RESUMEN
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.
Asunto(s)
Antifúngicos/farmacología , Colletotrichum/efectos de los fármacos , Fusarium/efectos de los fármacos , Geotrichum/efectos de los fármacos , Penicillium/efectos de los fármacos , Tiocarbamatos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Derivados del Benceno/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Estereoisomerismo , Tiocarbamatos/síntesis química , Tiocarbamatos/químicaRESUMEN
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.
Asunto(s)
Aminas/química , Carbono/química , Hidrógeno/química , Alquenos/química , Compuestos de Anilina/química , Bencilaminas/química , Diseño de Fármacos , Quinolinas/químicaRESUMEN
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.
RESUMEN
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.
RESUMEN
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.
Asunto(s)
Antifúngicos/farmacología , Hongos/efectos de los fármacos , Furanos/farmacología , Pirazoles/farmacología , Antifúngicos/síntesis química , Pared Celular/efectos de los fármacos , Furanos/síntesis química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Pirazoles/síntesis química , Relación Estructura-ActividadRESUMEN
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.
RESUMEN
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.
Asunto(s)
Indoles/química , Microondas , Catálisis , Ciclización , Estructura MolecularRESUMEN
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.
Asunto(s)
Ácidos Carboxílicos/química , Cobre/química , Tiazinas/síntesis química , Tiazoles/química , Catálisis , Espectroscopía de Resonancia Magnética , Estructura Molecular , Solventes/química , TemperaturaRESUMEN
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.
RESUMEN
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.
Asunto(s)
Cromanos/química , Cicloheptanos/química , Indoles/química , Ácidos de Lewis/química , Mesilatos/química , Catálisis , Estructura MolecularRESUMEN
We herein report the development of a novel Pd/Ni dual-catalyzed ring-opening functionalization of gem-difluorinated cyclopropanes (gem-F2CPs) with azaaryl acetates. This bimetallic catalytic strategy streamlines the diversity-oriented synthesis (DOS) of α-quaternary 2-fluoroallylic azaaryl acetates with features of a broad scope and excellent functional group tolerance, which enables the efficient late-stage transformation of natural product-derived gem-F2CPs. The resulting α-quaternary azaaryl acetates could serve as a valuable platform to prepare other different fluoroallylic azaaryl scaffolds.
RESUMEN
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+).
Asunto(s)
Aminas/química , Indoles/química , Indoles/síntesis química , Cetonas/síntesis química , Compuestos Organometálicos/química , Paladio/química , Acilación , Catálisis , Cetonas/química , Estructura Molecular , Oxidación-ReducciónRESUMEN
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.
Asunto(s)
Bromobencenos/química , Cobre/química , Indoles/química , Indoles/síntesis química , Isoquinolinas/química , Isoquinolinas/síntesis química , Paladio/química , Pirroles/química , Pirroles/síntesis química , Catálisis , Estructura MolecularRESUMEN
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.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Proteómica , Antibacterianos/farmacologíaRESUMEN
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.
Asunto(s)
Norbornanos , Paladio , CatálisisRESUMEN
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.
RESUMEN
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.
Asunto(s)
Benzaldehídos/química , Bencimidazoles/síntesis química , Yodo/química , Isoquinolinas/síntesis química , Bencimidazoles/química , Ciclización , Isoquinolinas/química , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
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.
Asunto(s)
Benceno/química , Compuestos Organometálicos/química , Sulfuros/química , Tiofenos/síntesis química , Catálisis , Cromatografía en Capa Delgada , Cromatografía de Gases y Espectrometría de Masas , Espectroscopía de Resonancia Magnética , Espectrofotometría InfrarrojaRESUMEN
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.
RESUMEN
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.