RESUMO
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.
Assuntos
Compostos Bicíclicos com Pontes/química , Ácidos Carboxílicos/química , Compostos de Sulfônio/química , Compostos Bicíclicos com Pontes/síntese química , Ácidos Carboxílicos/síntese química , Cristalografia por Raios X , Ciclopropanos/síntese química , Ciclopropanos/química , Modelos Moleculares , Compostos de Sulfônio/síntese químicaRESUMO
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.
Assuntos
Bactérias/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Compostos de Sulfônio/farmacologia , Tensoativos/farmacologia , Tiofenos/farmacologia , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/química , Relação Estrutura-Atividade , Compostos de Sulfônio/síntese química , Compostos de Sulfônio/química , Tensoativos/síntese química , Tensoativos/química , Tiofenos/síntese química , Tiofenos/químicaRESUMO
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.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Portadores de Fármacos/farmacologia , Compostos de Sulfônio/farmacologia , Antibacterianos/síntese química , Antibacterianos/toxicidade , Derivados de Benzeno/síntese química , Derivados de Benzeno/farmacologia , Derivados de Benzeno/toxicidade , Linhagem Celular Tumoral , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Escherichia coli/efeitos dos fármacos , Humanos , Lipídeos/síntese química , Lipídeos/farmacologia , Lipídeos/toxicidade , Staphylococcus aureus/efeitos dos fármacos , Compostos de Sulfônio/síntese química , Compostos de Sulfônio/toxicidadeRESUMO
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.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Cromonas/síntese química , Cromonas/farmacologia , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromonas/química , Cristalografia por Raios X , Humanos , Modelos Moleculares , Neoplasias/tratamento farmacológico , Sais/síntese química , Sais/química , Compostos de Sulfidrila/química , Compostos de Sulfônio/síntese química , Compostos de Sulfônio/químicaRESUMO
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.
Assuntos
Morfolinas/química , Morfolinas/farmacologia , Agonistas Nicotínicos/química , Agonistas Nicotínicos/farmacologia , Oniocompostos/química , Oniocompostos/farmacologia , Compostos de Sulfônio/química , Compostos de Sulfônio/farmacologia , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Compostos de Amônio/síntese química , Compostos de Amônio/química , Compostos de Amônio/farmacologia , Animais , Humanos , Modelos Moleculares , Morfolinas/síntese química , Agonistas Nicotínicos/síntese química , Oniocompostos/síntese química , Compostos de Sulfônio/síntese química , Xenopus laevis , Receptor Nicotínico de Acetilcolina alfa7/metabolismoRESUMO
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).
Assuntos
Compostos Alílicos/química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Pirrolidinonas/química , Compostos Alílicos/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Pirrolidinonas/síntese química , Estereoisomerismo , Compostos de Sulfônio/síntese química , Compostos de Sulfônio/químicaRESUMO
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.
Assuntos
Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Galactose/análogos & derivados , Isomerases/antagonistas & inibidores , Difosfato de Uridina/análogos & derivados , Biocatálise , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Galactose/metabolismo , Hidroxilação , Isomerases/metabolismo , Mycobacterium tuberculosis/enzimologia , Compostos de Selênio/síntese química , Compostos de Selênio/química , Compostos de Selênio/farmacologia , Compostos de Sulfônio/síntese química , Compostos de Sulfônio/química , Compostos de Sulfônio/farmacologia , Difosfato de Uridina/metabolismoRESUMO
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.
Assuntos
Radioisótopos de Flúor , Marcação por Isótopo , Sais , Compostos de Sulfônio , Animais , Camundongos , Modelos Animais , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Compostos de Sulfônio/síntese química , Tomografia Computadorizada por Raios XRESUMO
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.
Assuntos
Óxidos/química , Silanos/química , Compostos de Sulfônio/síntese química , Compostos Heterocíclicos , Estrutura Molecular , Estereoisomerismo , Compostos de Sulfônio/químicaRESUMO
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.
Assuntos
Acetamidas/síntese química , Cianetos/química , Iminas/síntese química , Compostos de Sulfônio/síntese química , Acetamidas/química , Catálise , Iminas/química , Estrutura Molecular , Estereoisomerismo , Compostos de Sulfônio/químicaRESUMO
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.
Assuntos
Metionina/metabolismo , Roseobacter/metabolismo , Água do Mar/microbiologia , Compostos de Sulfônio/metabolismo , Enxofre/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Metionina/biossíntese , Padrões de Referência , Compostos de Sulfônio/síntese química , Compostos de Sulfônio/química , VolatilizaçãoRESUMO
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.
Assuntos
Compostos de Benzilideno/síntese química , Iminas/química , Ácidos de Lewis/química , Compostos de Sulfônio/síntese química , Compostos de Benzilideno/química , Brometos/química , Compostos de Magnésio/química , Estrutura Molecular , Compostos Organometálicos/química , Estereoisomerismo , Compostos de Sulfônio/químicaRESUMO
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.
Assuntos
Polímeros/química , Compostos de Sulfônio/síntese química , Elétrons , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
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.
Assuntos
Alcinos/química , Paládio/química , Compostos de Sulfônio/química , Compostos de Sulfônio/síntese química , Ligação de Hidrogênio , Metilação , Estrutura MolecularRESUMO
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.
Assuntos
Gás de Mostarda/análogos & derivados , Compostos de Sulfônio/síntese química , Hidrólise , Cinética , Estrutura Molecular , Gás de Mostarda/química , Sais/síntese química , Sais/química , Compostos de Sulfônio/químicaRESUMO
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.
Assuntos
Aderência Bacteriana/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Osteoblastos/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Animais , Células Cultivadas , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Embrião de Mamíferos , Teste de Materiais , Testes de Sensibilidade Microbiana , Osseointegração/efeitos dos fármacos , Osteoblastos/fisiologia , Osteogênese/efeitos dos fármacos , Polímeros/síntese química , Polímeros/química , Polímeros/farmacologia , Poliestirenos/síntese química , Poliestirenos/química , Poliestirenos/farmacologia , Ratos , Ratos Wistar , Sódio/química , Sódio/farmacologia , Staphylococcus aureus/fisiologia , Compostos de Sulfônio/síntese química , Compostos de Sulfônio/química , Compostos de Sulfônio/farmacologia , Titânio/química , Titânio/farmacologiaRESUMO
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.
Assuntos
Iminas/química , Iminas/síntese química , Nitrilas/química , Compostos de Sulfônio/química , Compostos de Sulfônio/síntese química , Cristalografia por Raios X , Estrutura Molecular , EstereoisomerismoRESUMO
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.
Assuntos
Amidas/síntese química , Compostos de Epóxi/síntese química , Propionatos/síntese química , Compostos de Sulfônio/síntese química , Amidas/química , Aminoácidos/química , Compostos de Epóxi/química , Estrutura Molecular , Propionatos/química , Sais/química , Estereoisomerismo , Compostos de Sulfônio/químicaRESUMO
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.
Assuntos
Química Click , Compostos de Sulfônio/química , Estrutura Molecular , Compostos de Sulfônio/síntese químicaRESUMO
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.