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We developed performant in situ hypohalite, especially hypobromite, catalysis for the oxidative dearomatization of low-reactivity electron-deficient arenols. The reaction scope encompasses inter- and intramolecular oxidative dearomative C-O, C-N, and C-C coupling reactions. Notably, using a chiral ammonium countercation, we achieved enantioselective hypobromite catalysis for oxidative dearomative coupling reactions. Mechanistic studies revealed that the reaction mechanisms might differ depending on the halide identity.
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Background: Bloodstream infections are a serious public health problem that requires follow-up with blood culture; this negatively affects the course of the disease and patient healthcare costs in patients with malignancy. This study aimed to determine the growth frequency of pathogens and their antibiotic resistance profiles in the blood cultures of patients with hematological and oncogenic malignancies. Materials and methods: The results of 7451 blood cultures, obtained from 2926 patients between January 2017 and January 2022, were evaluated retrospectively. Of these cultures, 3969 were obtained from patients with malignancy (diagnostic codes C00-D48 in ICD-10) and 3482 from patients without malignancy. The hospital information management system modules were used to acquire patient data and blood culture results. Results: Various microorganisms grew in 10.1% of blood cultures. Of these organisms, 64.1% were isolated from cases of malignancy. Of the pathogens, 49.2% were gram-negative bacteria, 47.7% were gram-positive bacteria, and 3.1% were fungi. The most frequently isolated bacteria were methicillin-resistant coagulase-negative staphylococci (3.2%), Escherichia coli (2.3%), Klebsiella pneumoniae (1.0%), methicillin-sensitive coagulase-negative staphylococci (0.7%), and Staphylococcus aureus (0.6%). Pathogen positivity was highest in the patient cultures with urinary system cancer (23.9%), thyroid and other endocrine gland cancers (20.6%), female and male genital organ cancers (18.2%/16.9%), and digestive organ cancer (14.2%). Gram-negative bacteria to ampicillin, piperacillin, and sulfamethoxazole-trimethoprim and Gram-positive bacteria to penicillin, erythromycin, and sulfamethoxazole-trimethoprim were highly resistant. Combined resistance to imipenem and meropenem was observed in 25 Gram-negative bacteria. Twelve (48%) of the carbapenem-resistant bacteria were isolated from patients with lymphoid, hematopoietic, and related tissue malignant neoplasia. Conclusion: This study reported microorganisms and their antimicrobial resistance in the blood cultures of malignant patients, a special patient group. It pointed out that the antibiotic resistance of Staphylococcus, Klebsiella pneumoniae, and E. coli is high enough to cause problems in the treatment of patients with malignancy.
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Catalyst design has traditionally focused on rigid structural elements to prevent conformational flexibility. Ishihara's elegant design of conformationally flexible C2-symmetric iodoarenes, a new class of privileged organocatalysts, for the catalytic asymmetric dearomatization (CADA) of naphthols is a notable exception. Despite the widespread use of the Ishihara catalysts for CADAs, the reaction mechanism remains the subject of debate, and the mode of asymmetric induction has not been well established. Here, we report an in-depth computational investigation of three possible mechanisms in the literature. Our results, however, reveal that this reaction is best rationalized by a fourth mechanism called "proton-transfer-coupled-dearomatization (PTCD)", which is predicted to be strongly favored over other competing pathways. The PTCD mechanism is consistent with a control experiment and further validated by applying it to rationalize the enantioselectivities. Oxidation of the flexible I(I) catalyst to catalytic active I(III) species induces a defined C2-symmetric helical chiral environment with a delicate balance between flexibility and rigidity. A match/mismatch effect between the active catalyst and the substrate's helical shape in the dearomatization transition states was observed. The helical shape match allows the active catalyst to adapt its conformation to maximize attractive noncovalent interactions, including I(III)···O halogen bond, N-H···O hydrogen bond, and π···π stacking, to stabilize the favored transition state. A stereochemical model capable of rationalizing the effect of catalyst structural variation on the enantioselectivities is developed. The present study enriches our understanding of how flexible catalysts achieve high stereoinduction and may serve as an inspiration for the future exploration of conformational flexibility for new catalyst designs.
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We serendipitously found an unprecedented 5-to-7-membered ring expansion of 2-alkylspiroindolenines to azepinoindoles mediated by n-tetrabutylammonium fluoride. The starting materials can be easily prepared by the hypoiodite-catalyzed oxidative dearomative spirocyclization of indole derivatives. Mildly basic conditions and electron-deficient protecting groups for the amines were found to be crucial to promoting chemoselective reactions. Moreover, the ring expansion of aniline-derived spiroindolenines proceeds smoothly under much milder conditions using only a catalytic amount of cesium carbonate.
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Objective: Silent brain infarcts (SBI) are thromboembolic complications associated with cardiac surgery, diagnostic angiography, and percutaneous interventions. Serum neuron-specific enolase (NSE) is the proven biomarker for measuring neuronal damage. This study aimed to evaluate the incidence of SBI, defined as elevated NSE after coronary chronic total occlusion (CTO) intervention and elective coronary stenting. Design: The study population consisted of two patient groups: the CTO group included consecutive patients with coronary CTO intervention, and the control group consisted of patients who underwent elective coronary intervention. NSE blood levels were measured before and 12-18 h after the procedure. NSE blood levels of >20 ng/mL were considered SBI. Results: A total of 108 patients were included in the study. Of these, 55 (50.9%) had SBI after the procedure. The SBI rate was 59.7% in the CTO group and 39.1% in the control group. Patients with SBI were more likely to have diabetes mellitus, hyperlipidemia, higher HbA1c, higher total stent length, and longer procedural time. Multivariate logistic regression analysis showed that CTO procedure (odds ratio [OR]: 3.129; 95% confidence interval [CI]: 1.246-7.858; p < 0.015) and diabetes mellitus (OR: 2.93; 95% CI: 1.185-7.291; p < 0.020) are independent predictors of SBI. Conclusion: Our data suggest that SBI occurs more frequently after CTO intervention than after non-CTO intervention. Intervention complexity and patient clinical characteristics may explain the increased incidence.
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Lesões Encefálicas , Oclusão Coronária , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/terapia , Vasos Coronários , CoraçãoRESUMO
Here we report the oxidative umpolung of 2,3-disubstituted indoles toward enantioselective dearomative aza-spirocyclization to give the corresponding spiroindolenines using chiral quaternary ammonium hypoiodite catalysis. Mechanistic studies revealed the umpolung reactivity of C3 of indoles by iodination of the indole nitrogen atom. Moreover, the introduction of pyrazole as an electron-withdrawing auxiliary group at C2 suppressed a competitive dissociative racemic pathway, and enantioselective spirocyclization proceeded to give not only spiropyrrolidines but also four-membered spiroazetidines that are otherwise difficult to access.
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Indóis , Estresse Oxidativo , Catálise , Compostos de Iodo , EstereoisomerismoRESUMO
We report the hypoiodite-catalyzed oxidative C-C homocoupling of arenols to biarenols or biquinones using aqueous hydrogen peroxide as an oxidant. In addition, by combining hypoiodite catalysis and lipophilic Lewis acid-assisted Brønsted acid catalysis under aqueous conditions, we achieved a tandem oxidation/cross-coupling reaction of hydroquinones with electron-rich arenes. These results highlight the substantial scope of hypoiodite/acid co-catalysis for use in oxidative coupling reactions.
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BACKGROUND: Brucellosis is a worldwide zoonotic disease that causes serious public health problems. This study aimed to identify Brucella strains isolated from various clinical samples by conventional and molecular methods and to determine antimicrobial susceptibilities against doxycycline (DOX), streptomycin (STR), ciprofloxacin (CIP) and rifampicin (RIF) by the gradient strip (E test) test method. METHODS: A total of 87 Brucella strains isolated from various clinical specimens between 2004 and 2018 were included in this study. While four of the 87 strains included in the study were identified only at the genus level, the remaining 83 strains were identified at the species level by the Real-Time Multiplex PCR (M-RT-PCR) method and conventional methods were used for biotyping. RESULTS: According to molecular identification results, 83 strains were identified as B. melitensis by the M-RT-PCR method, with 82 strains identified as Brucella melitensis biovar (bv) 3 and one as B. melitensis bv 1 according to the conventional biotyping method. Among the antibiotics studied, CIP was found to be the most active agent according to the minimum inhibitory concentrations (MIC)90 values. This was followed by DOX and STR, respectively. While all of the isolates were sensitive to CIP, DOX and STR, 18 (20.7%) strains were found to be moderately susceptible to RIF, with the highest values of MIC50 and MIC90. CONCLUSIONS: In our study, all strains were identified as B. melitensis. DOX, STR, CIP and RIF used in the treatment of brucellosis were found to be effective.
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Antibacterianos/farmacologia , Brucella/efeitos dos fármacos , Brucelose/tratamento farmacológico , DNA Bacteriano/análise , Brucella/genética , Brucelose/epidemiologia , Brucelose/microbiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Turquia/epidemiologiaRESUMO
The basic components of energy drinks include caffeine, guarana, taurine, ginseng, and sugar. The excessive consumption of energy drinks has been associated with cardiovascular events such as tachycardia and myocardial infarction in the literature. We herein describe a 24-year-old man admitted to the emergency department. The patient's medical history and family history were unremarkable. It was, however, learned that he had consumed 8 to 10 cans of energy drinks per day (3.5-4 Lit/d) in the 2-week period leading to the hospital admission. Physical examination revealed bilateral diffuse rales and 2+ pretibial edema. Echocardiography showed a left ventricular ejection fraction of 25% with global left ventricular hypokinesia and dilated left ventricular dimensions. Coronary angiography demonstrated normal coronary arteries. On cardiac magnetic resonance imaging, the left ventricle was dilated, and the systolic function was reduced. No pathological enhancement was observed. This case report and many previous studies support a possible link between caffeinated energy drinks and cardiovascular events.
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We developed the hypoiodite-catalyzed tandem dearomative peroxycyclization of homotryptamine derivatives to peroxytetrahydropyridoindolenines under mild conditions. During the course of a mechanistic study, we found that a tandem oxidative cyclization/epoxidation as an unexpected reaction proceeded in the presence of TEMPO as an additive. Intramolecular oxidative aminocyclization of homotryptamines at the C-2 position would give tetrahydropyridoindole, a common intermediate for both reactions. Control experiments suggested that while oxidative coupling with TBHP at the C-3 position might afford peroxyindolenines, a preferential electrophilic addition of TEMPO+, which might be generated in situ by the hypoiodite-catalyzed oxidation of TEMPO, at C-3 position followed by elimination and epoxidation might give epoxyindolenines. This serendipitous finding prompted us to develop a chemoselective divergent synthesis of peroxy- and epoxyindolenines by simple modification of the reaction conditions.
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OBJECTIVE: Crimean-Congo hemorrhagic fever (CCHF) is an acute and highly fatal disease. In this study, our aim was to compare and evaluate the prevalence of CCHF virus (CCHFV) antibody among occupational high-risk groups by using the enzyme-linked immunosorbent assay and draw attention to the occupational groups that are at high risk for CCHF infection in an endemic region for this zoonotic infection in Erzurum, Turkey. MATERIALS AND METHODS: The antibody levels against CCHFV were surveyed among slaughterhouse workers, animal breeders, and veterinarians. The study population was composed of 72 participants having direct contact with animals and 19 blood donors who were not in direct contact with animals. RESULTS: The overall rate of CCHF immunoglobulin G positivity in risk groups was found to be 6.94% (5/72). CCHFV antibodies were found in 4 (12.5%) individuals of the animal breeder group. This ratio was considered significantly higher compared with the healthy control group. CCHFV antibodies were found in only one person (4.0%) who was an abattoir worker. In the veterinarian group, all people were found negative. CONCLUSION: In our study, the variables showing important associations with the prevalence of anti-CCHFV antibodies were livestock breeding, rural areas, and age. It was concluded that our region is endemic with regard to CCHF infection and persons who had direct contact with animals are at high risk. Thus, these participants must take necessary measures to protect themselves from CCHF and should be trained by health authorities.
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We report high-performance I+ /H2 O2 catalysis for the oxidative or decarboxylative oxidative α-azidation of carbonyl compounds by using sodium azide under biphasic neutral phase-transfer conditions. To induce higher reactivity especially for the α-azidation of 1,3-dicarbonyl compounds, we designed a structurally compact isoindoline-derived quaternary ammonium iodide catalyst bearing electron-withdrawing groups. The nonproductive decomposition pathways of I+ /H2 O2 catalysis could be suppressed by the use of a catalytic amount of a radical-trapping agent. This oxidative coupling tolerates a variety of functional groups and could be readily applied to the late-stage α-azidation of structurally diverse complex molecules. Moreover, we achieved the enantioselective α-azidation of 1,3-dicarbonyl compounds as the first successful example of enantioselective intermolecular oxidative coupling with a chiral hypoiodite catalyst.
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ortho-Quinone methides are useful transient synthetic intermediates in organic synthesis. These species are most often generated in situ by the acid- or base-mediated transformation of phenols that have been pre-functionalized at a benzylic position, or by biomimetic oxidation of the corresponding ortho-alkylphenols with metal oxidants or transition-metal complexes. Here we describe a method for the transition-metal-free oxidative generation of o-QMs from ortho-alkylarenols, using hypoiodite catalysis under nearly neutral conditions, which can then be applied in one-pot tandem reactions. This method for the chemoselective oxidative generation of ortho-quinone methides may prove superior to previous methods with respect to environmental issues and scope, and can be applied to various tandem reactions such as inter- or intramolecular [4 + 2] cycloaddition, oxa-6π-electrocyclization, conjugate addition and spiroepoxidation.
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We developed a chemoselective oxidative dearomative spiroetherification and spiroamination of arenols using I+/oxone catalysis. The intramolecular dearomative C-O and C-N couplings proceeded much more efficiently under slightly acidic conditions to give the corresponding spiro adducts in higher yields compared with previous methods using transition metal or hypervalent iodine catalysts. Control experiments suggested that both hypoiodous acid and iodine might be active species for these reactions.
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OBJECTIVE: In this study, we researched the availability of Echinococcus IgG ELISA in pulmonary hydatid cysts. MATERIALS AND METHODS: Between January 2008 and December 2015, 93 successive cases, which were studied in preoperative Echinococcus IgG and histopathologically found to have pulmonary hydatid cysts, were retrospectively analyzed. Age and sex of the cases and the cyst's location, number, size, spread to other organs outside the lungs, and its condition as intact or ruptured were reviewed. RESULTS: Forty-seven (50.5%) patients were male and 46 (49.5%) patients were female; the mean age was 27.7±19.6 years. While in 56 (60.2%) cases, only lung cysts were detected, 32 (34.4%) cases presented with both lung and liver cysts. While lung cysts were single in 71 (76.3%), they were multiple in 22 (23.6%) cases (between 2 and 20 pieces). In 48 (51.6%) cases, cysts were in the right lung, and in 32 (34.4%) cases, they were in the left. In 13 (14%) cases, cysts presented in both the right and left lungs. The mean diameter of the pulmonary cysts was 6.4 cm (ranging from 2 to 19 cm). In 53 (57%) cases, hydatid cysts were ruptured, whereas in 40 (43%) cases, the cysts were intact. While general Echinococcus IgG was found to be positive in 53 (57%) cases, it was negative in 40 (43%) cases. There were 53 ruptured cases, and 48 (90.6%) of them were test-positive; however, the test was positive in only 5 (12.5%) out of the 40 cases where the cysts were intact (p<0.001). A statistically significant correlation has not been found between IgG and patient age, gender, cyst location, number of cysts, cyst diameter, and extrapulmonary involvement. CONCLUSION: Our study demonstrated that the most important factor that affects the positivity of Echinococcus IgG is the rupture of cysts. When ruptured cysts become confusing, Echinococcus IgG can contribute toward a diagnosis.
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The total synthesis of pestheic acid based on an intramolecular SNAr reaction without a nitro group and the asymmetric synthesis of (-)-maldoxin by a catalytic enantioselective oxidative dearomatization of pestheic acid are described. The reactivity of (-)-maldoxin as a diene in the Diels-Alder reaction is also investigated.
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BACKGROUND: Many serological tests have been used for the diagnosis of human brucellosis. A new serological method is identified as Brucella Coombs gel test based on the principle of centrifugation gel system similar to the gel system used in blood group determination. In this system, if Brucella antibodies were present in the serum, antigen and antibody would remain as a pink complex on the gel. Otherwise, the pink Brucella antigens would precipitate at the bottom of the gel card system. OBJECTIVE: In this study, we aimed to compare the Brucella Coombs gel test, a new, rapid screen and titration method for detection of non-agglutinating IgG with the Brucella Coombs test. MATERIALS AND METHODS: For this study, a total of 88 serum samples were obtained from 45 healthy persons and 43 individuals who had clinical signs and symptoms of brucellosis. For each specimen, Rose Bengal test, standard agglutination test, Coombs test and Brucella Coombs gel test were carried out. RESULTS: Sensitivity and specificity of Brucella Coombs gel test were found as 100.0 and 82.2%, respectively. CONCLUSION: Brucella Coombs gel test can be used as a screening test with high sensitivity. By the help of pink Brucella antigen precipitation, the tests' evaluation is simple and objective. In addition, determination of Brucella antibody by rapid titration offers another important advantage.
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Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Brucella/imunologia , Brucelose/diagnóstico , Teste de Coombs/métodos , Brucelose/sangue , Brucelose/imunologia , Brucelose/microbiologia , Estudos de Casos e Controles , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fluxo de TrabalhoRESUMO
Highly enantioselective oxidative dearomatization of 2-naphthol derivatives was achieved for the first time by using conformationally flexible organoiodine catalysts derived from 2-aminoalcohol as a chiral source. Moreover, with the use of these catalysts, excellent enantioselectivities were also achieved for 1-naphthol derivatives, which had previously been obtained with only lower enantioselectivities. Furthermore, the product obtained from the present reaction could be transformed to a highly functionalized spirolactone in high yield and with excellent stereoselectivity.
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A site-selective hydroxylative dearomatization of 2-substituted phenols to either 1,2-benzoquinols or their cyclodimers, catalyzed by 4,5-dimethyl-2-iodoxybenzenesulfonic acid with Oxone, has been developed. Natural products such as biscarvacrol and lacinileneâ C methyl ether could be synthesized efficiently under mild reaction conditions. Furthermore, both the reaction rate and site selectivity could be further improved by the introduction of a trialkylsilylmethyl substituent at the 2-position of phenols. The corresponding 1,2-quinols could be transformed into various useful structural motifs by [4+2] cycloaddition cascade reactions.