Academic literature on the topic 'Y-lactams'
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Journal articles on the topic "Y-lactams"
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Kazmierczak, Krystyna, Sibylle Lob, Gregory Stone, and Daniel F. Sahm. "1264. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa Collected < 48 Hours and ≥48 Hours Post-Admission from Pediatric Patients, ATLAS Surveillance Program 2016-2019." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S720—S721. http://dx.doi.org/10.1093/ofid/ofab466.1456.
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Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with in vitro activity against Enterobacterales (Ent) and Pseudomonas aeruginosa (Psa) carrying Class A, C and some Class D β-lactamases. We examined the in vitro activity of CAZ-AVI and comparators against presumed community-acquired (CA; cultured < 48 h after hospital admission) and hospital-acquired (HA; cultured ≥48 h post-admission) isolates collected from pediatric patients as part of the ATLAS surveillance program. Methods 6654 non-duplicate isolates were collected in 52 countries in Europe (n=3423), Latin America (n=1323), Middle East/Africa (n=1177), and Asia/Pacific (excluding China; n=731) from patients (newborn to 17 y) with lower respiratory tract (LRTI; n=1687), urinary tract (UTI; n=1631), bloodstream (BSI; n=1149), skin and soft tissue (SSTI; n=1122), and intra-abdominal (IAI; n=981) infections. Susceptibility testing was performed by CLSI broth microdilution and values were interpreted using CLSI 2021 breakpoints. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Isolates with CAZ or aztreonam MICs ≥2 µg/mL (Escherichia coli, Klebsiella spp., Proteus mirabilis) or meropenem MICs ≥2 µg/mL (all Ent species) or ≥4 µg/mL (Psa) were screened for β-lactamase genes. Results The in vitro activity of CAZ-AVI exceeded that of meropenem and other tested β-lactams against Ent (97.8% susceptible (S)) and Psa (92.1% S) collected globally from pediatric patients (Table). Percentages of susceptibility to CAZ-AVI ranged from 95.4-99.2% among CA Ent from different infection types and were reduced 0.6-1.3% among HA isolates from LRTI, UTI, SSTI, and IAI. Susceptibility to CAZ-AVI was also similar (92.6-95.8% S) among CA Psa from different infection types and was reduced 1.2-7.0% among HA isolates. Larger differences in susceptibility were typically seen for the tested comparator β-lactams. For Ent, the lowest percentages of susceptibility to the tested β-lactams were observed among isolates from BSI, while the pattern was less clear for Psa. Results Table Conclusion CAZ-AVI could provide a valuable therapeutic option for treatment of CA and HA infections caused by Ent and Psa in pediatric patients. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
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Kazmierczak, Krystyna, Greg Stone, and Daniel F. Sahm. "1568. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa Collected < 48 Hours and ≥48 Hours Post-Admission from Pediatric Patients, ATLAS Surveillance Program 2015-2018." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S783. http://dx.doi.org/10.1093/ofid/ofaa439.1748.
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Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with in vitro activity against Enterobacterales (Ent) and Pseudomonas aeruginosa (Psa) carrying Class A, C and some Class D β-lactamases. We examined the in vitro activity of CAZ-AVI and comparators against presumed community-acquired (CA; cultured < 48 h after hospital admission) and hospital-acquired (HA; cultured ≥48 h post-admission) isolates collected from pediatric patients as part of the ATLAS surveillance program. Methods 6023 non-duplicate isolates were collected in 50 countries in Europe (n=3122), Latin America (n=1220), Middle East/Africa (n=1007), and Asia/Pacific (excluding China; n=674) from patients (newborn to 17 y) with lower respiratory tract (LRTI; n=1641), urinary tract (UTI; n=1595), skin and soft tissue (SSTI; n=1027), intra-abdominal (IAI; n=949), and bloodstream (BSI; n=811) infections. Susceptibility testing was performed by CLSI broth microdilution and values were interpreted using CLSI 2020 breakpoints. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Isolates with CAZ or aztreonam MICs ≥2 µg/mL (Escherichia coli, Klebsiella spp., Proteus mirabilis) or meropenem MICs ≥2 µg/mL (all Ent species) or ≥4 µg/mL (Psa) were screened for β-lactamase genes. Results The in vitro activity of CAZ-AVI exceeded that of meropenem and other tested β-lactams against Ent (98.5% susceptible (S)) and Psa (93.1% S) collected globally from pediatric patients (Table). Percentages of susceptibility to CAZ-AVI ranged from 96.8-99.3% among CA Ent from different infection types and were reduced 0.4-1.0% among HA isolates from SSTI, IAI and BSI. Susceptibility to CAZ-AVI was also similar (92.7-95.4% S) among CA Psa from different infection types and was reduced 0.1-4.4% among HA isolates. For both Ent and Psa, the lowest percentages of susceptibility to the tested β-lactams were observed among isolates from BSI, which included a higher proportion of isolates carrying extended-spectrum β-lactamases and/or carbapenemases than isolates from other infection types. Table Conclusion CAZ-AVI could provide a valuable therapeutic option for treatment of CA and HA infections caused by Ent and Psa in pediatric patients. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
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Lei, Wen-Long, Kai-Wen Feng, Tao Wang, Li-Zhu Wu, and Qiang Liu. "Eosin Y- and Copper-Catalyzed Dark Reaction To Construct Ene-γ-Lactams." Organic Letters 20, no. 22 (November 7, 2018): 7220–24. http://dx.doi.org/10.1021/acs.orglett.8b03147.
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Tapia-Arreola, Ana K., Daniel A. Ruiz-Garcia, Hectorina Rodulfo, Ashutosh Sharma, and Marcos De Donato. "High Frequency of Antibiotic Resistance Genes (ARGs) in the Lerma River Basin, Mexico." International Journal of Environmental Research and Public Health 19, no. 21 (October 27, 2022): 13988. http://dx.doi.org/10.3390/ijerph192113988.
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The spread of beta-lactamase-producing bacteria is of great concern and the environment has been found to be a main source of contamination. Herein, it was proposed to determine the frequency of antimicrobial-resistant-Gram-negative bacteria throughout the Lerma River basin using phenotypic and molecular methods. Resistant bacteria were isolated with chromogenic media and antimicrobial susceptibility tests were used to characterize their resistance. ARGs for beta-lactams, aminoglycosides, and quinolones were detected by PCR. Species were identified by Sanger sequencing the 16S rRNA gene and the representative genomes of MDR strains were sequenced by NGS. A high variation in the number of isolates was observed in the 20 sampled sites, while observing a low diversity among the resistant bacteria. Of the 12 identified bacterial groups, C. freundii, E. coli, and S. marcescens were more predominant. A high frequency of resistance to beta-lactams, quinolones, and aminoglycosides was evidenced, where the blaCTX,qnrB, qnrS y, and aac(6′)lb-cr genes were the most prevalent. C. freundii showed the highest frequency of MDR strains. Whole genome sequencing revealed that S. marcescens and K. pneumoniae showed a high number of shared virulence and antimicrobial resistance genes, while E. coli showed the highest number of unique genes. The contamination of the Lerma River with MDR strains carrying various ARGs should raise awareness among environmental authorities to assess the risks and regulations regarding the optimal hygienic and sanitary conditions for this important river that supports economic activities in the different communities in Mexico.
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Luisa Maria Charco Roca, José María Jiménez Vizuete, and Antonio Ayelo Navarro. "Estrategias de optimización de uso de betalactámicos." Revista Electrónica AnestesiaR 11, no. 9 (October 2, 2019): 3. http://dx.doi.org/10.30445/rear.v11i9.786.
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Se han propuesto varias estrategias de mejora con la finalidad de optimizar el uso de antibióticos en los pacientes críticos. Entre ellas destacan la de-escalada, el ciclado, el tratamiento anticipado o el uso de parámetros farmacocinéticos/farmacodinámicos para ajustar la dosificación. Las alteraciones fisiopatológicas que ocurren en el paciente crítico condicionan la farmacocinética y la farmacodinamia de los antibióticos, especialmente de los betalactámicos. Por ello, la predicción del resultado antimicrobiano basado en sus concentraciones plasmáticas, puede ser muy difícil de establecer en el lugar de acción, debido a dichas alteraciones, pudiendo tener esto consecuencias clínicamente relevantes. Se puede mejorar el perfil farmacodinámico de los betalactámicos, mediante una exposición más prolongada con dosis más frecuentes o con infusiones continuas o extendidas, especialmente para tratar bacterias multirresistentes. ABSTRACT OPTIMIZATION STRATEGIES FOR THE USE OF BETA -LACTAMS. The importance of the pathophysiological peculiarities in the critically ill patient. There are several strategies aimed at improving the use of antibiotics in critical patients. These strategies include de-escalation, cycling, early treatment or the use of pharmacokinetic / pharmacodynamic parameters to adjust the dosage. The pathophysiological changes that occur in the critical patient can condition the pharmacokinetics and pharmacodynamics paramethers of antibiotics, especially in beta-lactams. Therefore, anticipating the antimicrobial result based on their plasma concentrations in the place of action can be very difficult to establish, which, in turn, may have clinically relevant consequences. The pharmacodynamic profile of beta-lactams can be improved, through longer exposure with more frequent doses or with continuous or extended infusions, especially to treat multiresistant bacteria.
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Bjergum, Matthew W., Erin F. Barreto, Marc H. Scheetz, Andrew D. Rule, and Paul J. Jannetto. "Stability and Validation of a High-Throughput LC-MS/MS Method for the Quantification of Cefepime, Meropenem, and Piperacillin and Tazobactam in Serum." Journal of Applied Laboratory Medicine 6, no. 5 (June 4, 2021): 1202–12. http://dx.doi.org/10.1093/jalm/jfab036.
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Abstract Background The class of antibiotics known as β-lactams are a commonly used due to their effectiveness and safety. Therapeutic drug monitoring has been proposed but requires an accurate assay along with well-characterized preanalytic stability, as β-lactams are known to be relatively unstable. Methods A high-throughput LC-MS/MS assay validation and stability study was performed for cefepime, meropenem, and piperacillin and tazobactam in serum. Patient samples, standards, and QCs were crashed with acetonitrile containing internal standard. Following centrifugation, an aliquot of the supernatant was diluted with clinical laboratory reagent water and analyzed by LC-MS/MS. Results The assay showed linearity between 0.5 and 60 µg/mL for each analyte. The intra- and interassay reproducibility at 3 different concentrations (approximately 2, 25, and 40 µg/mL) was <5% for each analyte. Accuracy studies for each analyte were compared using linear regression and demonstrated: slope = 1.0 ± 0.1; r2 ≥ 0.980; and y intercept 95% CI that included zero. Minimal ion suppression or enhancement was observed, and no significant carryover was observed up to 500 µg/mL of each analyte. Stability studies demonstrated significant loss in serum for each analyte at ambient and refrigerated temperatures (2–8 °C) and at −20 °C over days or weeks. In contrast, when stored at −80 °C, no significant loss was observed. Conclusions The LC-MS/MS assay showed acceptable performance characteristics for quantitation of β-lactams. With well-characterized stability, this assay can be used with residual specimens for pharmacokinetic modeling, which may lead to individualized dosing and improved patient care.
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Skagseth, Susann, Trine Josefine Carlsen, Gro Elin Kjæreng Bjerga, James Spencer, Ørjan Samuelsen, and Hanna-Kirsti S. Leiros. "Role of Residues W228 and Y233 in the Structure and Activity of Metallo-β-Lactamase GIM-1." Antimicrobial Agents and Chemotherapy 60, no. 2 (December 7, 2015): 990–1002. http://dx.doi.org/10.1128/aac.02017-15.
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ABSTRACTMetallo-β-lactamases (MBLs) hydrolyze virtually all β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. The worldwide emergence of antibiotic-resistant bacteria harboring MBLs poses an increasing clinical threat. The MBL German imipenemase-1 (GIM-1) possesses an active site that is narrower and more hydrophobic than the active sites of other MBLs. The GIM-1 active-site groove is shaped by the presence of the aromatic side chains of tryptophan at residue 228 and tyrosine at residue 233, positions where other MBLs harbor hydrophilic residues. To investigate the importance of these two residues, eight site-directed mutants of GIM-1, W228R/A/Y/S and Y233N/A/I/S, were generated and characterized using enzyme kinetics, thermostability assays, and determination of the MICs of representative β-lactams. The structures of selected mutants were obtained by X-ray crystallography, and their interactions with β-lactam substrates were modeledin silico. Steady-state kinetics revealed that both positions are important to GIM-1 activity but that the effects of individual mutations vary depending on the β-lactam substrate. Activity against type 1 substrates bearing electron-donating C-3/C-4 substituents (cefoxitin, meropenem) could be enhanced by mutations at position 228, whereas hydrolysis of type 2 substrates (benzylpenicillin, ampicillin, ceftazidime, imipenem) with methyl or positively charged substituents was favored by mutations at position 233. The crystal structures showed that mutations at position 228 or the Y233A variant alters the conformation of GIM-1 loop L1 rather than that of loop L3, on which the mutations are located. Taken together, these data show that point mutations at both positions 228 and 233 can influence the catalytic properties and the structure of GIM-1.
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Fernández Balaguer, Gonzalo, Carmen del Águila, Carolina Hurtado Marcos, and Rubén Agudo Torres. "ANCESTRAL RECONSTRUCTION OF A β-LACTAMASE AND COMPARISON WITH ITS EXTANT PROTEINS." Anales de la Real Academia Nacional de Farmacia, no. 87(02) (2021): 155–70. http://dx.doi.org/10.53519/analesranf.2021.87.02.05.
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The β-lactamases are proteins of bacterial origin that are characterized by hydrolyzing antibiotics β-lactams, conferring microbial resistance against them. They are a heterogeneous family of proteins very relevant from a health point of view due to the ease they present to acquire resistance to new drugs due to their high capacity for evolution. The in vitro evolution of these proteins has served not only to develop their characterization and improve their knowledge, but as a new line of research that allows to predictively identify residues involved in the acquisition of antibiotic resistance. At the same time, the method of ancestral protein reconstruction has been revealed as a novel and useful tool to understand the evolution of β-lactamases and understand some of their characteristics such as their promiscuity. In this work, a study of ancestral β-lactamases reconstructed from the phylogeny of existing class A β-lactamases has been carried out. Of the four ancestral proteins studied, one has been obtained that is functional and has compared its hydrolytic activity with that of four of its current counterparts against eight β-lactam drugs. This ancestral protein has been shown to have a more generalistic antibiotic activity than any of the current proteins studied. In addition, the active ancestral protein showed more resistance to one of the drugs used than the rest of β-lactamases existing. Finally these results have been discussed and from them it is argued why reconstructed ancestral sequences can be a very attractive starting point when it comes to direct evolution of proteins for obtaining proteins of biotechnological interest.
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Ito, H., Y. Arakawa, S. Ohsuka, R. Wacharotayankun, N. Kato, and M. Ohta. "Plasmid-mediated dissemination of the metallo-beta-lactamase gene blaIMP among clinically isolated strains of Serratia marcescens." Antimicrobial Agents and Chemotherapy 39, no. 4 (April 1995): 824–29. http://dx.doi.org/10.1128/aac.39.4.824.
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The distribution of strains producing metallo-beta-lactamase among 105 strains of Serratia marcescens was investigated. All of these strains were isolated in seven general hospitals located in Aichi Prefecture, Japan, from April to May 1993. Southern hybridization analysis suggested that four S. marcescens strains, AK9373, AK9374, AK9385, and AK9391, had a metallo-beta-lactamase genes similar to the blaIMP gene found by our laboratory (E. Osano, Y. Arakawa, R. Wacharotayankun, M. Ohta, T. Horii, H. Ito, F. Yoshimura, and N. Kato, Antimicrob. Agents Chemother. 38:71-78, 1994), and these four strains showed resistance to carbapenems as well as to the other broad-spectrum beta-lactams. In particular, strains AK9373, AK9374, and AK9391 showed an extraordinarily high-level resistance to imipenem (MICs, > or = 64 micrograms/ml), whereas strain AK9385 demonstrated moderate imipenem resistance (MIC, 8 micrograms/ml). The imipenem resistance of AK9373 was transferred to Escherichia coli CSH2 by conjugation with a frequency of 10(-5). The DNA probe of the blaIMP gene hybridized to a large plasmid (approximately 120 kb) transferred into the E. coli transconjugant as well as to the large plasmids harbored by AK9373. On the other hand, although we failed in the conjugational transfer of imipenem resistance from strains AK9374, AK9385, and AK9391 to E. coli CSH2, imipenem resistance was transferred from these strains to E. coli HB101 by transformation. A plasmid (approximately 25 kb) was observed in each transformant which acquired imipenem resistance. The amino acid sequence at the N terminus of the enzyme purified from strain AK9373 was identical to that of the metallo-beta-lactamase IMP-1. In contrast, strains ES9348, AK9386, and AK93101, which were moderately resistant to imipenem (MICs, > or = 4 to < or = 8 micrograms/ml), had no detectable blaIMP gene. As a conclusion, 19% of clinically isolated S. marcescens strains in Aichi Prefecture, Japan, in 1993 were resistant to imipenem (MICs, > or = 2 micrograms/ml), and strains which showed high-level imipenem resistance because of acquisition of a plasmid-mediated blaIMP-like metallo-beta-lactamase gene had already proliferated as nosocomial infections, at least in a general hospital.
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Sebbane, Florent, and Nadine Lemaître. "Antibiotic Therapy of Plague: A Review." Biomolecules 11, no. 5 (May 12, 2021): 724. http://dx.doi.org/10.3390/biom11050724.
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Plague—a deadly disease caused by the bacterium Yersinia pestis—is still an international public health concern. There are three main clinical forms: bubonic plague, septicemic plague, and pulmonary plague. In all three forms, the symptoms appear suddenly and progress very rapidly. Early antibiotic therapy is essential for countering the disease. Several classes of antibiotics (e.g., tetracyclines, fluoroquinolones, aminoglycosides, sulfonamides, chloramphenicol, rifamycin, and β-lactams) are active in vitro against the majority of Y. pestis strains and have demonstrated efficacy in various animal models. However, some discrepancies have been reported. Hence, health authorities have approved and recommended several drugs for prophylactic or curative use. Only monotherapy is currently recommended; combination therapy has not shown any benefits in preclinical studies or case reports. Concerns about the emergence of multidrug-resistant strains of Y. pestis have led to the development of new classes of antibiotics and other therapeutics (e.g., LpxC inhibitors, cationic peptides, antivirulence drugs, predatory bacteria, phages, immunotherapy, host-directed therapy, and nutritional immunity). It is difficult to know which of the currently available treatments or therapeutics in development will be most effective for a given form of plague. This is due to the lack of standardization in preclinical studies, conflicting data from case reports, and the small number of clinical trials performed to date.
Dissertations / Theses on the topic "Y-lactams"
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McGonagle, Fiona I. "The development of one-pot tandem reactions for the synthesis of polycyclic y-lactams." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3684/.
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A novel tandem process has been developed for the stereoselective synthesis of bicyclic γ-lactams. Treatment of an allylic alcohol with trichloroacetonitrile, in the presence of DBU, affords the corresponding allylic trichloroacetimidate. This is then subjected to a tandem Overman rearrangement/RCM/Kharasch cyclisation, forming the desired bicyclic lactam in high yield and high enantiomeric excess. Overall, the one-pot tandem process involves three mechanistically distinct processes catalysed by palladium(II) (step 1) and Grubbs 1st generation catalyst (steps 2 and 3). The use of a thermal Overman rearrangement in tandem with the Grubbs catalysed RCM/Kharasch cyclisation was also investigated. Furthermore, a microwave-assisted tandem process was developed which resulted in the accelerated synthesis of the desired bicyclic γ-lactams. A two-step tandem process was then developed for the synthesis of bicyclic allylic amides, a closely related core unit to that found in a number of important commercially available drugs. Finally, progress has been made towards the total synthesis of (±)-deethylibophyllidine, which will utilise a tandem RCM/Kharasch cyclisation to construct the C and D rings of the natural product.
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André, Marcelo Fabiano 1978. "Sintese de B-piperonil-y-butirolactona e B-lactamas utilizando reações de Morita-Baylis-Hillman." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/250241.
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Orientador: Fernando Antonio Santos CoelhoDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica
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Resumo: As b-piperonil-g-butirolactonas são intermediários importantes, tendo em vista que a partir delas é possível dar origem a uma série de lignanas, classe de substâncias de grande interesse científico, por apresentarem diversas atividades biológicas, tais como: antiretroviral, antitumoral, antimalárica, entre outras. Neste trabalho realizamos estudos visando melhorar a diastereosseletividade na preparação de g-butirolactonas com estereoquímica relativa trans, já que a cis já era preparada com boa diastereosseletividade em nosso laboratório. A metodologia desenvolvida baseia-se na redução de um b-ceto-éster obtido a partir da oxidação de um a-ciano-metil-b-hidroxi-éster, este último obtido com um bom rendimento a partir de uma reação de adição de Michael sobre um aduto de Morita-Baylis-Hillman ( MBH). Na segunda parte do trabalho preparamos b-amino-ésteres a partir dos adutos de Morita-Baylis- Hillman (MBH). Utilizamos como estratégia uma reação de adição do tipo Michael com várias aminas. Os b-amino-ésteres foram obtidos com rendimentos variando de 78-93%. Os produtos foram caracterizados e a estereoquímica relativa foi determinada, por nOe, através da formação de um intermediário oxazinanona. Esses b-amino-ésteres são importantes intermediários para a síntese de heterociclos, tais como b-lactamas e oxazinanonas funcionalizadas.
Abstract: The b-piperonil-g-butirolactones are important synthetic intermediates, since they can be used as substrates for the synthesis of different type of lignans, a class of substances of great scientific interest. Lignans exhibit relevant biological activites, as anti-tumoral, anti-retroviral, anti-malarial, etc. In this work, studies have been carried out aiming at improving the diastereoselectivity for the preaparation of butirolactones having anti relative stereochemistry. A method to synthesize g-butirolactone have already been established in our laboratory. The methodology used was based on the the stereoselective reduction of a b-ketoester prepared from the oxidation of a a-cyanomethyl-b-hydroxy-ester. The latter was promptly prepared, in good yields, from a cyanide 1,4 addition over the double bond of Morita-Baylis-Hillman (MBH) adducts. In the second part of this work, we have prepared several b-amino-esters from Morita-Baylis- Hillman (MBH) adducts. The strategy was based also on a Michael addition of different amines over the double bond of MBH adducts. The b-amino-esters were obtained in good yield. Their stereochemistries were determined by nOe experiments of the corresponding oxazinanones. These b-amino-esters are important intermediates for the synthesis of heterocycles, as b-lactams and functionalized oxazinanones.
Mestrado
Quimica Organica
Mestre em Química
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Le, Goff Ronan. "Utilisation de réactions tandem et domino pour l'accès rapide à des hétérocycles azotés." Thesis, Le Havre, 2015. http://www.theses.fr/2015LEHA0014/document.
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La présence importante des hétérocycles azotés en chimie organique et médicinale explique le grand intérêt et les très nombreuses recherches dont ils font l’objet. Parmi tous ces motifs, les pyrrolidines ainsi que les γ- et δ-lactames bicycliques ont tout particulièrement focalisé notre attention. En se basant sur des résultats antérieurs obtenus au laboratoire nous avons mis au point deux nouvelles voies d’accès rapides et innovantes pour accéder diastéréosélectivement à ces motifs. D’une part une réaction tandem aza-MIRC (Michael Induced Ring Closure) a permis de former des pyrrolidines polysubstituées et d’autre part une séquence domino oxa-Michael/aza-MIRC a donné accès à de très nombreux γ- et δ-lactames bicycliques. Ces deux méthodes ont, en outre, été appliquées à la synthèse de composés d’intérêts connus pour leurs activités biologiques. La séquence aza-MIRC a été utilisée pour les synthèses totale et formelle respectivement des alcaloïdes Coerulescine et Martinelline, tandis que le processus oxa-Michael/aza-MIRC a été employé pour accéder de manière stéréosélective à des composés spirooxindoliques énantioenrichis. En parallèle du développement de ces deux méthodes, une étude mécanistique poussée de la séquence oxa-Michael/aza-MIRC a été réalisée au moyen de calculs théoriques. Cette étude a permis d’expliquer la majeure partie des résultats obtenus en fournissant un outil puissant capable d’anticiper, dans une certaine mesure, la réactivité de la séquence domino oxa-Michael/aza-MIRCN-heterocycle scaffolds are found in many synthetic and medicinal chemical compounds explaining the high interest for developing efficient synthetic methodologies to reach such structures. In that field, our group has developed over the years innovative routes to y-lactams and bicyclic γ- and δ-lactams using tandem and domino reactions. Based on those previous works, we have developed two new methods to synthesize N-heterocycles. A tandem aza-MIRC (Michael Induced Ring Closure) sequence have been investigated to access pyrrolidines whereas the bicyclique scaffold of bislactames have been obtained using a domino oxa-Michael/aza-MIRC pathway. These two new methods have been then applied to the syntheses of more complexes and thus challenging backbones. The aza-MIRC tandem process have been used for the total and formal synthesis of alkaloids Coerulescine and Martinelline, respectively, whereas the domino oxa-Michael/aza-MIRC sequence has proved to be a powerful tool for stereoselective access to enantioenriched spirooxindolic compounds. DFT calculations studies have allowed elucidation of the diastereoselectivity and double chirality transfer of the domino reaction therefore could be used in the future to develop efficient total syntheses
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Bisol, Tula Beck. "Preparação e estudo da reatividade de oxirano e aziridino acetatos visando a síntese de y-lactamas funcionalizadas." reponame:Repositório Institucional da UFSC, 2012. http://repositorio.ufsc.br/xmlui/handle/123456789/95900.
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Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas, Programa de Pós-graduação em Química, Florianópolis, 2011Made available in DSpace on 2012-10-26T06:58:03Z (GMT). No. of bitstreams: 1 290257.pdf: 3957996 bytes, checksum: 414ed38650f5e07f28471b7990743d84 (MD5)
Desenvolveu-se um método simples e eficiente para a síntese diastereodivergente de .- lactamas ß,.-difuncionalizadas com configuração anti ou sin a partir de oxirano e aziridino acetatos. A etapa inicial envolveu a preparação de anti .-azido-ß-hidróxi ésteres pela azidólise de alquil e aril oxirano acetatos. Utilizando uma abordagem diastereodivergente, sin .-azido-ß-hidróxi ésteres foram obtidos pela bromólise dos oxirano acetatos seguida de substituição com azoteto. As condições reacionais foram otimizadas e os produtos de abertura foram obtidos com excelentes regio- e diastereosseletividades. A ciclização redutiva dos anti e sin .-azido-ß-hidróxi ésteres via hidrogenação catalítica sob condições brandas, levou às ß-hidróxi .-lactamas em ótimos rendimentos. Também se estudou o efeito de grupos volumosos ligados ao carbono C-ß sobre as reações de ciclização redutiva. Da mesma forma, a azidólise regio- e diastereosseletiva de anti e sin aziridino acetatos (preparados a partir dos .-azido-ß-hidróxi ésteres) seguida de ciclização redutiva dos anti e sin ß-amino-.-azido ésteres levou às ß-amino .-lactamas em ótimos rendimentos. Ampliou-se o método para a síntese assimétrica da (4R,5S)-5-fenil-4-hidroxipirrolidin-2-ona a partir do respectivo oxirano acetato quiral. As principais características deste método são o uso de reagentes simples, condições brandas e alta eficiência química.
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Matute, Morales Ricardo. "Estudio teórico de la estructura electrónica y de los mecanismos de tautomería lactama-lactima en bilinas de fitocromo." Tesis, Universidad de Chile, 2010. http://www.repositorio.uchile.cl/handle/2250/105186.
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Jung, Young Chun. "A new approach to kainoids : total syntheses of (-)-kainic acid and (+)-allokainic acid." [Tampa, Fla] : University of South Florida, 2006. http://purl.fcla.edu/usf/dc/et/SFE0001464.
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