The integration of multicomponent reactions (MCRs), which offer a rapid and efficient approach to synthesize complex molecular scaffolds, with continuous flow platforms is an increasingly recognized strategy in green synthesis. This association enables precise control over reaction parameters, including improved kinetics and selectivity, reduced reaction times, enhanced yields and scalabilities, while aligning with sustainable and green chemistry principles through resource utilization, minimized waste, and reduced environmental impact. This review presents a critical analysis of recent studies covering the MCR-continuous flow association, with a focus on achieving greener and more sustainable synthesis practices.
View Article and Find Full Text PDFHerein, we present an overview of continuous flow chemistry, including photoflow and electroflow technologies in the preparation of active pharmaceutical ingredients (APIs) and fine chemical intermediates. Examples highlighting the benefits and challenges associated with continuous flow processes, mainly involving continuous thermal, photo- and electrochemical transformations, are drawn from the relevant literature, especially our experience and collaborations in this area, with emphasis on the synthesis and prospective scale-up.
View Article and Find Full Text PDFChronic diseases such as cystic fibrosis, inflammatory bowel diseases, rheumatoid arthritis, and cardiovascular illness have been linked to a decrease in selenium levels and an increase in oxidative stress. Selenium is an essential trace element that exhibits antioxidant properties, with selenocysteine enzymes like glutathione peroxidase being particularly effective at reducing peroxides. In this study, a series of synthetic organoselenium compounds were synthesized and evaluated for their potential antioxidant activities.
View Article and Find Full Text PDFA transition-metal free methodology for the chemoselective reduction of benzylidene thiazolidine-2,4-diones and similar heterocycles is described, allowing the preparation of a broad scope of the corresponding reduced derivatives in up to 90% yield. The protocol has a simple and safe experimental setup, in which water was employed as the hydrogen source. To further demonstrate the synthetic utility of this transformation, the antidiabetic API Pioglitazone was prepared in 81% yield.
View Article and Find Full Text PDFMulticomponent reactions (MCRs) are processes in which three or more starting materials are combined in the same reaction vessel, forming an adduct that contains all or most of the atoms of the starting materials. MCRs are one-pot processes that provide attractive advantages for the total synthesis of target molecules. These reactions allow rapid access to structurally complex adducts from particularly simple starting materials.
View Article and Find Full Text PDFOver the last two decades, with the advent of continuous flow technologies, continuous processes have emerged as a major area in organic synthesis. In this context, continuous flow processes have been increasing in the preparation of Active Pharmaceutical Ingredients (APIs) and fine chemicals, such as complex synthetic intermediates, agrochemicals, and fragrances. Thus, the development of multi-step protocols has attracted special interest from the academic and industrial chemistry communities.
View Article and Find Full Text PDFA synthetic protocol for the preparation of α-acyl aminocarboxamides and α-amino amidines is proposed. The selectivity toward each of these two possible products was tuned by simple modifications of the reaction conditions. A broad scope is presented, allowing access to the desired products in up to 87% (Ugi adduct) and 93% (α-amino amidine).
View Article and Find Full Text PDFA transition metal-free protocol for the preparation of fluorescent and non-fluoresent 3-methylthio-4-arylmaleimides in a single step through a new rearrangement from thiazolidine-2,4-diones is described. By employing the optimized reaction conditions, a broad scope of derivatives was prepared in ≤97% yield. The reaction tolerated several substituted aryl groups, including the challenging preparation of pyridyl-containing derivatives.
View Article and Find Full Text PDFTheoretical calculations, associated with control experiments, were carried out to gain insights into the mechanism and origin of enantioselectivity in the phosphoric-acid-catalyzed dynamic kinetic resolution of azlactones. The results revealed a Münchnone intermediate as the key species involved in the isomerization of azlactone rings. The developed model was successfully employed in the comprehension and prediction of enantioselectivity under diverse of reaction conditions, including alcoholysis and aminolysis protocols.
View Article and Find Full Text PDFA novel electron-donor-acceptor (EDA) complex-enabled flow photochemical hydrotrifluoromethylation of unsaturated β-keto esters is described. The developed protocol has an easy experimental procedure and does not require the use of transition-metal-based photocatalysts, allowing the isolation of 14 new compounds in up to 86% yield. Control experiments and computational studies revealed that the reaction proceeds through a Michael-type 1,4-addition of a trifluoromethyl radical, followed by a proton transfer step.
View Article and Find Full Text PDFMethylthiolation reactions are usually explored to access organosulfur compounds using methanethiol, an extremely flammable and toxic compound. Herein, methylthiomethyl esters were successfully applied as novel methylthiolation reagents in a low cost, transition-metal-free methodology. These reagents allowed the methylthiolation of a wide scope of chalcones, acyl ester derivatives and Morita-Baylis-Hillman acetates with good group tolerance, affording the methylthiolated products in moderate to excellent yields.
View Article and Find Full Text PDFA novel methodology for the 1,1-dichlorocyclopropanation of dicarbonyl conjugated olefins was described. The developed protocol is simple and uses readily accessible starting materials, allowing the isolation of the desired adducts in moderate to excellent yields (up to 99 %). Furthermore, the reaction tolerated scale up to the gram scale; thus highlighting the synthetic potential of this transformation.
View Article and Find Full Text PDFThe theoretical-guided evaluation of the Steglich rearrangement of azlactones and isoxazolones allowed the determination of the reactivity patterns in these heterocycles, including the factors that drive the regioselectivity toward both possible sites. These results allowed the first experimental report on the regioselective Steglich rearrangement of isoxazolones, affording the nitrogen- or carbon-acyloxy adducts.
View Article and Find Full Text PDFThe first report of the preparation of symmetric and nonsymmetric diaminotruxinic derivatives through the photoredox [2 + 2] cycloadditions of Erlenmeyer azlactones is described, affording the desired compounds in high regio- and diastereocontrol (only head-to-head coupling). Mechanistic studies by DFT suggest that the reaction proceeds through a neutral photocatalytic pathway.
View Article and Find Full Text PDFTuberculosis is an infectious disease with high incidence and growing drug-resistant rates. In an attempt to develop new antitubercular agents, 35 compounds were synthesized, most of them bearing a carbamate and enantiopure amino acid moiety. These compounds had their activity evaluated toward a Mycobacterium tuberculosis strain (ATCC 27294) and cytotoxicity against fibroblast MRC-5 cells (ATCC CCL-171).
View Article and Find Full Text PDFAzlactones are versatile heterocycles employed in a diversity of transformations; the main drawback of these cycles consists in the epimerization of the α-carbonyl stereocenter during its preparation. We hereby present a theoretical study to explain how the racemization occurs. Two hypotheses were investigated: the keto-enol tautomerism and the base-mediated racemization, through an enolate intermediate.
View Article and Find Full Text PDFA novel Brønsted base system for the diastereoselective dimerization of azlactones using trichloroacetate salts and acetonitrile has been developed. Desired products were obtained in good yields (60-93%) and with up to >19:1 dr after one hour of reaction. Additionally, the relative stereochemistry of the major dimer was assigned as being , by X-ray crystallographic analysis.
View Article and Find Full Text PDFBiometals
December 2017
This article has been corrected. One of the author names was given incorrect. Please find in this erratum the correct author name: "Heloiza Diniz Nicolella" that should be regarded as final by the reader.
View Article and Find Full Text PDFBiometals
December 2017
Novel lipophilic gold(I) complexes containing 1,3,4-oxadiazol-2-thione or 1,3-thiazolidine-2-thione derivatives were synthesized and characterized by IR, high resolution mass spectrometry, and H, C P NMR. The cytotoxicity of the compounds was evaluated considering cisplatin and/or auranofin as reference in different tumor cell lines: colon cancer (CT26WT), metastatic skin melanoma (B16F10), breast adenocarcinoma (MCF-7), cervical carcinoma (HeLa), glioblastoma (M059 J). Normal human lung fibroblasts (GM07492-A) and kidney normal cell (BHK-21) were also evaluated.
View Article and Find Full Text PDFAn organocatalytic protocol, employing the commercially available EDC as coupling agent, has been developed for the preparation of dual-protected amino acid derivatives without epimerization. This methodology was then applied to different Boc-amino acid and amine derivatives in moderate to excellent isolated yields. In addition, racemization-free Boc deprotection was also demonstrated.
View Article and Find Full Text PDFAzlactones (also known as oxazolones) are heterocycles usually employed in the stereoselective synthesis of α,α-amino acids, heterocycles and natural products. The versatility of the azlactone scaffold arises from the numerous reactive sites, allowing its application in a diversity of transformations. This review aims to cover classical and recent applications of oxazolones, especially those involving stereoselective processes.
View Article and Find Full Text PDFIn continuation of our efforts to find new antimicrobial compounds, series of fatty N-acyldiamines were prepared from fatty methyl esters and 1,2-ethylenediamine, 1,3-propanediamine or 1,4-butanediamine. The synthesized compounds were screened for their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and for their antifungal activity against four species of Candida (C. albicans, C.
View Article and Find Full Text PDFWe report in this work the preparation and in vitro antimicrobial evaluation of novel amphiphilic aromatic amino alcohols synthesized by reductive amination of 4-alkyloxybenzaldehyde with 2-amino-2-hydroxymethyl-propane-1,3-diol. The antibacterial activity was determined against four standard strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa) and 21 clinical isolates of methicillin-resistant Staphylococcus aureus. The antifungal activity was evaluated against four yeast (Candida albicans, Candida tropicalis, Candida glabrata and Candida parapsilosis).
View Article and Find Full Text PDF