Novel Aspects on the Preparation of Spirocyclic and Fused Unusual β-Lactams

Capítulo 1, pp 1-48β-Lactam antibiotics have occupied a central role in the fight against pathogenic bacteria and the subsequent rise in quality of life for the world population as a whole. However, the extensive use of common β-lactam antibiotics such as penicillins and cephalosporins in medicine has resulted in an increasing number of resistant strains of bacteria through mutation and β-lactamase gene transfer. The resistance of bacteria to the classical β-lactam antibiotics can be overcome, e.g., by using novel β-lactam moieties in drugs which show much higher stability towards these resistance bacteria. In addition, there are many important nonantibiotic uses of 2-azetidinones in fields ranging from enzyme inhibition to gene activation. These biological activities, combined with the use of these products as starting materials to prepare α- and β-amino acids, alkaloids, heterocycles, taxoids, and other types of compounds of biological and medicinal interest, provide the motivation to explore new methodologies for the synthesis of substances based on the β-lactam core. The aim of this chapter is to provide a survey of the types of reactions used to prepare non-conventional spirocyclic and fused β-lactams, concentrating on the advances that have been made in the last decade, and in particular in the last five years. We will draw special attention to radical cyclizations, cycloaddition reactions, and transition metal-catalyzed reactions.Peer reviewe

Novel achievements with an old metal: Copper-promoted synthesis of four-membered azacycles

The synthesis of four-membered azacycles is of importance because of the chemical and biological relevance of these compounds. Recent progress in copper-catalyzed reactions has been applicable to a variety of research fields, such as heterocyclic synthesis. The aim of the current review is to summarize the synthesis of strained four-membered ring taking advantage of copper catalyzed and mediated processes. © 2014 The Royal Society of Chemistry.Peer Reviewe

Gold-catalyzed direct cycloketalization of acetonide-tethered alkynes in the presence of water

A methodology for the direct preparation of bridged acetals from acetonide-tethered alkynes under gold catalysis in the presence of water has been developed. The bicyclic ring structures bearing a bridged five-membered ring arise from the regioselective bis-oxycyclization by initial attack of the oxygen atom to the internal alkyne carbon. © 2012 Elsevier Ltd. All rights reserved.Peer Reviewe

Diseño de un dispositivo para la estimación del nivel de estrés basado en coherencia fisiológica

[ES] El estrés se ha convertido en una de las mayores afecciones en la sociedad actual pudiendo llegar a dañar la salud mental de los individuos o ocasionando daños físicos en distintos aparatos y sistemas del organismo a largo plazo. Para intentar establecer una estimación del nivel de estrés se obtienen tres señales fisiológicas, ECG, PPG y respiración mediante sensores analógicos y una placa microcontroladora. A partir de ellas se obtienen otras señales indirectas como la variabilidad cardíaca y el tiempo de transito de pulso que, mediante cálculos en el dominio frecuencial y temporal, el dispositivo obtiene un índice de coherencia global que nos permite aproximar de forma empírica dicho nivel de estrés.[EN] Stress has become one of the biggest issues nowadays. It can damage mental health of individuals or cause physical damage to different systems of the body in long term. To try to establish an estimate of the stress level, three physiological signals, ECG, PPG and breathing are obtained by means of analog sensors and a microcontroller. From them, other indirect signals such as cardiac variability and pulse transit time are obtained, which, through calculations in the frequency and temporal domain, the device obtains a global coherence index that allows us to empirically approximate said stress levelTornero Almendros, P. (2021). Diseño de un dispositivo para la estimación del nivel de estrés basado en coherencia fisiológica. Universitat Politècnica de València. http://hdl.handle.net/10251/173760TFG

Stereoselective cyanation of 4-formyl and 4-imino-β-lactams: Application to the synthesis of polyfunctionalized γ-lactams

The stereoselective reaction of 4-oxoazetidine-2-carbaldehydes and their corresponding imines with cyanide-based reagents give β-lactam α-aminonitriles, which are chameleonic building blocks for the controlled synthesis of a variety of new compounds including functionalized γ-lactams, succinimide derivatives, and diamino-lactams derivatives in optically pure form. © 2012 Elsevier Ltd. All rights reserved.Peer Reviewe

Вопросы воспитания в советской школе

Gold-catalyzed hydroarylation reaction of β-lactam-tethered allenyl indoles gives azeto-oxepino­[4,5-<i>b</i>]­indol-2-ones, tetrahydroazeto-azocino­[3,4-<i>b</i>]­indol-2-ones, and hexahydroazeto-azepino­[3,4-<i>b</i>]­indol-2-ones with very high levels of stereo- and regioselectivity, the 7-<i>exo</i> and 8-<i>endo</i> carbocyclization modes by attack of the indole group toward either the internal or the terminal allene carbon, respectively, being favored. Hydroarylation across the central carbon of the allene moiety has not been detected. The controlled gold-catalyzed annulations allowed the formation of fused β-lactams without harming the sensitive four-membered heterocycle. Besides, a novel gold-catalyzed domino process, namely, the allenic hydroarylation/N1–C4 β-lactam bond breakage to afford dihydro-oxepino­[4,5-<i>b</i>]­indole-4-carboxamides, has been discovered

Iodine recycling via 1,3-migration in iodoindoles under metal catalysis

3-Substituted (indol-2-yl)-α-allenols show divergent patterns of reactivity under metal catalysis. An unprecedented intramolecular 1,3-iodine migration is described. © 2013 The Royal Society of Chemistry.Peer Reviewe

Solvent-Controlled Switching of Cycloisomerization to Transposition in the Ag/Cu-Promoted Reaction of Terminal α-Allenols

We report herein a study on the Ag/Cu-catalyzed reactivity of α-allenols. The focus was the development of new methodologies for cyclization and/or transposition of this moiety. By simple solvent switch, the divergent preparation of dihydrofurans and 3-halo-3-alkenals in a controlled manner has been reached

Antimicrobial, Anticancer and Multidrug-Resistant Reversing Activity of Novel Oxygen-, Sulfur- and Selenoflavones and Bioisosteric Analogues

Multidrug resistance of cancer cells to cytotoxic drugs still remains a major obstacle to the success of chemotherapy in cancer treatment. The development of new drug candidates which may serve as P-glycoprotein (P-gp) efflux pump inhibitors is a promising strategy. Selenium analogues of natural products, such as flavonoids, offer an interesting motif from the perspective of drug design. Herein, we report the biological evaluation of novel hybrid compounds, bearing both the flavone core (compounds 1–3) or a bioisosteric analogue core (compounds 4–6) and the triflyl functional group against Gram-positive and Gram-negative bacteria, yeasts, nematodes, and human colonic adenocarcinoma cells. Results show that these flavones and analogues of flavones inhibited the activity of multidrug resistance (MDR) efflux pump ABCB1 (P-glycoprotein, P-gp). Moreover, the results of the rhodamine 123 accumulation assay demonstrated a dose-dependent inhibition of the abovementioned efflux pump. Three compounds (4, 5, and 6) exhibited potent inhibitory activity, much stronger than the positive control, verapamil. Thus, these chalcogen bioisosteric analogues of flavones become an interesting class of compounds which could be considered as P-gp efflux pump inhibitors in the therapy of MDR cancer. Moreover, all the compounds served as promising adjuvants in the cancer treatment, since they exhibited the P-gp efflux pump modulating activity