interest. The sequence begins with commercially available diacetone glucose, which is converted to the highly crystalline tosylate derivative. Upon treatment of compound 2 with potassium tert-butoxide in THF solution, the alkene (3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-erythro-hex-3-enofuranose) is formed via an E2 reaction. The synthetic sequence allows for discussion of various concepts within organic chemistry, as well as for the application of analytical techniques such as polarimetry and one- and two-dimensional NMR.

Tosylates in palladium-catalysed coupling reactions. Application to the synthesis of arylcoumarin inhibitors of gyrase B

The palladium-catalysed coupling reaction between tosylate derivatives and organostannanes has been investigated as a methodology for carbon–carbon bond formation. Aryl substituents have been successfully incorporated even in highly functionalised coumarin structures to afford new analogues of the antibiotic novobiocin.

Stereostructure, conformation and reactivity of P- and a-gardiol from Burchellia bubalina

Abstract From the leaves of Burchellia bubalina (Rubiaceae) pure P- and a-gardiol have been isolated, the latter in crystalline form for the first time. X-ray analysis of P-gardiol establishes its relative configuration. Treatment of the tosyl derivative of P-gardiol with base affords a crystalline elimination product amenable to X-ray analysis. Evidence is presented for the partial conversion of a-gardiol to the epimeric P-gardiol at room temperature. Molecular dynamic studies at 1000 K on the two gardiols provide useful conformational information. In the case of P-gardiol, the analysis shows interesting correlations between conformations adopted at 1000 K and those present in the crystalline state at room temperature.

Synthesis of 2,3-Disubstituted Indoles via Palladium-Catalyzed Annulation of Internal Alkynes

The palladium-catalyzed coupling of 2-iodoaniline and the corresponding N-methyl, -acetyl, and -tosyl derivatives with a wide variety of internal alkynes provides 2,3-disubstituted indoles in good-to-excellent yields. The best results are obtained by employing an excess of the alkyne and a sodium or potassium acetate or carbonate base plus 1 equiv of either LiCl or n-Bu4NCl, occasionally adding 5 mol % PPh3. The yields with LiCl appear to be higher and more reproducible than those obtained with n-Bu4NCl. The process is quite general as far as the types of substituents which can be accommodated on the nitrogen of the aniline and the two ends of the alkyne triple bond. The reaction is quite regioselective, placing the aryl group of the aniline on the less sterically hindered end of the triple bond and the nitrogen moiety on the more sterically hindered end. This methodology readily affords 2-silylindoles, which can be easily protodesilylated, halogenated, or reacted with alkenes and Pd(OAc)2 to produce 3-substituted indoles, 2-haloindoles, or 2-(1-alkenyl)indoles, respectively. The presence of alcohol groups in the alkyne seems to have a particularly strong directing effect, perhaps due to coordination with palladium. This catalytic process apparently involves arylpalladium formation, regioselective addition to the C−C triple bond of the alkyne, and subsequent intramolecular palladium displacement.

Regiochemistry of the reductive Heck coupling of 2-azabicyclo[2.2.1]hept-5-ene. Synthesis of epibatidine analogues

The Diels-Alder adduct between cyclopentadiene and the iminium salt of formaldehyde was coupled as its boc-derivative with two aryl iodides. The coupling takes place in a regiospecific manner giving the corresponding 5-aryl-2-azabicyclo[2.2.1]heptane derivatives. The structure of the tosyl derivative 8 was established by X-ray analysis.

Synthesis and Structural Characterization of 5-Bromo-2,3-dimethylphenol

Bromination of the disubstituted 4,5-dimethyl-1,3-cyclohexanedione (6) followed by oxidation of the resulting 3-bromo-5,6-dimethyl-2-cyclohexen-1-ones (7) gave 5-bromo-2,3-dimethylphenol (1) together with its constitutional isomer 3. The structure of 1 was secured by a x-ray analysis of its tosyl derivative 8.

Transformações químicas do (+)-10b,14-diol-allo-aromadendrano, isolado de duguetia glabriuscula r. e. fries (r. e. fries) (annonaceae) e avaliações biológicas de alguns derivados obtidos

The sesquiterpene (+)-allo-aromadendrane-10b-14-diol 1 was the lead compound to the preparation of several derivatives in order to test their biological activity against A. salina, C. sphaerospermum, E. coli and S. aureus. In this way the monoalcohols (+)-viridiflorol 4, 9 and 11 were synthesized from 1 together with the acetal 6, the ketal 7, and the ketone 8. The oxirane 3 and nitrile 5 were also prepared using as an intermediate the tosylate derivative 2.