Saturated N-heterocycles are prevalent in biologically active molecules and are increasingly attractive scaffolds in the development of new pharmaceuticals. Unlike their aromatic counterparts, there ...are limited strategies for facile construction of substituted saturated N-heterocycles by convergent, predictable methods. In this Synopsis, we discuss recent advances in the synthesis of these compounds, focusing on approaches that offer generality and convenience from widely available building blocks.
Interest in saturated N-heterocycles as scaffolds for the synthesis of bioactive molecules is increasing. Reliable and predictable synthetic methods for the preparation of these compounds, especially ...medium-sized rings, are limited. We describe the development of SnAP (Sn amino protocol) reagents for the transformation of aldehydes into seven-, eight- and nine-membered saturated N-heterocycles. This process occurs under mild, room-temperature conditions and offers exceptional substrate scope and functional-group tolerance. Air- and moisture-stable SnAP reagents are prepared on a multigram scale from inexpensive starting materials by simple reaction sequences. These new reagents and processes allow widely available aryl, heteroaryl and aliphatic aldehydes to be converted into diverse N-heterocycles, including diazepanes, oxazepanes, diazocanes, oxazocanes and hexahydrobenzoxazonines, by a single synthetic operation.
Substituted piperazines and morpholines are valuable structural motifs in biologically active compounds, but are not easily prepared by contemporary cross-coupling approaches. In this report, we ...introduce SnAP reagents for the transformation of aldehydes into N-unprotected piperazines and morpholines. This approach offers simple, mild conditions compatible with aromatic, heteroaromatic, aliphatic, and glyoxylic aldehydes and provides mono- and disubstituted N-heterocycles in a single step.
It's a SnAP! The transformation of aldehydes into N‐unsubstituted 3‐thiomorpholines provides a convenient alternative to metal‐catalyzed cross‐coupling reactions, which are generally unsuited to the ...functionalization of saturated N‐heterocycles. A copper‐mediated radical cyclization is the key to the mild conditions, high functional group tolerance, and broad substrate scope offered by these reagents.
Mixed acetals and organotrifluoroborates undergo BF3·OEt2-promoted cross-couplings to give dialkyl ethers under simple, mild conditions. A survey of reaction partners identified a hydroxamate leaving ...group that improves the regioselectivity and product yield in the BF3·OEt2-promoted coupling reaction of mixed acetals and potassium alkynyl-, alkenyl-, aryl- and heteroaryltrifluoroborates to access substituted dialkyl ethers. This leaving group enables the reaction to proceed rapidly under mild conditions (0 °C, 5–60 min) and permits reactions with electron-deficient potassium aryltrifluoroborates that are less reactive with other acetal substrates. A study of the reaction mechanism and characterization of key intermediates by NMR spectroscopy and X-ray crystallography identified a role for the hydroxamate moiety as a reversible leaving group that serves to stabilize the key oxocarbenium intermediate and the need for a slight excess of organodifluoroborane to serve as a catalyst. A secondary role for the boron nucleophile as an activating ligand was also considered. These studies provide the basis for a general class of reagents that lead to dialkyl ethers by a simple, predictable cross-coupling reaction.
The main protease 3CL
pro
is one of the potential targets against coronavirus. Inhibiting this enzyme leads to the interruption of viral replication. Chalcone and its derivatives were reported to ...possess the ability to bind to 3CL
pro
protease in the binding pocket. This study explored an in-house database of 269 chalcones as 3CL
pro
inhibitors using in silico screening models, including molecular docking, molecular dynamics simulation, binding free energy calculation, and ADME prediction.
C264
and
C235
stand out as the two most potential structures. The top hit compound
C264
was with the Jamda score of −2.8329 and the MM/GBSA binding energy mean value of −28.23 ± 3.53 kcal/mol, which was lower than the reference ligand. Despite the lower mean binding energy (−22.07 ± 3.39 kcal/mol), in-depth analysis of binding interaction suggested
C235
could be another potential candidate. Further, in vitro and in vivo experiments are required to confirm the inhibitory ability.
Lichens produce secondary metabolites that have many pharmaceutical activities such as antimicrobial, antioxidant, antiviral, anticancer, antigenotoxic, anti-inflammatory, analgesic and antipyretic ...activities. However, there is limited research on their efflux pump inhibitory activities. Twelve phytochemicals were isolated from
, and their activity of AcrAB-TolC efflux pump inhibition was evaluated. Four potential compounds, which are diffractaic acid
, 8' -
- methylstictic acid
, 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 2,4-dimethoxy-3,6-dimethylbenzoate (
and 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 2-hydroxy-4-methoxy-3,6-dimethylbenzoate
, were found by virtual screening using pharmacophore and 2D-QSAR model. Compound
exhibited AcrB inhibition activity
with an accumulation H33342 percentage compared with untreated control of 202% at a concentration of 50 µM and increased the antibacterial activity of levofloxacin by four-fold at a concentration of 200 µM. By molecular docking and molecular dynamics (MD) simulation, the binding affinity of depside and depsidone derivatives to AcrB was also clarified. Despite the poor docking score to the AcrB binding site, compound
was the most stable among the four complexes at 20 ns of MD simulation. The analysis of long MD at 100 ns indicated that compound
interacts strongly with the residues in the distal pocket, creating a stable complex with
of
kcal.mol-1. According to the ADMETlab 2.0 web server's predictions of pharmacokinetics and toxicities, compound
has the potential for drug development.Communicated by Ramaswamy H. Sarma.
Current in vitro pancreatic lipase inhibitor screenings are based on previous spectrophotometric lipase assays. Nevertheless, they are with little evaluation of assay conditions. This study focuses ...on the impacts of experimental factors on enzyme activity in the assay with p-nitrophenyl palmitate as substrate by monitoring their effects on the hydrolysis rates. On the results, experimental conditions for lipase inhibitory assay were proposed. Notably, 5 mM sodium deoxycholate as emulsifier not only maintains the assay homogeneity but also enhances lipase activity. Organic co-solvents to dissolve organic inhibitors including DMSO, EtOH, MeOH, IPA, AcCN 0–30% (v/v) was found well tolerated by the enzyme. With 10% (v/v) glycerol, lipase solutions can be stored at –20°C for up to one month without significant loss of activity. The results reported here provide researchers the assay condition sets in which most inhibitors can be dissolved, and lipase activity is not severely affected. This could accelerate the rational development of novel lipase inhibitors.
Die Umwandlung von Aldehyden in N‐unsubstituierte 3‐Thiomorpholine bildet eine einfache Alternative zu metallkatalysierten Kreuzkupplungen, die zur Funktionalisierung gesättigter N‐Heterocyclen im ...Allgemeinen ungeeignet sind. Eine kupfervermittelte radikalische Cyclisierung ist der Schlüssel für die milden Bedingungen, die hohe Verträglichkeit mit funktionellen Gruppen und den großen Substratbereich, den diese Reagentien bieten.
Then, this purified cellulose was co-polymerized by the addition of acrylic acid and ammonium persulfate in the presence of N,N-methylenebisacrylamide as crosslinker to form a cellulose-based ...hydrogel for the removal of hexavalent chromium (Cr(VI)) from wastewater. Here, the impact of various parameters, such as pH, contact time, material dosage, and initial solution concentration, on the adsorption capacity of the hydrogel for Cr(VI) ions is systematically investigated. The experimental findings revealed that the highest adsorption capacity for the treatment of Cr(VI)-containing water reached 1.1 mg Cr(VI)/g at pH 1, contact time of 120 min, and the initial concentration in the aqueous solution of 10 mg/L for an applied adsorbent dosage of 0.2 g. In addition, the equilibrium adsorption data agreed well with the Langmuir isotherm and the maximum adsorption amount was 4.14 mg Cr(VI)/g. Additionally, this material demonstrated good reusability, supporting the notion that it can be efficiently regenerated for multiple uses, a crucial factor for its practical application towards reducing the environmental impact and increasing its economic value.
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