RESUMEN
We have been interested in the reactivities of small-ring compounds and have reported reactions that proceed through cyclopropane intermediates starting from coumarin derivatives bearing an electron-withdrawing group at the 3-position or 2-oxo-2H-pyran-3-carboxylate derivatives and dimethylsulfoxonium methylide. This time, the reaction between 3-oxa-2-oxobicyclo[4.2.0]oct-4-ene-1-carboxylate and dimethylsulfoxonium methylide has been investigated. 3a,4,5,7a-Tetrahydro-7-hydroxybenzofuran-6-carboxylate and/or 2-hydroxybicyclo[4.1.0]hept-2-ene-3-carboxylate were obtained. The compounds were characterized using various spectral and X-ray crystallographic techniques. A plausible reaction mechanism has been discussed. This reaction was applied to some 3-oxa-2-oxobicyclo[4.2.0]oct-4-ene-1-carboxylate derivatives to clarify the generality.
Asunto(s)
Compuestos Bicíclicos con Puentes/química , Ácidos Carboxílicos/química , Compuestos de Sulfonio/química , Compuestos Bicíclicos con Puentes/síntesis química , Ácidos Carboxílicos/síntesis química , Cristalografía por Rayos X , Ciclopropanos/síntesis química , Ciclopropanos/química , Modelos Moleculares , Compuestos de Sulfonio/síntesis químicaRESUMEN
Recent advances in the development of quaternary ammonium compounds (QACs) have focused on new structural motifs to increase bioactivity, but significantly less studied has been the change from ammonium- to sulfonium-based disinfectants. Herein, we report the synthesis of structurally analogous series of quaternary ammonium and trivalent sulfonium compounds (TSCs). The bioactivity profiles of these compounds generally mirror each other, and the antibacterial activity of sulfonium-based THT-18 was found to be comparable to the commercial disinfectant, BAC. The development of these compounds presents a new avenue for further study of disinfectants to combat the growing threat of bacterial resistance.
Asunto(s)
Bacterias/efectos de los fármacos , Compuestos de Amonio Cuaternario/farmacología , Compuestos de Sulfonio/farmacología , Tensoactivos/farmacología , Tiofenos/farmacología , Relación Dosis-Respuesta a Droga , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Compuestos de Amonio Cuaternario/síntesis química , Compuestos de Amonio Cuaternario/química , Relación Estructura-Actividad , Compuestos de Sulfonio/síntesis química , Compuestos de Sulfonio/química , Tensoactivos/síntesis química , Tensoactivos/química , Tiofenos/síntesis química , Tiofenos/químicaRESUMEN
We describe a novel class of stimuli-sensitive sulfonium-based synthetic lipids, which exhibit several favorable biophysical properties of phospholipids. The potent sulfonium-based lipid was successfully disassembled by glutathione to release the encapsulated drug molecules in a controlled manner. The cationic lipid also showed lower cytotoxicity against mammalian cells and displayed moderate antibacterial activities.
Asunto(s)
Antibacterianos/farmacología , Antineoplásicos/farmacología , Doxorrubicina/farmacología , Portadores de Fármacos/farmacología , Compuestos de Sulfonio/farmacología , Antibacterianos/síntesis química , Antibacterianos/toxicidad , Derivados del Benceno/síntesis química , Derivados del Benceno/farmacología , Derivados del Benceno/toxicidad , Línea Celular Tumoral , Portadores de Fármacos/síntesis química , Portadores de Fármacos/toxicidad , Escherichia coli/efectos de los fármacos , Humanos , Lípidos/síntesis química , Lípidos/farmacología , Lípidos/toxicidad , Staphylococcus aureus/efectos de los fármacos , Compuestos de Sulfonio/síntesis química , Compuestos de Sulfonio/toxicidadRESUMEN
A new Darzens reaction of thioisatins and sulfonium salts has, for the first time, been reported. This reaction allows efficient access to thiochromenone derivatives in good to excellent yields under mild reaction conditions. The substrate scope includes both electron-withdrawing and electron-donating groups on both the thioisatins and sulfonium salts. Moreover, some of the synthesized thiochromenone derivatives have been found to show potent anticancer activities against six different cancer cell lines using the methylthiazoltetrazolium (MTT) assay.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Cromonas/síntesis química , Cromonas/farmacología , Compuestos de Sulfhidrilo/síntesis química , Compuestos de Sulfhidrilo/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cromonas/química , Cristalografía por Rayos X , Humanos , Modelos Moleculares , Neoplasias/tratamiento farmacológico , Sales (Química)/síntesis química , Sales (Química)/química , Compuestos de Sulfhidrilo/química , Compuestos de Sulfonio/síntesis química , Compuestos de Sulfonio/químicaRESUMEN
Weak partial agonists that promote a desensitized state of the α7 nicotinic acetylcholine receptor (nAChR) have been associated with anti-inflammatory effects. Exemplar compounds feature a tertiary or quaternary ammonium group. We report the synthesis, structure, and electrophysiological evaluation of 1-ethyl-4-phenylthiomorpholin-1-ium triflate, a weak partial agonist with a sulfonium isostere of the ammonium pharmacophore. These results offer new insights in understanding nAChR-ligand interactions and provide a new chemical space to target the α7 nAChR.
Asunto(s)
Morfolinas/química , Morfolinas/farmacología , Agonistas Nicotínicos/química , Agonistas Nicotínicos/farmacología , Compuestos Onio/química , Compuestos Onio/farmacología , Compuestos de Sulfonio/química , Compuestos de Sulfonio/farmacología , Receptor Nicotínico de Acetilcolina alfa 7/agonistas , Compuestos de Amonio/síntesis química , Compuestos de Amonio/química , Compuestos de Amonio/farmacología , Animales , Humanos , Modelos Moleculares , Morfolinas/síntesis química , Agonistas Nicotínicos/síntesis química , Compuestos Onio/síntesis química , Compuestos de Sulfonio/síntesis química , Xenopus laevis , Receptor Nicotínico de Acetilcolina alfa 7/metabolismoRESUMEN
A diastereoselective new approach for the synthesis of trans-4-hydroxy-5-allyl-2-pyrrolidinone 9 has been developed through In-mediated allylation of α-chiral aldimine 8 with allyl bromide. The stereochemistry at the C-2 stereogenic center of 9 was controlled by both the α-OTBS substitution and the sulfinamide moiety. The utility of this asymmetric allylation is demonstrated by the asymmetric syntheses of epohelmins A (4) and B (10).
Asunto(s)
Compuestos Alílicos/química , Compuestos Bicíclicos Heterocíclicos con Puentes/síntesis química , Pirrolidinonas/química , Compuestos Alílicos/síntesis química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Pirrolidinonas/síntesis química , Estereoisomerismo , Compuestos de Sulfonio/síntesis química , Compuestos de Sulfonio/químicaRESUMEN
Uridine diphosphate-galactopyranose mutase (UGM), an enzyme found in many eukaryotic and prokaryotic human pathogens, catalyzes the interconversion of UDP-galactopyranose (UDP-Galp) and UDP-galactofuranose (UDP-Galf), the latter being used as the biosynthetic precursor of the galactofuranose polymer portion of the mycobacterium cell wall. We report here the synthesis of a sulfonium and selenonium ion with an appended polyhydroxylated side chain. These compounds were designed as transition state mimics of the UGM-catalyzed reaction, where the head groups carrying a permanent positive charge were designed to mimic both the shape and positive charge of the proposed galactopyranosyl cation-like transition state. An HPLC-based UGM inhibition assay indicated that the compounds inhibited about 25% of UGM activity at 500 µM concentration.
Asunto(s)
Diseño de Fármacos , Inhibidores Enzimáticos/farmacología , Galactosa/análogos & derivados , Isomerasas/antagonistas & inhibidores , Uridina Difosfato/análogos & derivados , Biocatálisis , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Galactosa/metabolismo , Hidroxilación , Isomerasas/metabolismo , Mycobacterium tuberculosis/enzimología , Compuestos de Selenio/síntesis química , Compuestos de Selenio/química , Compuestos de Selenio/farmacología , Compuestos de Sulfonio/síntesis química , Compuestos de Sulfonio/química , Compuestos de Sulfonio/farmacología , Uridina Difosfato/metabolismoRESUMEN
Positron emission tomography (PET) is unique in that it allows quantification of biochemical processes in vivo, but difficulties with preparing suitably labelled radiotracers limit its scientific and diagnostic applications. Aromatic [(18)F]fluorination of drug-like small molecules is particularly challenging as their functional group compositions often impair the labelling efficiency. Herein, we report a new strategy for incorporation of (18)F into highly functionalized aromatic compounds using sulfonium salts as leaving groups. The method is compatible with pharmacologically relevant functional groups, including aliphatic amines and basic heterocycles. Activated substrates react with [(18)F]fluoride at room temperature, and with heating the reaction proceeds in the presence of hydrogen bond donors. Furthermore, the use of electron rich spectator ligands allows efficient and regioselective [(18)F]fluorination of non-activated aromatic moieties. The method provides a broadly applicable route for (18)F labelling of biologically active small molecules, and offers immediate practical benefits for drug discovery and imaging with PET.
Asunto(s)
Radioisótopos de Flúor , Marcaje Isotópico , Sales (Química) , Compuestos de Sulfonio , Animales , Ratones , Modelos Animales , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Compuestos de Sulfonio/síntesis química , Tomografía Computarizada por Rayos XRESUMEN
The addition of a broad variety of substituted aromatic and heterocyclic silanes to chiral N-tert-butanesulfinylimines has been achieved providing 1,1-diaryl and diheterocyclic substituted sulfinamides with excellent diastereoselectivity in all cases. Employing Me3SiO(-)/Bu4N(+) as the Lewis base activator for silicon allowed a general procedure for all silane reagents, including the less reactive aromatic derivatives. Evidence that the diastereoselective additions occur via an open transition state is presented.
Asunto(s)
Óxidos/química , Silanos/química , Compuestos de Sulfonio/síntesis química , Compuestos Heterocíclicos , Estructura Molecular , Estereoisomerismo , Compuestos de Sulfonio/químicaRESUMEN
The reaction of isocyanides with N-tert-butanesulfinimines shows remarkable chemoselectivity. ß-Sulfinylamino isocyanides are formed exclusively with aromatic sulfinimines, while α-sulfeneimino acetamides result when using aliphatic derivatives. A mechanism is suggested for the latter transformation, together with an explanation for the observed selectivity. Finally, a scope study is presented for this remarkably chemoselective reaction.
Asunto(s)
Acetamidas/síntesis química , Cianuros/química , Iminas/síntesis química , Compuestos de Sulfonio/síntesis química , Acetamidas/química , Catálisis , Iminas/química , Estructura Molecular , Estereoisomerismo , Compuestos de Sulfonio/químicaRESUMEN
Dimethylsulfoniopropionate (DMSP) is a versatile sulfur source for the production of sulfur-containing secondary metabolites by marine bacteria from the Roseobacter clade. (34)S-labelled DMSP and cysteine, and several DMSP derivatives with modified S-alkyl groups were synthesised and used in feeding experiments that gave insights into the biosynthesis of sulfur volatiles from these bacteria.
Asunto(s)
Metionina/metabolismo , Roseobacter/metabolismo , Agua de Mar/microbiología , Compuestos de Sulfonio/metabolismo , Azufre/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Metionina/biosíntesis , Estándares de Referencia , Compuestos de Sulfonio/síntesis química , Compuestos de Sulfonio/química , VolatilizaciónRESUMEN
The asymmetric nucleophilic 1,2-addition of (S)-N-benzylidene-2-methylpropane-2-sulfinamide with methylmagnesium bromide and methyllithium has been investigated using DFT(B3LYP) computations. The calculated ratio of the two diastereomers agrees with experimental observations, and the factors that determine the diastereomeric ratio are discussed. The preference for the E isomer and the rapid equilibrium between the E and Z isomers of N-tert-butanesulfinyl imine are two key features for understanding the mechanism of this reaction. Methylmagnesium bromide and methyllithium have bifunctional roles, acting as both Lewis acid and nucleophile, and the Lewis acid character plays a determining role in the stereoselectivity of the reaction.
Asunto(s)
Compuestos de Bencilideno/síntesis química , Iminas/química , Ácidos de Lewis/química , Compuestos de Sulfonio/síntesis química , Compuestos de Bencilideno/química , Bromuros/química , Compuestos de Magnesio/química , Estructura Molecular , Compuestos Organometálicos/química , Estereoisomerismo , Compuestos de Sulfonio/químicaRESUMEN
Photoacid generator (PAG) has been widely used as a key component in photoresist for high-resolution patterning with high sensitivity. A novel acrylic monomer, triphenylsulfonium salt methyl methacrylate (TPSMA), was synthesized and includes triphenylsulfonium triflate as a PAG. The poly(MMA-co-TPSMA) (PMT) as a polymer-bound PAG was synthesized with methyl methacrylate (MMA) and TPSMA for electron beam lithography. Characterization of PMT was carried out by NMR and FTIR. The molecular weight was analyzed by GPC. Thermal properties were studied using TGA and DSC. Thecharacterization results were in good agreement with corresponding chemical compositions and thermal stability. PMT was subsequently employed in electron beam lithography and its lithographic performance was confirmed by FE-SEM. This PMT was accomplished to improve the lithographic performance including sensitivity, line width roughness (LWR) and resolution. We found that PMT was capable of 20 nm negative tone patterns with better sensitivity than hydrogensilsesquioxane (HSQ) which is a conventional negative tone resist.
Asunto(s)
Polímeros/química , Compuestos de Sulfonio/síntesis química , Electrones , Microscopía Electrónica de Rastreo , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
A novel palladium-catalyzed methylation protocol for the synthesis of methyl-functionalized internal alkynes has been established. This methylation method is achieved through a C(sp)-C(sp(3)) bond formation process and represents a new synthetic application of sulfonium ylides.
Asunto(s)
Alquinos/química , Paladio/química , Compuestos de Sulfonio/química , Compuestos de Sulfonio/síntesis química , Enlace de Hidrógeno , Metilación , Estructura MolecularRESUMEN
The hydrolysis of 2-chloroethyl ethyl sulfide has been examined in an effort to better understand its mechanism under more concentrated conditions. Two salts formed during hydrolysis were synthesized, and an emphasis was placed on determining their effect on the reaction as it proceeded. Unexpected changes in mechanism were seen when excess chloride was added to the reaction. By measuring rates and product distributions as the products were added back into the hydrolysis, a mechanism was developed. The formation of these sulfonium salts represents additional products in the disappearance of 2-chloroethyl ethyl sulfide with k3 in particular causing a deviation away from expected first-order behavior. Sulfonium salts 3 and 4 do not appear to interconvert, and the system as a whole had fewer pathways available than previously proposed. Initial conditions for studying the hydrolysis were very important and could lead to different conclusions depending on the conditions used. This work will aid in better understanding the hydrolysis of the very toxic chemical warfare agent mustard (bis(2-chloroethyl)sulfide) in the environment and during its decontamination.
Asunto(s)
Gas Mostaza/análogos & derivados , Compuestos de Sulfonio/síntesis química , Hidrólisis , Cinética , Estructura Molecular , Gas Mostaza/química , Sales (Química)/síntesis química , Sales (Química)/química , Compuestos de Sulfonio/químicaRESUMEN
Titanium surface modifications to simultaneously prevent bacterial adhesion but promote bone-cell functions could be highly beneficial for improving implant osseointegration. In the present in vitro study, the effect of sulfonate groups on titanium surfaces was investigated with respect to both S. aureus adhesion and osteoblast functions pertinent to new bone formation. Commercial pure titanium (cpTi) squares were oxydized (Tiox), grafted with poly(sodium styrene sulfonate) groups (Tigraft) by covalent bonding using radical polymerization, and were characterized by infrared spectroscopy (HATR-FTIR) and colorimetry. Bacterial adhesion study showed that Tigraft exhibited high inhibition of S. aureus adhesion S at levels >90 %, when compared to cpTi (P < 0.05). In contrast osteoblasts adhesion was similar on all three titanium surfaces. While the kinetics of cell proliferation were similar on the three titanium surfaces, Alkaline phosphatase-specific activity of osteoblasts cultured on Tigraft surfaces was twofold higher than that observed on either on Tiox or cpTi surfaces (P < 0.01). More importantly, the amount and the distribution of calcium-containing nodules was different. The total area covered by calcium-containing nodules was 2.2-fold higher on the Tigraft as compared to either Tiox or cpTi surfaces (P < 0.01). These results provide evidence that poly(sodium styrene sulfonate) groups grafting on cpTi simultaneously inhibits bacteria adhesion but promote osteoblast function pertinent to new bone formation. Such modified titanium surfaces offer a promising strategy for preventing biofilm-related infections and enhancing osteointegration of implants in orthopaedic and dental applications.
Asunto(s)
Adhesión Bacteriana/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Materiales Biocompatibles Revestidos/farmacología , Osteoblastos/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Animales , Células Cultivadas , Materiales Biocompatibles Revestidos/síntesis química , Materiales Biocompatibles Revestidos/química , Embrión de Mamíferos , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Oseointegración/efectos de los fármacos , Osteoblastos/fisiología , Osteogénesis/efectos de los fármacos , Polímeros/síntesis química , Polímeros/química , Polímeros/farmacología , Poliestirenos/síntesis química , Poliestirenos/química , Poliestirenos/farmacología , Ratas , Ratas Wistar , Sodio/química , Sodio/farmacología , Staphylococcus aureus/fisiología , Compuestos de Sulfonio/síntesis química , Compuestos de Sulfonio/química , Compuestos de Sulfonio/farmacología , Titanio/química , Titanio/farmacologíaRESUMEN
A new chiral (Rs)-2-phenyl-2-propyl sulfinamide has been designed and synthesized; its derived aldimines and ketimines have been applied for asymmetric addition reaction with allylmagnesium bromide. The reaction was conveniently performed at room temperature to give a series of homoallylic amines in high yields (up to quant) and diastereoselectivity (up to >99% de). The pure products were obtained by relying on group-assisted purification (GAP) chemistry to avoid traditional purification methods of column chromatography or recrystallization. The conversion of disulfide to (R(s))-thiosulfinate which contains a newly generated polar group was also confirmed to be of the GAP chemistry in which washing crude product can generate pure enantiomer. The absolute stereochemistry has been determined by X-ray analysis.
Asunto(s)
Iminas/química , Iminas/síntesis química , Nitrilos/química , Compuestos de Sulfonio/química , Compuestos de Sulfonio/síntesis química , Cristalografía por Rayos X , Estructura Molecular , EstereoisomerismoRESUMEN
A new type of chiral sulfonium salts that are characterized by a bicyclic system has been designed and synthesized from α-amino acids. Their corresponding ylides, which were prepared by basic treatment of the sulfonium salts, reacted smoothly with a broad array of simple and chiral aldehydes to provide trans-epoxy amides in reasonable to very good yields and excellent stereoselectivities (>98%). The obtained epoxy amides were found to be useful as synthetic building blocks. Thus, they were reduced into their corresponding epoxy alcohols and subjected to oxirane-ring-opening reactions with different types of nucleophiles.
Asunto(s)
Amidas/síntesis química , Compuestos Epoxi/síntesis química , Propionatos/síntesis química , Compuestos de Sulfonio/síntesis química , Amidas/química , Aminoácidos/química , Compuestos Epoxi/química , Estructura Molecular , Propionatos/química , Sales (Química)/química , Estereoisomerismo , Compuestos de Sulfonio/químicaRESUMEN
A new derivative of the strained 3,3,6,6-tetramethylthiacycloheptyne (TMTH) bearing a functional handle is reported. Following an optimized synthesis, the handle was introduced by mild alkylation of the sulphur atom. The resulting functionalized strained 4,5-didehydro-3,3,6,6-tetramethyl-2,3,6,7-tetrahydrothiepinium (TMTI) proved to be stable and underwent extremely fast [3+2] cycloaddition reaction with benzyl azide in both organic and aqueous solvents. The reaction was equally efficient in cell lysate and serum and therefore opens interesting prospects for chemical-biology applications.
Asunto(s)
Química Clic , Compuestos de Sulfonio/química , Estructura Molecular , Compuestos de Sulfonio/síntesis químicaRESUMEN
This short perspective reports on the synthesis and applications of a class of chiral amino carbonyl compounds, masked oxo-sulfinamides where the amine is protected with an N-sulfinyl moiety and the carbonyl group is protected as the ketal or 1,3-dithiane. These polyfunctionalized chiral building blocks are prepared by addition of organometallic reagents to masked oxo-sulfinimines (N-sulfinyl imines) or the addition of oxo-organometallic reagents and lithio-1,3-dithianes to sulfinimines. Because unmasking of the amino and carbonyl groups results in cyclic imines, these chiral building blocks are particularly useful for the asymmetric synthesis of functionalized nitrogen heterocycles, including prolines, pipecolic acids, pyrrolidines, homotropinones, tropinones, and tropane alkaloids such as cocaine and C-1 cocaine analogues.