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Catalyst-free hydroamination and hydrothiolation of alkenes have been achieved in an aqueous medium. The anti-Markovnikov addition works efficiently in suspended water at room temperature and allows straightforward access to centhaquine, a drug used for the management of hypovolemic shocks in critically ill patients, and its derivatives. Various primary and secondary amines, thiols, and hydrazides were successfully reacted with a number of heteroaryl/aryl-alkenes. The scalability of the process has been demonstrated by synthesizing centhaquine at a 19.65 g scale. A comparative analysis of the present process with previous approaches has been provided on the basis of green chemistry metrics.
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Pseudomonas aeruginosa (P. aeruginosa) infection is becoming a severe health hazard and needs early diagnosis with high specificity. However, the non-specific binding of a biosensor is a challenge to the current bacterial detection system. For the first time, we chemically synthesized a galactose tripod (GT) as a P. aeruginosa-specific ligand. We conjugated GT to a photothermally active fluorescent nanocomposite (Au@SiO2-TCPP). P. aeruginosa can be detected using Au@SiO2-TCPP-GT, and additionally ablated as well using synergistic photothermal and photodynamic therapy. Molecular dynamics and simulation studies suggested better binding of GT (binding energy = -6.6 kcal mol-1) with P. aeruginosa lectin than that of galactose monopod (GM) (binding energy = -5.9 kcal mol-1). Furthermore, a binding study was extended to target P. aeruginosa, which has a galactose-binding carbohydrate recognition domain receptor. The colorimetric assay confirmed a limit of detection (LOD) of 104 CFU mL-1. We also looked into the photosensitizing property of Au@SiO2-TCPP-GT, which is stimulated by laser light (630 nm) and causes photoablation of bacteria by the formation of singlet oxygen in the surrounding media. The cytocompatibility of Au@SiO2-TCPP-GT was confirmed using cytotoxicity assays on mammalian cell lines. Moreover, Au@SiO2-TCPP-GT also showed non-hemolytic activity. Considering the toxicity analysis and efficacy of the synthesized glycan nanocomposites, these can be utilized for the treatment of P. aeruginosa-infected wounds. Furthermore, the current glycan nanocomposites can be used for bacterial detection and ablation of P. aeruginosa in contaminated food and water samples as well.
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Stereoselective difunctionalizations of the terminal and internal alkynes with various sulfinates and isocyanides have been achieved to prepare (Z)-/(E)-ß-sulfonylacrylamides. The (Z)-ß-sulfonylacrylamides were generated via a one-pot process that involves the reaction of terminal alkynes with sulfinates and isocyanides in the presence of iodine in sequential manner. The (E)-ß-sulfonylacrylamides were prepared in a two-step synthesis via palladium(II)-catalyzed addition of isocyanide to (E)-ß-iodovinylsulfones synthesized from alkynes.
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Alquinos , Yodo , Paladio , Cianuros , CatálisisRESUMEN
Nanoglycoclusters, an upcoming class of functional nanomaterial are known to drive various processes like detection, imaging, targeting proteins, cells, and bacteria. Nanoglycoclusters are a type of nanomaterial functionalized with various glycans. The array of glycan in multiple copies enhances binding affinity with proteins. Selective and sensitive bacteria/lectin interactions using nanomaterials are an emerging area of research. The measurement of different ligand receptor interactions require sophisticated analytical tools that limit the application in biosensor domain. Recently, colorimetric biosensors gained importance in the field of the biosensor for the detection of bacteria/lectins. Herein we have demonstrated that different size of gold nanoparticles (AuNPs) along with various polyethylene glycol (PEG) linkers, functionalized with synthesized monopod and tripod of mannose and galactose that have different bacteria/lectins specificity. The newly synthesized nanoglycoclusters were able to discriminate between different lectins and bacteria. The aggregation of specific nanoglycocluster upon interaction with specific bacteria/lectins revealed that mannose monopod (MM) and mannose tripod (MT) are specific to Escherichia coli and concanavalin A (ConA) lectin, while galactose monopod (GM) and galactose tripod (GT) are specific to Pseudomonas aeruginosa and Peanut agglutinin (PNA) lectin. Further, the binding events depict the affinity of tripod glycans is more with respect to its corresponding monopod glycans. Our findings explored the potential of colorimetric sensing depending upon the size of AuNPs, linker length, specificity, along with glycans density to develop user friendly diagnostic system for the detection of bacteria.
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Técnicas Biosensibles , Nanopartículas del Metal , Bacterias , Colorimetría , Oro , PolisacáridosRESUMEN
A novel method for the generation of uniquely functionalized piperazinones by utilizing post-Ugi functionalization is described. The method involves an Ugi reaction with aminoacetaldehyde dimethyl acetal, followed by acid-mediated cyclization to generate the iminium precursor that was subjected to nucleophilic addition in a diastereoselective manner. The method was also employed to synthesize trans-dragmacidine C and praziquantel-like molecules.
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Macrocyclic alkaloids (macrolides) and cyclopeptides have an immense range of applications in drug discovery research because of their natural abundance and potential biological and physicochemical properties. Presently, more than 100 approved drugs or clinical drug candidates contain macrocyclic scaffolds as the biologically active component. This review provides an interesting perspective about the use of amino acid-derived chiral pools versus other methods derived from miscellaneous synthons towards the total synthesis of non-peptidic macrolides. The synthetic routes and the key strategies involved in the total syntheses of ten natural macrolides have been discussed. Both the amino acid-derived and non-amino acid-derived synthetic routes have been illustrated to present a comparative study between the two approaches.
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Alcaloides/química , Aminoácidos/química , Macrólidos/síntesis química , Péptidos Cíclicos/química , Descubrimiento de Drogas , Macrólidos/químicaRESUMEN
The present study describes a robust and general method for the synthesis of C(1)-carboxamides through IBX-mediated oxidative addition of isocyanides to tryptolines and 1,2,3,4-tetrahydroisoquinolines. In this transformation, IBX plays a dual role of an oxidant and Lewis acid to activate imine facilitating isocyanide addition. Detailed mechanistic investigations were performed by isotopic labeling and real-time NMR experiments. The method was utilized for the gram scale syntheses of two alkaloids alangiobussine and alangiobussinine in 63% and 45% overall yield, respectively.