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2.
MMW Fortschr Med ; 165(2): 26, 2023 02.
Artigo em Alemão | MEDLINE | ID: mdl-36703052

Assuntos
Lactamas , Nitrilas , Humanos
3.
Artigo em Inglês | MEDLINE | ID: mdl-36700602

RESUMO

BACKGROUND: The spread of carbapenemase- and extended-spectrum ß-lactamase (ESBL)-producing gram-negative bacilli (GNB) represent a global public health threat that limits therapeutic options for hospitalized patients. This study aimed to evaluate the in-vitro susceptibility of ß-lactam-resistant GNB to ceftazidime-avibactam (C/A) and ceftolozane-tazobactam (C/T), and investigate the molecular determinants of resistance. METHODS: Overall, 101 clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected from a general hospital in Brazil were analyzed. Susceptibility to the antimicrobial agents was evaluated using an automated method, and the minimum inhibitory concentrations (MIC50/90) of C/A and C/T were determined using Etest®. The ß-lactamase-encoding genes were investigated using polymerase chain reaction. RESULTS: High susceptibility to C/A and C/T was observed among ESBL-producing Enterobacterales (100% and 97.3% for CLSI and 83.8% for BRCAST, respectively) and carbapenem-resistant P. aeruginosa (92.3% and 87.2%, respectively). Carbapenemase-producing Klebsiella pneumoniae exhibited high resistance to C/T (80%- CLSI or 100%- BRCAST) but high susceptibility to C/A (93.4%). All carbapenem-resistant K. pneumoniae isolates were susceptible to C/A, whereas only one isolate was susceptible to C/T. Both antimicrobials were inactive against metallo-ß-lactamase-producing K. pneumoniae isolates. Resistance genes were concomitantly identified in 44 (44.9%) isolates, with bla CTX-M and bla SHV being the most common. CONCLUSIONS: C/A and C/T were active against microorganisms with ß-lactam-resistant phenotypes, except when resistance was mediated by metallo-ß-lactamases. Most C/A- and C/T-resistant isolates concomitantly carried two or more ß-lactamase-encoding genes (62.5% and 77.4%, respectively).


Assuntos
Antibacterianos , Lactamas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Brasil , Hospitais Gerais , Ceftazidima/farmacologia , Cefalosporinas/farmacologia , Tazobactam/farmacologia , Combinação de Medicamentos , Bactérias Gram-Negativas/genética , Pseudomonas aeruginosa , Klebsiella pneumoniae , Carbapenêmicos , beta-Lactamases/genética , Testes de Sensibilidade Microbiana
4.
Sci Rep ; 13(1): 137, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599900

RESUMO

The greening of analytical methods has gained interest in the quantitative analysis field to reduce environmental impact and improve safety health conditions for analysts. Nirmatrelvir plus ritonavir is a new FDA approved co-packaged medication developed for the treatment of COVID-19. The aim of this research was to develop green fitted HPLC method using pre experimental computational testing of different stationary phases as well as selecting mobile phase regarding to green analytical chemistry principles. Computational study was designed to test the physical interaction between nirmatrelvir and ritonavir and different columns (C8, C18, Cyano column). The study showed that the C18 column was better for simultaneous HPLC analysis of the cited drugs. Regarding to green point of view, mobile phase consisted of ethanol: water (80:20, v/v) provided an efficient chromatographic separation of nirmatrelvir and ritonavir within a short analytical run time, reasonable resolution and excellent sensitivity. Isocratic elution was performed on a selected C18 column and a green adjusted mobile phase at flow rate of 1 mL/min and UV detection at 215 nm. The chromatographic system allowed complete baseline separation with retention times of 4.9 min for nirmatrelvir and 6.8 min for ritonavir. The method succeeded to determine nirmatrelvir and ritonavir over the concentration range of 1.0-20.0 µg/mL in the pure form and in pharmaceutical dosage form. Greenness profiles of the applied HPLC method was assessed using analytical eco-scale, the green analytical procedure index and the AGREE evaluation method. The results revealed adherence of the described method to the green analytical chemistry principles. The authors hope to provide a promising challenge for achieving green goals through integrating computational tools and applying them with green assessment metrics.


Assuntos
COVID-19 , Ritonavir , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Lactamas , Preparações Farmacêuticas
5.
J Org Chem ; 88(2): 1185-1193, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36579612

RESUMO

The Ru-catalyzed intramolecular oxidative amidation (lactamization) of aromatic alkynylamines with 4-picoline N-oxide as an external oxidant has been developed. This chemoselective process is very efficient to achieve medium-sized ε- and ζ-lactams (seven- and eight-membered rings) but not for the formation of common δ-lactams (six-membered rings). DFT studies unveiled the capital role of the chain length between the amine and the alkyne functionalities: the longer the connector, the more favored the lactamization process vs hydroamination.


Assuntos
Aminas , Lactamas , Teoria da Densidade Funcional , Catálise , Estresse Oxidativo
8.
Sci Adv ; 8(51): eadd7197, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36542720

RESUMO

The oral protease inhibitor nirmatrelvir is of key importance for prevention of severe coronavirus disease 2019 (COVID-19). To facilitate resistance monitoring, we studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) escape from nirmatrelvir in cell culture. Resistant variants harbored combinations of substitutions in the SARS-CoV-2 main protease (Mpro). Reverse genetics revealed that E166V and L50F + E166V conferred high resistance in infectious culture, replicon, and Mpro systems. While L50F, E166V, and L50F + E166V decreased replication and Mpro activity, L50F and L50F + E166V variants had high fitness in the infectious system. Naturally occurring L50F compensated for fitness cost of E166V and promoted viral escape. Molecular dynamics simulations revealed that E166V and L50F + E166V weakened nirmatrelvir-Mpro binding. Polymerase inhibitor remdesivir and monoclonal antibody bebtelovimab retained activity against nirmatrelvir-resistant variants, and combination with nirmatrelvir enhanced treatment efficacy compared to individual compounds. These findings have implications for monitoring and ensuring treatments with efficacy against SARS-CoV-2 and emerging sarbecoviruses.


Assuntos
COVID-19 , Doenças Transmissíveis , Humanos , SARS-CoV-2/genética , Técnicas de Cultura de Células , Lactamas , Nitrilas
9.
Bioanalysis ; 14(20): 1305-1315, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36541270

RESUMO

Aim: A sensitive and selective method for the determination of nirmatrelvir in dried human blood collected by Tasso-M20 was developed and validated from 20.0 to 20,000 ng/ml. Materials & methods: Nirmatrelvir and its stable-labeled internal standard were isolated from approximately 20 µl of blood dried on one volumetric absorptive pad inside the Tasso-M20 device by extraction with methanol, followed by dilution of the supernatant. The extracts were analyzed by high-performance liquid chromatography coupled with tandem mass spectrometric detection. Results & conclusion: The method was fully validated. Hematocrit levels do not impact assay accuracy. Stabilities to cover sample drying and storage at a variety of conditions were conducted. The validated method was used in multiple clinical studies with excellent performance.


Assuntos
Teste em Amostras de Sangue Seco , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida/métodos , Teste em Amostras de Sangue Seco/métodos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Lactamas , Reprodutibilidade dos Testes
10.
Sci Rep ; 12(1): 21965, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36536009

RESUMO

The study's goal was to develop a spore-based paper strip biosensor for detecting ß-lactam antibiotics in milk using the enzyme induction principle. A new spore-based paper strip biosensor has been developed after important operating parameters such as spore volume, substrate volume, exposure time and temperature, and incubation time and temperature were optimised. The limit of detection for various ß-lactam antibiotics, including amoxicillin, penicillin, ampicillin, carbenicillin, cloxacillin, nafcillin, oxacillin, cephalothin, cefalexin, cefoxitin, cefazolin, and cefuroxime, was determined in milk with detection sensitivity of 1 ppb, 2 ppb, 2 ppb, 10 ppb, 10 ppb, 10 ppb, 20 ppb, 10 ppb 1000 ppb, 10 ppb 300 ppb and 100 ppb, respectively. It was also tested with other contaminants such non-ß-lactam antibiotics, pesticides, aflatoxin, heavy metals, and other chemical contaminants, and no interference was found, indicating that the created biosensor had a low rate of false positive and negative results. In comparison to the AOAC-approved CHARM-ROSA ß-lactam strip test, which identified 7 raw milk and zero pasteurised milk samples positive for ß-lactam antibiotics, the sensor was further analysed and verified using 200 raw milk and 105 pasteurised milk samples. This indicates a perfect match between our biosensor and the AOAC-approved CHARM-ROSA ß-lactam strip test. The developed spore-based paper strip biosensors are expected to be useful in the rapid and cost-effective detection of ß-lactam antibiotic residues in milk samples at the dairy farm, reception dock, and production units, respectively.


Assuntos
Lactamas , beta-Lactamas , Animais , Leite/química , Antibacterianos/análise , Monobactamas , Esporos/química
11.
J Org Chem ; 87(23): 16090-16098, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36370090

RESUMO

We report herein a facile strategy to synthesize trifluoromethylated γ-lactams through trifluoromethylcarbonylation of N-cyano alkenes using readily available CF3SO2Na as the CF3 radical source. A range of trifluoromethyl-containing γ-lactams was obtained in good yields. This transition-metal-free protocol is demonstrated with mild conditions, broad substrate scope, good functional group tolerance, convenient reagents, and an easy-to-handle operating system.


Assuntos
Alcenos , Lactamas , Indicadores e Reagentes , Metilação , Íons
12.
J Org Chem ; 87(22): 15634-15643, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36322913

RESUMO

The natural product armeniaspirol possesses a unique spirocyclic N,O-ketal in an α,ß-dichloro-α,ß-unsaturated lactam scaffold that has proved challenging to synthesize. Herein, we characterize the oxidative chlorination of pyrrole-2-carboxylate derivatives that rapidly generates this scaffold. The scope of this oxidation was extended to a series of esters and amides. Pyrrole-2-ketones could not be converted into the lactam due to an oxidative fragmentation. This result was unexpected since chloro-armeniaspirol has been synthesized via oxidative chlorination of a pyrrole-2-ketone. Examination of this successful oxidation showed that the desired scaffold was accessed due to intramolecular trapping from the neighboring free phenol, preventing fragmentation. Using the product of methyl N-methyl pyrrole-2-carboxylate oxidation 7b, we attempted to access the natural product armeniaspirol 2; however, an unanticipated Lewis acid-mediated rearrangement led to formation of a constitutional isomer, pseudoarmeniaspirol A 1. A small panel of pseudoarmeniaspirol analogues was synthesized and evaluated for antibiotic activity, inhibition of the targets of armeniaspirol, ClpXP and ClpYQ, and protonophore activity. While pseudoarmeniaspirol shows antibiotic activity, it does not target ClpXP or ClpYQ and has less protonophore activity than the natural product.


Assuntos
Produtos Biológicos , Ácidos de Lewis , Pirróis , Cetonas , Antibacterianos , Lactamas
13.
Molecules ; 27(22)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36431796

RESUMO

One of the goals of diversity-oriented synthesis is to achieve the structural diversity of obtained compounds. As most biologically active compounds are chiral, it is important to develop enantioselective methods of their synthesis. The application of kinetic resolution in DOS is problematic because of low efficiency (max. 50% yield) and many purification steps. The further derivatization of kinetic resolution products in DOS leads to the formation of a narrow library of compounds of the same stereochemistry. To overcome these limitations, we present a new concept in which the kinetic resolution is combined, the subsequent reaction of which in a one-pot protocol leads to the simultaneous formation of two skeletally and enantiomerically diverse platform molecules for DOS. Their further derivatization can gain access to a double-sized library of products in respect to a classical approach. The validity of our concept was evidenced in enzymatic kinetic resolution followed by a ring-closing metathesis cascade. From racemic carboxylic acid ester, a simultaneous formation of enantiopure lactones and lactams was achieved. These compounds are important building blocks in organic and medicinal chemistry and until now were synthesized in separate procedures.


Assuntos
Lactamas , Lactonas , Lactamas/química , Lactonas/química , Cinética , Ciclização
14.
J Crit Care ; 72: 154172, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36270240

RESUMO

INTRODUCTION: The average body weight is smaller in Asian patients compared with Western patients, but influence of body weight in antibiotic dosing is unknown. This study was to predict the optimal ceftazidime, cefepime, meropenem, piperacillin/tazobactam doses in Asian patients undergoing continuous venovenous hemofiltration (CVVH). METHODS: Monte Carlo simulations (MCS) were performed using published Asian demographics and pharmacokinetics parameters in 5000 virtual patients at three CVVH effluent rates (Qeff; 20, 30, 40 mL/kg/h). Various dosing regimens were assessed for the probability of target attainments using 60% fT > 1 × MIC or 4xMIC and neurotoxicity risk at 48-h using suggested neurotoxicity thresholds. RESULTS: Ceftazidime 1 g q12h, meropenem 1 g q12h, and piperacillin/tazobactam 3.375 g q6h were optimal for all Qeff settings against fT > 1 × MIC. Cefepime 2 g q24h and 2 g q12h were optimal at 20 and 30-40 mL/kg/h respectively. For the aggressive PD target (4 × MIC), optimal ceftazidime regimens were 1.25 g q8h (20-30 mL/kg/h) and 1.5 g q8h (40 mL/kg/h). Cefepime 2 g q8h and meropenem 1 g q8h were optimal at all Qeff settings. No simulated piperacillin doses attained the aggressive PD target. Increased neurotoxicity risk was predicted with ceftazidime and cefepime doses attaining the efficacy. CONCLUSION: MCS enabled the prediction of optimal ß-lactam dosing regimens for Asian patients receiving CVVH at varying Qeff. Clinical validation is warranted.


Assuntos
Ceftazidima , Estado Terminal , Humanos , Cefepima , Meropeném , Testes de Sensibilidade Microbiana , Lactamas , Antibacterianos/uso terapêutico , Piperacilina , Combinação Piperacilina e Tazobactam , Peso Corporal
15.
Arch Razi Inst ; 77(2): 669-673, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-36284979

RESUMO

Antimicrobial resistance is becoming an arising global issue. Until recent years, more than 50% of commercially available antibiotics were ß-lactam. Pathogenic bacteria which are resistant to antibiotics include all ß-lactams except for cephamycin and carbapenems. This study aimed to evaluate some ß-lactams and carbapenems antimicrobials resistance in Klebsiella oxytoca. In total, 177 urinary tract infection samples were collected for the purposes of the study. Isolates were identified using morphological features and routine biochemical testing. All isolates were tested for susceptibility to 11 antibiotics using the usual disc diffusion method. The result showed that 155 (87.57%) and 20 (11.29%) out of 177 collected urine samples were gram-negative bacterial isolates and gram-positive bacterial isolates, respectively. The findings also showed that there were two samples (1.12 %) with no growth. The results proved no susceptibility to Ampicillin, Cloxacillin, Ceftazidime, Penicillin, Piperacillin with a resistance rate of 100%.


Assuntos
Cefamicinas , Infecções Urinárias , Animais , Carbapenêmicos/farmacologia , Klebsiella oxytoca , Ceftazidima , Lactamas , beta-Lactamases , Iraque , Testes de Sensibilidade Microbiana/veterinária , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/veterinária , Infecções Urinárias/microbiologia , Piperacilina , Antibacterianos/farmacologia , Cloxacilina
16.
Molecules ; 27(19)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36234688

RESUMO

The NIS synthetase family of enzymes responsible for the biosynthesis of siderophores is increasingly associated with bacterial virulence. Proteins in this class represent outstanding potential drug targets, assuming that basic biochemical and structural characterizations can be completed. Towards this goal, we have mated an improved synthesis of the non-commercial amino acid N-hydroxy-N-succinylcadaverine (HSC, 6) with an isothermal titration calorimetry (ITC) assay that profiles the iterative stages of HSC trimerization and macrocyclization by NIS synthetase DesD from Streptomyces coelicolor. HSC synthesis begins with multigram-scale Gabrielle and tert-butyl N-(benzyloxy)carbamate alkylations of 1-bromo-5-chloropentane following prior literature, but the end-game reported herein has two advantages for greater material throughput: (1) hydrogenolysis of benzyl ether and Cbz blocking groups is best accomplished with Pearlman's catalyst at 40 psi of H2 and (2) purification of neutral (zwitterionic) HSC is effected by simple flash chromatography over silica gel in MeOH. HSC is subsequently shown to be a substrate for NIS synthetase DesD, which catalyzes three successive amide bond syntheses via adenyl monophosphate ester intermediates. We quantify and present the iterative and overall enzyme kinetic constants associated with formation of the cyclotrimeric siderophore desferrioxamine E (dfoE, 1).


Assuntos
Produtos Biológicos , Sideróforos , Amidas , Aminoácidos , Carbamatos , Ésteres , Éteres , Ácidos Hidroxâmicos , Lactamas , Ligases , Sideróforos/química , Sílica Gel
17.
Molecules ; 27(19)2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36235117

RESUMO

The protein HFE (homeostatic iron regulator) is a key regulator of iron metabolism, and mutations in HFE underlie the most frequent form of hereditary haemochromatosis (HH-type I). Studies have shown that HFE interacts with transferrin receptor 1 (TFR1), a homodimeric type II transmembrane glycoprotein that is responsible for the cellular uptake of iron via iron-loaded transferrin (holo-transferrin) binding. It has been hypothesised that the HFE/TFR1 interaction serves as a sensor to the level of iron-loaded transferrin in circulation by means of a competition mechanism between HFE and iron-loaded transferrin association with TFR1. To investigate this, a series of peptides based on the helical binding interface between HFE and TFR1 were generated and shown to significantly interfere with the HFE/TFR1 interaction in an in vitro proximity ligation assay. The helical conformation of one of these peptides, corresponding to the α1 and α2 helices of HFE, was stabilised by the introduction of sidechain lactam "staples", but this did not result in an increase in the ability of the peptide to disrupt the HFE/TFR1 interaction. These peptides inhibitors of the protein-protein interaction between HFE and TFR1 are potentially useful tools for the analysis of the functional role of HFE in the regulation of hepcidin expression.


Assuntos
Hemocromatose , Hepcidinas , Hemocromatose/genética , Hemocromatose/metabolismo , Proteína da Hemocromatose/genética , Proteína da Hemocromatose/metabolismo , Hepcidinas/metabolismo , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Ferro/metabolismo , Lactamas , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Peptídeos/metabolismo , Peptídeos/farmacologia , Receptores da Transferrina/metabolismo , Transferrina/metabolismo
18.
Molecules ; 27(19)2022 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-36235245

RESUMO

Many heterocyclic compounds can be synthetized using diaza-1,3-butadienes (DADs) as key structural precursors. Isolated and in situ diaza-1,3-butadienes, produced from their respective precursors (typically imines and hydrazones) under a variety of conditions, can both react with a wide range of substrates in many kinds of reactions. Most of these reactions discussed here include nucleophilic additions, Michael-type reactions, cycloadditions, Diels-Alder, inverse electron demand Diels-Alder, and aza-Diels-Alder reactions. This review focuses on the reports during the last 10 years employing 1,2-diaza-, 1,3-diaza-, 2,3-diaza-, and 1,4-diaza-1,3-butadienes as intermediates to synthesize heterocycles such as indole, pyrazole, 1,2,3-triazole, imidazoline, pyrimidinone, pyrazoline, -lactam, and imidazolidine, among others. Fused heterocycles, such as quinazoline, isoquinoline, and dihydroquinoxaline derivatives, are also included in the review.


Assuntos
Imidazolidinas , Imidazolinas , Butadienos/química , Hidrazonas , Iminas/química , Indóis , Isoquinolinas , Lactamas , Pirazóis , Pirimidinonas , Quinazolinas , Triazóis
19.
Front Public Health ; 10: 985834, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211665

RESUMO

Objective: Six anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs), including one domestic (ensartinib) and five imported ALK-TKIs (crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib), have been recommended as first-line treatments for advanced ALK-positive NSCLC in China. This study sought to examine the cost-effectiveness of these six novel therapies in Chinese patients. Material and methods: We constructed a Markov model to compare the cost-effectiveness of the six ALK-TKIs as a first-line treatment for patients with advanced ALK-positive NSCLC from the perspective of the Chinese healthcare system. Transition probabilities were estimated by synthesizing data from the PROFILE 1,029 trial and a network meta-analysis. Health state utilities and costs were sourced from published literature, publicly available national databases, and local general hospitals. The robustness of model was assessed via deterministic sensitivity analyses and probabilistic sensitivity analyses. Results: Compared with crizotinib, ensartinib achieved additional 0.12 quality-adjusted life-year (QALY) with marginal costs of $3,249, resulting in an incremental cost-effectiveness ratio (ICER) of $27,553/ QALY. When compared with ceritinib and brigatinib, ensartinib achieved additional 0.06 and 0.03 QALYs with substantially reduced costs. When compared with lorlatinib and alectinib, ensartinib was associated with a lower QALY and decreased total costs; the ICERs for lorlatinib and alectinib were $934,101/ QALY and $164,888/ QALY, respectively. Conclusion: For Chinese patients with advanced ALK-positive NSCLC, ensartinib was a cost-effective option compared with crizotinib, and was a dominant alternative to ceritinib and brigatinib. Although lorlatinib and alectinib were associated with prolonged survival compared with ensartinib, they were less cost-effective than ensartinib due to the overwhelming total costs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Aminopiridinas , Quinase do Linfoma Anaplásico/análise , Carbazóis , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios Clínicos como Assunto , Análise Custo-Benefício , Crizotinibe , Humanos , Lactamas , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Metanálise em Rede , Compostos Organofosforados , Piperazinas , Piperidinas , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis , Piridazinas , Pirimidinas , Sulfonas
20.
Nat Commun ; 13(1): 5964, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-36216794

RESUMO

Nitrogen-based heterocycles have aroused widespread interest due to their reoccurrence in many pharmaceuticals. Amongst these motifs, the enantioenriched lactams are the ubiquitous scaffolds found in myriad biologically active natural products and drugs. Recently, the transition metal-catalyzed asymmetric carbamoylation has been widely employed as a straightforward arsenal for chiral lactam architecture synthesis, including ß-lactam and γ-lactam. However, despite the extensive efforts, there still remains no protocol to accomplish the related δ-lactam synthesis. In this manuscript, the Ni-catalyzed enantioselective carbamoylation of unactivated alkenes by the leverage of reductive dicarbofunctionalization strategy allows for the expedient access to two types of mostly common six-membered lactams: 3,4-dihydroquinolinones and 2-piperidinone in high yield and enantioselectivity. This protocol features with good functional group tolerance, as well as broad substrate scope. The newly developed chiral 8-Quinox skeleton ligand is the key parameter for this transformation, which significantly enhances the reactivity and enantioselectivity.


Assuntos
Alcenos , Produtos Biológicos , Catálise , Lactamas , Ligantes , Estrutura Molecular , Nitrogênio , Preparações Farmacêuticas , Carbamilação de Proteínas , Estereoisomerismo , beta-Lactamas
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