RESUMO
This paper discloses a transition metal-free selective C-H dithiocarbamation of drug skeletons using disulfiram (DSF) in the presence of KI/K2S2O8 in DMF/H2O. Drug skeletons, including 5-aminopyrazoles, indoles, pyrroloquinoline, and Julolidine, underwent C-H dithiocarbamation smoothly to afford a variety of drug-like molecules in moderate to good yields. It was found that the in situ formed 5-aminopyrazole iodide is the key intermediate for the dithiocarbamation. Bioassay results show that some of these N-heterocyclic dithiocarbamate derivatives exhibit good antifungal activity against Colletotrichum gloeosprioides and Fusarium oxysporum, F. proliferatum, Fusarium solani, Geotrichum candidum, Penicillium digitatum, Penicillium italicum, Phyricularia grisea.
Assuntos
Antifúngicos/farmacologia , Colletotrichum/efeitos dos fármacos , Fusarium/efeitos dos fármacos , Geotrichum/efeitos dos fármacos , Penicillium/efeitos dos fármacos , Tiocarbamatos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Derivados de Benzeno/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Estereoisomerismo , Tiocarbamatos/síntese química , Tiocarbamatos/químicaRESUMO
Achieving site selectivity in carbon-hydrogen (C-H) functionalization reactions is a long-standing challenge in organic chemistry. The small differences in intrinsic reactivity of C-H bonds in any given organic molecule can lead to the activation of undesired C-H bonds by a non-selective catalyst. One solution to this problem is to distinguish C-H bonds on the basis of their location in the molecule relative to a specific functional group. In this context, the activation of C-H bonds five or six bonds away from a functional group by cyclometallation has been extensively studied. However, the directed activation of C-H bonds that are distal to (more than six bonds away) functional groups has remained challenging, especially when the target C-H bond is geometrically inaccessible to directed metallation owing to the ring strain encountered in cyclometallation. Here we report a recyclable template that directs the olefination and acetoxylation of distal meta-C-H bonds--as far as 11 bonds away--of anilines and benzylic amines. This template is able to direct the meta-selective C-H functionalization of bicyclic heterocycles via a highly strained, tricyclic-cyclophane-like palladated intermediate. X-ray and nuclear magnetic resonance studies reveal that the conformational biases induced by a single fluorine substitution in the template can be enhanced by using a ligand to switch from ortho- to meta-selectivity.
Assuntos
Aminas/química , Carbono/química , Hidrogênio/química , Alcenos/química , Compostos de Anilina/química , Benzilaminas/química , Desenho de Fármacos , Quinolinas/químicaRESUMO
Dialkyl azo compounds were found to be effective alkyl radical sources for direct alkyl sulfuration with imidazopyridines using elemental sulfur under metal-free conditions. Iodine, an inexpensive and mild reagent, could promote alkyl sulfuration. A variety of quaternary cyanoalkyl radicals were successfully coupled with elemental sulfur. A subsequent C-H sulfuration of imidazopyridines afforded a diverse array of imidazopyridine derivatives bearing cyanoalkylthio groups. The cyano group could be modified and further underwent condensation with 2-aminothiazole to afford an interesting heterocyclic amide. Control experiments showed that iodine could greatly suppress the self-coupling of cyanoalkyl radicals, thus making the sulfuration proceed smoothly.
RESUMO
A copper-catalyzed DTBP oxidative dual C-H sulfurization has been developed for the direct thiocarbamation of imidazopyridines using a combination of elemental sulfur and formamides as carbamothioyl surrogates. NBS (bromo succinimide) was found to promote the thiocarbamation in good yields. This dual C-H sulfurization strategy enables access to a wide range of carbamothioyl imidazoheterocycles without the use of highly toxic phosgene.
RESUMO
Pyrazole constitutes an important heterocyclic family covering a broad range of synthetic as well as natural products that exhibit numerous chemical, biological, agrochemical and pharmacological properties. In order to explore compounds with good fungicidal activity, a series of new pyrazole derivatives containing 5-phenyl-2-furan were designed and synthesized. In vitro and in vivo fungicidal activities were evaluated and the compound ethyl-1-(5-phenylfuran-2-carbonyl)-5-propyl-1H-pyrazole-3-carboxylate (I8) displayed significant fungicidal activity against various fungi, especially against P. infestans. The structures of the novel pyrazole derivatives were confirmed by 1H NMR, 13C NMR, MS, elemental analysis and X-ray single crystal diffraction. Further study showed that compound I8 might act on the synthesis of cell walls from morphological and ultrastructural studies by SEM and TEM. The results also revealed that compound I8 could block the nutritional transportation leading to cells senescence and death. These results suggested that the novel pyrazole derivatives proved to be promising lead compounds.
Assuntos
Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Furanos/farmacologia , Pirazóis/farmacologia , Antifúngicos/síntese química , Parede Celular/efeitos dos fármacos , Furanos/síntese química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pirazóis/síntese química , Relação Estrutura-AtividadeRESUMO
A single and simple ortho-sulfonyl benzonitrile template was developed to achieve remote C-H olefination of six different classes of N-heterocycles. We demonstrate that, by varying precatalysts and conditions, the same template can be applied to the remote C-H activation of six structurally distinct heterocyclic scaffolds, and the site-selectivity can be predicted based on distance and geometry. Furthermore, this new development shows that template-directed remote C-H activation is possible through macrocyclopalladation processes with smaller ring sizes.
RESUMO
1,1,1,3,3,3-Hexafluoropropan-2-ol (HFIP) was found to be effective for the Bischler indole synthesis under microwave irradiation in the absence of a metal catalyst. Under the catalysis of HFIP, a wide range of α-amino arylacetones were successfully transformed into indole derivatives with moderate to good yields.
Assuntos
Indóis/química , Micro-Ondas , Catálise , Ciclização , Estrutura MolecularRESUMO
A new ring expansion of 2-aminobenzothiazoles with alkynyl carboxylic acids was developed, which allows for one-pot synthesis of 1,4-benzothiazines in moderate to excellent yields. The cascade reaction was achieved through decarboxylative coupling, nucleophilic ring-opening reaction and intramolecular hydroamination process.
Assuntos
Ácidos Carboxílicos/química , Cobre/química , Tiazinas/síntese química , Tiazóis/química , Catálise , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Solventes/química , TemperaturaRESUMO
meta-C-H olefination, arylation, and acetoxylation of indolines have been developed using nitrile-containing templates. The combination of a monoprotected amino acid ligand and the nitrile template attached at the indolinyl nitrogen via a sulfonamide linkage is crucial for the meta-selective C-H functionalization of electron-rich indolines that are otherwise highly reactive toward electrophilic palladation at the para-positions. A wide range of synthetically important and advanced indoline analogues are selectively functionalized at the meta-positions.
RESUMO
A novel Lewis acid catalyzed annulation reaction has been established for the synthesis of benzocyclohepta[b]indoles. This method represents a new annulation strategy to a seven-membered carbocyclic ring system from two 3-(1H-isochromen-1-yl)-1H-indole molecules using Cu(OTf)2 catalyst; moreover, the products, benzocyclohepta[b]indoles, can be used as the rapid mercuric ion colorimetric detection reagents.
Assuntos
Cromanos/química , Cicloeptanos/química , Indóis/química , Ácidos de Lewis/química , Mesilatos/química , Catálise , Estrutura MolecularRESUMO
A new and selective C-N bond oxidative cleavage method to 3-acylated indoles by Pd-catalyzed oxidative cross coupling of indoles with α-amino carbonyl compounds has been developed; moreover, one-pot synthesis of 3-acylated indoles from 2-ethynylanilines and α-amino carbonyl compounds has also been established. Importantly, the products 3-acylated indoles can be used to construct polyheterocyclic compound, which can be employed as efficient probes for Hg(2+) and Fe(3+).
Assuntos
Aminas/química , Indóis/química , Indóis/síntese química , Cetonas/síntese química , Compostos Organometálicos/química , Paládio/química , Acilação , Catálise , Cetonas/química , Estrutura Molecular , OxirreduçãoRESUMO
A palladium- and copper-catalyzed tandem N-H/C-H bond functionalization reaction of ortho-(2-chlorovinyl)bromobenzenes with indoles and pyrroles has been developed. A variety of CF(3)-containing indolo- and pyrrolo[2,1-a]isoquinolines were prepared in moderate to good yields via the cyclization of 1-bromo-2-(2-chloro-3,3,3-trifluoroprop-1-enyl)benzenes with indoles and pyrroles.
Assuntos
Bromobenzenos/química , Cobre/química , Indóis/química , Indóis/síntese química , Isoquinolinas/química , Isoquinolinas/síntese química , Paládio/química , Pirróis/química , Pirróis/síntese química , Catálise , Estrutura MolecularRESUMO
Methicillin-resistant Staphylococcus aureus (MRSA) poses a severe threat to public health and safety. The discovery and development of novel anti-MRSA drugs with a new mode of action are a challenge. In this study, a class of novel aryloxyethyl propiolates and their homologues as anti-MRSA agents have been designed and synthesized based on phenoxyethanol, of which compound II-39 showed high inhibitory activity against MRSA with an MIC of 0.78 µg/mL and an MBC of 3.13 µg/mL, which was better than that of vancomycin. Compound II-39 could destroy the cell wall and cell membrane, inhibited the formation of a biofilm, and bound to the DNA of MRSA through the electrostatic and groove interaction. Proteomic and metabolomic studies revealed that compound II-39 affected multiple intracellular metabolic pathways of MRSA. Notably, compound II-39 could effectively inhibit the expression of CrtPQMN proteins and block the biosynthesis of virulence factor (staphyloxanthin). Thus, aryloxyethyl propiolates and their homologues are promising anti-MRSA agents with multiple targets.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Proteômica , Antibacterianos/farmacologiaRESUMO
Herein we report the first versatile and expeditious method for the site-selective C-H fluoromethylation of aryl iodides via Pd/norbornene cooperative catalysis, which could work as a robust toolbox for the diversity-oriented synthesis (DOS) of fluoromethylated arenes. This methodology features the use of the low-cost industrial raw material CH2IF as the fluoromethyl source, an excellent functional group tolerance, and a broad ipso termination scope and can be expanded to the late-stage modification of biorelevant molecules.
RESUMO
A novel approach towards the efficient assembly of ß-fluoroalkylated arenes is presented here based on Pd/norbornene cooperative catalysis, which features an excellent functional group tolerance, as well as a broad ipso termination scope. The mild reaction conditions enabled the diversity-oriented synthesis (DOS) of the 13 and 14-membered fluorinated macrolactones which is extremely challenging otherwise. This new abstract could be used instead of our old version.
Assuntos
Norbornanos , Paládio , CatáliseRESUMO
An efficient tandem route to the synthesis of iodoisoquinoline-fused benzimidazole derivatives including an iodocyclization strategy has been developed. In the presence of CuI, a variety of 2-ethynylbenzaldehydes underwent the tandem reaction with benzenediamines and iodine to afford the corresponding iodoisoquinoline-fused benzimidazoles in moderate to good yields.
Assuntos
Benzaldeídos/química , Benzimidazóis/síntese química , Iodo/química , Isoquinolinas/síntese química , Benzimidazóis/química , Ciclização , Isoquinolinas/química , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
A copper-catalyzed thiolation annulation reaction of 2-bromo alkynylbenzenes with sodium sulfide has been developed. In the presence of CuI and TMEDA, a variety of 2-substituted benzo[b]thiophenes were readily prepared in moderate to good yields by the reaction of 2-bromo alkynylbenzenes and Na(2)S·9H(2)O.
Assuntos
Benzeno/química , Compostos Organometálicos/química , Sulfetos/química , Tiofenos/síntese química , Catálise , Cromatografia em Camada Fina , Cromatografia Gasosa-Espectrometria de Massas , Espectroscopia de Ressonância Magnética , Espectrofotometria InfravermelhoRESUMO
Foodborne microbial infestation seriously threatens food security, and the development of low-risk food preservatives is highly needed in food production. For discovering novel flavor molecules with antiseptic function, novel 2-methyl-3-furyl sulfide flavor derivatives were synthesized and evaluated. A wide range of 2-methyl-3-furyl sulfide derivatives were synthesized by reactions of 2-methyl-3-furyl disulfide with cyclic ethers, amides, ketones, and epoxides. All of these compounds have special aroma characteristics and low aroma thresholds. The antimicrobial activity of these compounds against test foodborne bacterial or fungal strains (Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Salmonella paratyphi, Listeria monocytogenes, Vibrio parahemolyticus, Penicillium italicum, Aspergillus niger, Mucor racemosus, Rhizopus oryzae) was examined. It was found that fifteen compounds (3a, 3b, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3l, 3m, 5a, 5b, 5f) have antimicrobial activity against different foodborne bacterial or fungal strains. Significantly, the antimicrobial activity of the flavor compounds (3b, 3d, 3e, 3i, 3j, 3l, 3m) is better than that of the control group (penicillin, amphotericin B and thiram), and they are promising preservatives for food production.
RESUMO
Copper-catalyzed double thiolation reaction of 1,4-dihalides with sulfides has been developed for selectively synthesizing 2-trifluoromethyl benzothiophenes and benzothiazoles. In the presence of CuI, a variety of 2-halo-1-(2-haloaryl)-3,3,3-trifluoropropylenes smoothly underwent the thiolation annulation with Na(2)S to afford 2-trifluoromethyl benzothiophenes in moderate to good yields. Moreover, the conditions are compatible with N-(2-haloaryl)trifluoroacetimidoyl chlorides in the presence of NaHS and K(3)PO(4), leading to 2-trifluoromethyl benzothiazoles.
Assuntos
Benzotiazóis/síntese química , Cobre/química , Compostos de Sulfidrila/química , Sulfetos/química , Tiofenos/síntese química , Benzotiazóis/química , Catálise , Estrutura Molecular , Estereoisomerismo , Tiofenos/químicaRESUMO
Sulfur-containing spice compounds possess diverse biological functions and play an important role in food, chemicals, pharmaceuticals, and agriculture. The development of functional spices has become increasingly popular, especially for medicinal functions for dietary health. Thus, this review focuses on the properties and functions of sulfur-containing spice compounds, including antioxidant, anti-inflammatory, antiobesity, anticancer, antibacterial, and insecticidal functions, among others. Developments over the last five years concerning the properties of sulfur-containing spice compounds are summarized and discussed.