Mercapto Derivatives Research Articles

Steroidal C-21 mercapto derivatives as dissociated steroids: Discovery of an inhaled dissociated steroid

A series of C-21 mercapto derivatives of hydrocortisone have been synthesized and evaluated in cell based transrepression and transactivation assays. The benzothiazole derivative, compound 6 not only showed a dissociated profile in vitro functional assays but also a pharmacological profile in a Brown-Norway rat therapeutic index model of asthma that dissociated side effects (thymolysis) while maintaining efficacy against pulmonary inflammation and lung function.

Synthesis, antitumor and antioxidant evaluation of some new thiazole and thiophene derivatives incorporated coumarin moiety

3-Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of 2-aminothiazole derivative 3 via bromination of 1 followed by treatment of the formed acetylbromide 2 with thiourea or via Bignailli reaction of 1. Treatment of 3 with 2 afforded the bis-coumarin 4, whereas, cyanoacetylation of 3 followed by treatment of the formed cyanoacetamide 6 with salicyaldehyde give the bis-coumarin 7. Reaction of 6 with phenyl isothiocyanate in DMF/KOH produced the potassium salt 8, which cyclized with chloroacetyl chloride to give the thiazolidinone 9. Acidification of 8 with HCl afforded the thiocarbamoyl 10, which condensed with 2 in DMF to give the mercapto derivative 12, whereas in DMF/TEA gave the thiophene derivative 13. The thiophenes 15a–c were achieved via treatment of the thiocarbamoyls 14a–c with 2 in DMF/TEA, whereas, in DMF gave the corresponding thiazoles 16a–c. Treatment of the components 17a, b with carbon disulfide in DMF/KOH followed by addition of 2 afforded the dithioacetals 19a, b. Cyclization of 19b under alkaline condition gave the desired thiophene 20. Representative compounds of the synthesized products were evaluated as antitumor and antioxidant agents. 3-Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of different coumarin derivatives. Newly synthesized compounds were elucidated by analytical and spectral data. Representative compounds of the synthesized products were evaluated as antitumor and antioxidant agents.

Relationship between structure and entropy contributions in an anthraquinone mercapto derivative

The structural and thermodynamic properties of an anthraquinone derivative were studied by means of quantum-chemical calculations. Conformational analysis using ab initio and density functional theory methods revealed 14 low-energy conformers. In order to discuss similarities and differences in entropy of the conformers, the rotational and vibrational contributions to entropy were correlated with changes in conformer structure. The component of the moment of inertia perpendicular to the molecular plane gives significant input to DeltaSrot, whereas the largest contributions to the DeltaSvib have vibrations associated with the tau (S1C20) coordinate.

Synthesis and Quantitative Structure−Antifungal Activity Relationships of Clovane Derivatives against Botrytis cinerea

Twenty-three clovane derivatives, nine described here for the first time, bearing substituents on carbon C-2, have been synthesized and evaluated for their in vitro antifungal activity against the phytopathogenic fungus Botrytis cinerea. The results showed that compounds 9, 14, 16, and 18 bearing nitrogen atoms in the chain attached at C-2 displayed potent antifungal activity, whereas mercapto derivatives 13, 19, and 22 displayed low activity. The antifungal activity showed a clear structure-activity relationship (SAR) trend, which confirmed the importance of the nature of the C-2 chain on the antifungal activity. On the basis of these observations, the metabolism of compounds 8 and 14 by the fungus B. cinerea, and the metabolism of other clovanes by this fungus, described previously, a pro-drug action mechanism for 2-alkoxyclovane compounds is proposed. Quantitative structure-activity relationship (QSAR) studies were performed to rationalize the results and to suggest further optimization, using a topological sub-structural molecular design (TOPS-MODE) approach. The model displayed good fit and predictive capability, describing 85.5% of the experimental variance, with a standard deviation of 9.502 and yielding high values of cross-validation determination coefficients (q2CV-LOO = 0.784 and q2boot = 0.673). The most significant variables were the spectral moments weighted by bond dipole moment (Dip), hydrophobicity (Hyd), and the combined dipolarity/polarizability Abraham molecular descriptor (Ab-pi2H).

Thiols in Ugi‐ and Passerini–Smiles‐Type Couplings

AbstractThe use of the Smiles rearrangement in Ugi‐type couplings with aromatic mercaptans allows for the straightforward, multicomponent formation of α‐arylamino thiocarboxamides. The scope of this new four‐component coupling is further broadened with the use of heterocyclic mercapto derivatives that afford thioamides of high biological interest in one step. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

2-Methyl-1,4-naphthoquinones containing 3-[ N-(ω-mercaptoalkyl)alkanamide] chains: synthesis, self-assembling, and electrochemical properties

2-Methyl-1,4-naphthoquinone derivatives containing 3-[ N-(ω-mercaptoalkyl)alkanamide] chains were synthesized from ω-bromoalkylamine salts of 2-methyl-3-carboxyalkyl-1,4-naphthoquinones in the presence of N,N′-dicyclohexylcarbodiimide at ambient temperature, and then transformed into the corresponding mercapto derivatives. Their self-assembling and electrochemical properties on gold were studied. The influence of an intrachain amide group on the structure and electron transfer properties of self-assembled monolayers were evaluated by comparison with analogous ester and alkyl chain-containing 2-methyl-1,4-naphthoquinones.

Mercapto derivatives of triorganotin Y,C,Y-pincer complexes: Role of Y,C,Y-chelating ligands in a new coordination mode of organotin compounds

We report the use of triorganotin fragments R 2L 1-2Sn containing N,C,N and O,C,O-ligands L 1-2(L 1 = C 6H 3(Me 2NCH 2) 2-2,6 −, L 2 = C 6H 3( t BuOCH 2) 2-2,6 −) on stabilization of both thiol-form in R 2L 1-2Sn-2-SPy (2-SPy = pyridine-2-thiolate) and thione-form in R 2L 1-2Sn(mimt) (mimt = 1-methylimidazole-2-thiolate) of the polar groups. Treatment of ionic organotin compounds [Me 2L 1Sn] +[Cl] − ( 1) and [Ph 2L 2Sn] +[OTf] − ( 2) with appropriate sodium salts Na-2-SPy and Na(mimt) resulted in the isolation of Me 2L 1Sn-2-SPy ( 3), Ph 2L 2Sn-2-SPy ( 4), Me 2L 1Sn(mimt) ( 5), Ph 2L 2Sn(mimt) ( 6). While polar group 2-SPy exists in its thiol-tautomeric form in compounds 3 and 4, the second polar group (mimt) has been stabilized as the thione-tautomeric form by triorganotin fragments R 2L 1-2Sn in compounds 5 and 6. The products were characterized by 1H, 13C and 119Sn NMR and IR spectroscopy, ESI/MS, elemental analyses and structures of 3, 6 were determined by X-ray diffraction study. The reactivity of compound 4 containing non-coordinated nitrogen atom of 2-SPy polar group towards CuCl and AgNO 3 is also reported. The reactions led to isolation of organotin compounds Ph 2L 2SnCl ( 7) and Ph 2L 2SnNO 3 ( 8) as the result of polar group transfer. The mechanism of this reaction has been investigated and compounds Ph 3Sn-2-SPy ( 9) and Ph 2L 2Sn-4-SPy ( 10) (4-SPy = pyridine-4-thiolate) have been prepared for this purpose.

Synthesis and antimicrobial activity of 3-methyl-substituted 6,8-dimethylthiazolo-[2,3-f]xanthines

A series of 3-methyl-substituted 6,8-dimethylthiazolo[2,3-f]xanthines has been synthesized using 3-chloromethyl-6,8-dimethylthiazolo[2,3-f]xanthine and various nucleophiles (hydrazine hydrate, primary aromatic amines, and mercapto derivatives). The target 3-methyl-substituted thiazoloxanthines were obtained with 42–90% yields. The structures were determined using IR, 1H NMR, and mass spectrometry. Most compounds exhibit weak antimicrobial action with respect to C. albicans, E. coli, S. marcencens, C. freundii, Vibrion, B. anthracoides, Klebsiellae spp, Ps. aeruginosa, St. aureus, and Schigellae spp. species with minimum inhibiting concentrations MIC ≥ 100 mg/ml. Comparatively high inhibiting action (MIC = 0.62 and 12.5 mg/ml) on the growth of some test microbes was observed for 3-(hydrazino)methyl-6,8-dimethylthiazolo[2,3-f]xanthine.

Redox-Sensitive Proteins Are Potential Targets of Garlic-Derived Mercaptocysteine Derivatives1–3

Molecular investigations support existing clinical and epidemiological data that garlic-derived allylsulfides reduce cancer risk. Various allylsulfides can diminish progression of cancer cells at either the G1/S or G2/M phase. Allylsulfide derivatives modify redox-sensitive signal pathways and cause growth inhibition, mitotic arrest, and apoptosis induction. Whether allylsulfides modify intracellular redox potentials by affecting the ratio of glutathione:glutathione disulfide and/or by interacting directly with sulfhydryl domains on regulatory or catalytic-signal proteins requires further investigation. To understand the possible biochemical mechanisms contributing to the protective effects of allylsulfides, we investigated the ability of these compounds to undergo enzyme-catalyzed transformations. In addition to catalyzing gamma-elimination reactions, gamma-cystathionase can perform beta-elimination reactions with cysteinyl S-conjugates derived from garlic extracts when the S-alkyl group (R) is larger than ethyl. The reaction products are pyruvate, ammonium, and a sulfur-containing fragment (RSH). beta-Lyase substrates of gamma-cystathionase thus far identified from garlic include: S-allyl-L-cysteine (R=CH2=CHCH2-), S-allylmercapto-L-cysteine (R=CH2=CHCH2S-), and S-propylmercapto-L-cysteine (R=CH3CH2CH2S-). Mercapto derivatives yield persulfide products (RSSH) that are potential sources of sulfane sulfur, which may modify protein function by reacting at important cysteinyl domains. Thus, beta-elimination reactions with cysteine S-conjugates in garlic may modify cancer-cell growth by targeting redox-sensitive signal proteins at sulfhydryl sites, thereby regulating cell proliferation and/or apoptotic responses. These interactions may be useful in identifying efficacy of garlic-derived compounds and/or developing other novel organosulfur compounds that may modify intracellular redox potentials or interact with thiols associated within cysteine domains in regulatory, catalytic, signal, or structural proteins.

A convenient synthesis of long-chain 4-substituted benzyloxycarbonyl alkanethiols for the formation of self assembled monolayers on metal substrates

Abstract New 4-substituted benzyl esters of 16-mercaptohexadecanoic acid were prepared by developing a practicable synthetic procedure and using readily available staring materials. The compounds synthesized have been characterized by NMR, MS, IR spectra and elemental analysis. The mercapto derivatives are precursors for the formation of self-assembled monolayers on metal substrates.

A Synthesis of Heteroaromatic S- and N-β-Glycosides of N-Acetylglucosamine under Phase-Transfer Conditions

The use of crown ethers for a phase transfer-catalyzed synthesis of heteroaromatic glycosides of N-acetylglucosamine was studied. The solid-liquid system and the catalysis by 15-crown-5 were found to provide for both a 100% conversion of the alpha-D-glucosaminyl chloride peracetate and a high reaction rate. The interaction of alpha-D-glucosaminyl chloride peracetate and oxadiazole and triazole mercapto derivatives capable of thiol-thione tautomerism carried out at room temperature in acetonitrile in the presence of anhydrous potassium carbonate and crown ethers was shown to lead to both S- and N-glycosides. The structures of the compounds synthesized were confirmed by X-ray analysis and 13C and 1H NMR spectroscopy.

Preconcentrative separation of palladium(II) using palladium(II) ion-imprinted polymer particles formed with different quinoline derivatives and evaluation of binding parameters based on adsorption isotherm models

Palladium(II) ion-imprinted polymer (IIP) materials were synthesized by thermally polymerizing the ternary complexes of palladium(II) with amino (AQ) or hydroxy (HQ) or mercapto (MQ) derivatives of quinoline and 4-vinyl-pyridine. The functional and crosslinking monomers used during polymerization were 2-hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA). 2,2′-Azobisisobutyronitrile (AIBN) and 2-methoxy ethanol were used as the initiator and porogen, respectively. The resulting polymer materials were dried in an oven at 80 °C, ground and sieved to obtain IIP particles which were then subjected to leaching with 50% (v/v) HCl to obtain the leached palladium(II) IIP particles. Control polymer (CP) particles were also prepared by following the above procedure described for IIP particles. The CP particles, unleached and leached AQ-based IIP particles were then characterized by IR, XRD and microanalysis studies. Analytical studies such as preconcentration of palladium(II) from dilute aqueous solutions and separation studies in the presence of selected noble and base metals which co-exist with palladium(II) in its ore or mineral deposits were systematically studied using CP and IIP particles and are compared. AQ-based IIP particles gave higher percent extraction and selectivity coefficients compared to HQ- or MQ-based IIP particles. Five replicate determinations of 25 μg of palladium(II) present in 500 ml of aqueous solution, when subjected to preconcentration and determination by iodide-Rhodamine 6G procedure gave a mean absorbance of 0.104 with a relative standard deviation of 2.25%. The detection limit corresponding to three times the standard deviation of the blank was found to be 5.0 μg of palladium(II) per litre. The rebinding studies using AQ-, HQ- and MQ-based IIPs were carried out and were fitted to the different adsorption isotherm models, viz. Langmuir (L), Freundlich (F) and Langmuir–Freundlich (LF). These adsorption models were used for the evaluation of binding parameters and in elucidating the nature and type of bonding in the IIPs. The results of rebinding experiments showed discrimination between the three IIPs based on the donor atoms of the ligands.

Synthesis of Some Thienotetrahydroquinoline Derivatives

Abstract2‐Thioxo‐1,2,5,6,7,8‐hexahydroquinoline‐3‐carbonitrile (2) was easily S‐alkylated to produce alkyl mercapto derivatives 3a‐g. The latter compounds were cyclized to afford thienotetrahydroquinolines 4a‐g. Several pyrimidothienotetrahydroquinolines 5a‐d, and 6a‐d were obtained from the condensation of compounds 4c‐f with different reagents.o‐Aminocarbohydrazide derivative 11 was reacted with aromatic aldehydes, acetylacetone, nitrous acid and CS2 to afford compounds 12–15. Compound 24 was coupled with aryldiazonium chloride to afford arylazo derivatives 25. Also it condensed with aromatic aldehydes to give arylidene derivatives 26. The latter compounds were reacted with malononitrile to give pyrano derivative 27.

Syntheses and characterization of some chloro, methoxy, and mercapto derivatives of [Ru(η 2-2,2′-bipyridine) 3] 2+2PF 6 − : crystal and molecular structures of [Ru(η 2-2,2′-bipyridine) 2(η 2-4,4′-(X) 2-2,2′-bipyridine)] 2+2PF 6 − (X=Cl, OCH 3)

Nucleophilic substitutions involving [Ru(η 2-bipy) 2{η 2-bipy–Cl 2}] 2+ (bipy=2,2′-bipyridine; bipy–Cl 2=4,4′-dichloro-2,2′-bipyridine) and OCH 3 − , SH −, and S(4-CH 3–C 6H 4) − were carried out, and the resulting disubstituted products were characterized analytically and spectroscopically. Moreover, [Ru(η 2-bipy) 2{η 2-bipy–Cl 2}] 2+2PF 6 − and [Ru(η 2-bipy) 2{η 2-bipy–(OCH 3) 2}] 2+2PF 6 − were structurally characterized by single crystal X-ray diffraction.

Ion-induced interfacial dynamics of phospholipid monolayers.

Ion-induced interfacial dynamics of phospholipid monolayers were studied by various electrochemical techniques. The lipid monolayers were constructed by using the mercapto derivatives of natural lipids that were self-assembled directly onto gold electrode surfaces in a tails-down fashion. The supported lipid assemblies appeared to act as rather effective electron-tunneling barriers with K3Fe(CN)6 as the redox probe, despite a relatively low surface coverage and/or a disordered surface structure. Upon the stimulation by alkaline-earth ions, the lipid layers appeared to undergo surface reorganization, exposing part of the electrode surface which resulted in the formation of microscopic mass-transfer lipid channels. The dimensions and/or the number of these channels increased with increasing ion concentrations, and this ion-gate effect appeared to be quite selective, with the most pronounced effects observed among the series of alkaline-earth ions with Ca2+.

Electrochemical Studies of Water-Soluble Palladium Nanoparticles

Aqueous-soluble monolayer-protected palladium nanoparticles were synthesized by hydrogen reduction of Pd(II) in a water solution. The particles were then further functionalized by incorporating multiple copies of mercapto derivatives of viologen into the particle protecting monolayers. The electrochemistry of the viologen moieties with the particles dissolved in solution or immobilized onto electrode surfaces was carefully studied using various electrochemical techniques. The particle molecular capacitance was evaluated by rotating-disk-electrode voltammetry and the electron-transfer rate constant of the particle-bound viologen moieties was estimated by impedance measurements.

SYNTHESIS AND REACTIONS OF SOME IMIDAZOPYRIMIDO (PYRIDO)THIENO [2,3-b]QUINOXALINE DERIVATIVES

2-Amino-3(4,5-dihydro-1H-imidazol-2-yl)thieno[2,3-b]quinoxaline 2 was prepared and then allowed to react with nitrous acid, triethyl orthoformate. acetic anhydride and carbon disulfide to give the imidazotriazinothienoquinoxaline 3 and imidazopyrimidothienoquinoxaline 4–6 respectively. Starting with thione 6 a series of S-ubstituted mercapto derivatives 7–10 was obtained. Reaction of 2-amino-3-carbonitrile-thieno[2,3-b]quinoxaline 1 with acrylonitrile, malononitrile andor arylidine malononitrile gave pyridothienoquinoxaline derivatives 11-13.

Brightness reversion of mechanical pulps VIII. Investigation of synergistic photostabilization methods for high-yield pulp

Recent advances in the photostabilization of mechanical pulp suggest that the use of additive mixtures may provide optimal protection against brightness reversion. Some of the most promising additive mixtures reported in the literature include the use of a UV absorber, such as 2,4-dihydroxybenzophenone, and a radical scavenger. The mechanistic basis of this synergistic effect was explored by monitoring the photostability of benzophenone during brightness reversion. These studies demonstrated that the benzophenone additives were stable under the initial photolysis conditions. The use of mercapto derivatives of benzophenone did not enhance the photostabilization effect, suggesting that the thiol additive and UV absorber need not be in close association with each other for the observed photostabilization effects to occur.

Two new chiral equivalents of H 2S: a thio- and a dithiocarboxylic acid

The syntheses of the two new chiral mercapto derivatives ( R)-2-[ N-(1-phenylethyl)-amino]-1-cyclopentenedithiocarboxylic acid, 5, and (1 S,4 R)-1-(4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane)thiocarboxylic acid, 9, are described through easy transformations in good yields.

Synthesis of chloro and mercapto derivatives of 1-(2-deoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)uracil

Synthesis of chloro and mercapto derivatives of 1-(2-deoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)uracil