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1.
J Org Chem ; 89(5): 2984-2995, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38334453

RESUMO

Rh(III)-catalyzed C7-alkylation of isatogens (indolin-3-one N-oxides) with malonic acid diazoesters has been developed. This strategy utilizes oxygen anion on the N-oxide group of isatogens as a directing group and successfully achieves the synthesis of a series of C7-alkylated isatogens with moderate to good yields (48-86% yields). Moreover, the N-oxides of isatogens can not only serve as the simple directing group for C7-H bond cleavage but also be deoxidized for easy removal.

2.
J Org Chem ; 88(6): 3927-3934, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36815756

RESUMO

Herein, a protecting-group-free protocol was developed to realize a time and step economy diversification of the Meridianin alkaloid. A broad range of substituents are tolerated to deliver the products in moderate to high yields, and the first synthesis of Meridianin B was achieved. The simplicity of this protocol enables the rapid construction of a Meridianin derivative library for antibiofilm evaluation. Preliminary results reveal that Meridianin derivatives were capable of inhibiting the Acinetobacter baumannii biofilm and lowering the antibiotic MIC synergistically.


Assuntos
Acinetobacter baumannii , Alcaloides , Antineoplásicos , Antibacterianos/farmacologia , Biofilmes , Testes de Sensibilidade Microbiana
3.
J Org Chem ; 88(22): 15589-15596, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37931324

RESUMO

The 4-aminoquinoline moiety is widely present in various bioactive compounds and marketed drugs, while the preparation of this target structure relies heavily on the amination of 4-chloroquinolines. Herein, an atom and step economic procedure was developed based on an aerobic dehydrogenative aromatization strategy. Unlike the well-known palladium-catalyzed dehydrogenative aromatization of cyclohexanones with amines, synergistic Pd/Cu catalysis is crucial for 2,3-dihydroquinolin-4(1H)-one type of substrates. Under the optimized conditions, a range of aromatic/aliphatic amines and 2,3-dihydroquinolin-4(1H)-ones were coupled to give the corresponding 4-aminoquinoline products in moderate to high yields, and the application of the current methodology for the preparation and late-stage diversification of marketed drugs was also demonstrated.

4.
J Org Chem ; 87(24): 16492-16505, 2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36473149

RESUMO

A convenient method was developed for the preparation of thiolated compounds via a DBU-catalyzed aerobic cross-dehydrogenative coupling (CDC) reaction. The established protocol is environmentally friendly and operationally simple. Substrates like (hetero)aryl acetates, (hetero)aryl ketones, and indoles could be transformed into the corresponding thiolated products in moderate to high yields and further applied in the preparation of bioactive compounds in a prefunctionalization-free manner.


Assuntos
Cetonas , Compostos de Sulfidrila , Catálise , Estrutura Molecular , Cetonas/química
5.
Org Biomol Chem ; 20(32): 6423-6431, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35880643

RESUMO

An efficient radical annulation of N-arylacrylamides with disulfides is developed for the synthesis of sulfurated oxindoles. The reaction occurs in a facile manner using CoBr2 as both an initiator and a promoter for the first time and (NH4)2S2O8 as the oxidant. By controlling the CoBr2/(NH4)2S2O8 ratio, a wide range of sulfurated and brominated/sulfurated oxindoles are selectively prepared in good to excellent yields. The present protocol is simple and highly atom economical, and can tolerate a broad range of substrates.


Assuntos
Cobalto , Dissulfetos , Indóis , Oxindóis
6.
Bioorg Med Chem ; 76: 117095, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36442439

RESUMO

The overuse of antibiotics will led to the increase of drug resistance. Especially, the multidrug-resistant A. baumannii became the leading cause of nosocomial infections with high rates of morbimortality. The drug resistance of A. baumannii is greatly attributed to its biofilm. To alleviate the burden of drug resistance, the anti-virulence signaling strategies was developed. By specifically interfering with the ability of the bacteria to recognize host signals that are needed to establish infection, the bacteria are less able to colonize the host. In this paper, 39 N-acyl-2-aminopyrimidine derivatives were synthesized and tested for their biofilm inhibition efficacy. The screening results reveal that some of the analogues (3ac, 8d) efficiently inhibited the biofilm formation of A. baumannii (IC50 as low as 3.8 µM), and the biofilm inhibition ability was further demonstrated with laser confocal results and extracellular polysaccharides inhibition test. Further motility test reveals our compounds are quorum sensing inhibitors. Besides, the synergistic effect of compounds 3ac and 8d with different antibiotics suggest its potential clinical significance, which was further enhanced by the long time biofilm inhibition test after coating with PLGA. Finally, we also look into the safety of the compounds with cytotoxicity assay.


Assuntos
Acinetobacter baumannii
7.
J Org Chem ; 86(13): 8620-8629, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34097828

RESUMO

An efficient aerobic iron-catalyzed annulation of unsaturated carboxylic acids with disulfides has been developed. This procedure proceeds using FeCl3 as the catalyst and KI as an iodine source under an air atmosphere, which provides practical access to a wide range of substituted γ-lactone derivatives. The disclosed method is quite simple, highly atom-economic, environmentally friendly, and tolerates a broad substrate scope.


Assuntos
Ferro , Lactonas , Ácidos Carboxílicos , Catálise , Dissulfetos
8.
Org Biomol Chem ; 18(24): 4551-4555, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32484497

RESUMO

A highly enantioselective allylic alkylation of isoquinolinedione derivatives under palladium catalysis was developed in the preparation of quaternary carbon stereocenters. Under standard reaction conditions, excellent yields and enantioselectivities were realized and the products could be transformed into dihydroisoquinolone with vicinal chiral carbon centers or THIQ core structures in short steps with high yields.

9.
Bioorg Med Chem ; 28(16): 115606, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32690261

RESUMO

The emergence of multidrug resistant microorganisms has triggered the impending need for new aitimicrobial strategies. The antivirulence strategy with the benefite of alleviating the drug resistance becomes the focus of research. In this study, 22 quorum sensing inhibitors were synthesized by mimicking the structure of autoinducer and acinetobactin and up to 34% biofilm inhibition was observed with 5u. The biofilm inhibition effect was further demonstrated with extracellular polysaccharides inhibition and synergism with Gentamycin sulphate.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Quinazolinonas/química , Quinazolinonas/farmacologia , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/fisiologia , Antibacterianos/síntese química , Humanos , Quinazolinonas/síntese química
10.
J Org Chem ; 84(12): 8168-8176, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31192597

RESUMO

An organocatalytic asymmetric α-sulfenylation of 2-substituted indolin-3-ones with N-(alkylthio or arylthio)succinimides has been developed for the first time using Cinchona-derived squaramide as the catalyst. Various chiral 2,2-disubstituted indole-3-ones with S- and N-containing heteroquaternary carbon stereocenters were obtained with up to 98% yield and 99% ee.

11.
RSC Adv ; 12(38): 25068-25080, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36199871

RESUMO

Multi-drug-resistant microbial pathogens are a serious global health problem. New compounds with antibacterial activity serve as good candidates for developing novel antibacterial drugs which is very urgent and important. In this work, based on the unique scaffold of indirubin, an active ingredient of traditional Chinese medicine formulation Danggui Luhui Wan, we synthesized 29 indirubin-3'-monoximes and preliminarily evaluated their antibacterial activities. The antibacterial activity results demonstrated that the synthesized indirubin-3'-monoximes 5a-5z and 5aa-5ad displayed good potency against S. aureus ATCC25923 (MIC = 0.4-25.6 µg mL-1). Among them, we found that the 5-F, 5-Cl and 7-CF3 substituted indirubin-3'-monoximes 5r, 5s and 5aa also showed better antibacterial efficiency for S. aureus (MICs up to 0.4 µg mL-1) than the prototype natural product indirubin (MIC = 32 µg mL-1). More importantly, indirubin-3'-monoxime 5aa has certain synergistic effect with levofloxacin against clinic multidrug-resistant S. aureus (fractional inhibitory concentration index: 0.375). In addition, relevant experiments including electron microscopy observations, PI staining and the leakage of extracellular potassium ions and nucleic acid (260 nm) have been performed after treating S. aureus with indirubin-3'-monoxime 5aa, and the results revealed that indirubin-3'-monoximes could increase the cell membrane permeability of S. aureus. Although indirubin-3'-monoxime 5aa showed some cytotoxicity toward SH-SY5Y cells relative to compounds 5r and 5s, the skin irritation test of male mice after shaving showed that compound 5aa at a concentration of 12.8 µg mL-1 had no toxicity to mouse skin, and it could be used as a leading compound for skin antibacterial drugs.

12.
RSC Adv ; 10(70): 42912-42915, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-35514906

RESUMO

A mild and efficient enantioselective amination of 4-alkylisoquinoline-1,3(2H,4H)-dione derivatives was established, which is compatible with a broad range of substrates and delivers the final products in excellent yields (up to 99%) and ee values (up to 99%) with low catalyst loading (down to 1 mol%). The synthetic potential of this methodology was also demonstrated in the gram scale level.

13.
Org Lett ; 21(7): 2236-2240, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30859824

RESUMO

A novel and efficient cascade method has been developed for the diastereoselective preparation of trifluoromethyl-containing dihydrooxazoles in high yields. The reaction was applicable to electron-deficient, electron-rich arenes, heteroarenes, and alkyl groups. Control experiments were conducted to explore the reaction mechanism and reveal that the byproduct formed in situ is the catalyst for this reaction and a tether derived from trifluoropyruvate is a key intermediate for this reaction.

14.
RSC Adv ; 8(45): 25292-25297, 2018 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35539771

RESUMO

A novel and efficient method for the synthesis of nucleophilic 2-monoarylated indole-3-ones via palladium-catalyzed direct C(sp3)-H arylation of indole-3-ones with aryl halides has been developed. Various 2-monoarylated indole-3-ones were readily obtained with yields up to 95%. As a class of important nucleophilic intermediates, 2-monoarylated indole-3-ones can be used for the construction of C2-quaternary indolin-3-one skeletons.

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