Piperidines are privileged scaffolds in medicinal chemistry because of their frequent occurrence in biologically active natural products and therapeutic agents. Construction of molecular hybrids combining natural-like pyrazolyl-piperidinone and 8-aminoindolizidine fragments...
In the present communication, a novel synthetic approach to allomaltol-containing 1,4-diketones has been developed. The strategy relies on oxidative enolate coupling of the corresponding ketones and enables diastereodivergent synthesis controlled by the nature of the base. Depending on the base employed, two distinct diastereomers (meso and racemic forms) are selectively obtained from the same starting material. Their interconversion under various conditions was demonstrated, indicating thermodynamic control of the stereochemical outcome. The structures of both diastereomers were unambiguously established via X-ray analysis. Furthermore, the synthesized 1,4-diketones serve as versatile precursors for a series of novel tetrasubstituted furan derivatives.
An inexpensive copper(II) bromide-catalyzed cross-dehydrogenative coupling/Kornblum oxidation/formal decarbonylation of N-substituted/unsubstituted quinoxalinones in DMSO is reported. It has offered a new technique for the cleavage of C(CO)-C(CO) bond under base- and...
Two complementary oxidative [3+2] cyclization protocols were developed for the synthesis of sulfur-containing benzimidazo[2,1-b]thiazole derivatives from enaminones and 2-mercaptobenzimidazole. The first method exploits visible-light-induced activation through an electron donor-acceptor (EDA)...
We report a highly enantioselective organocatalyzed Michael addition of N-substituted 3-chlorooxindoles to 1,1-bis(arylsulfonyl)ethylenes. With a readily available quinine-derived catalyst under mild conditions, this reaction delivers chiral 3,3-disubstituted oxindoles in high yields (up to 93%) and enantioselectivities (up to 92% ee). The protocol features broad substrate scope, tolerating a variety of substituents at the 4- to 6-positions of the oxindole ring, as well as diverse N-aryl or N-alkyl groups. Furthermore, the resulting adducts undergo facile intramolecular SN2-type cyclization to give spirocyclopropane-fused oxindoles with full retention of enantiomeric purity. A one-pot cascade variant is also demonstrated; notably, 3-bromooxindole delivers the spirocyclopropane product with 98% ee.
8-Arylxanthines have been extensively investigated due to their diverse biological activities. However, despite numerous studies focusing on their synthesis and biological effects, their fluorescence properties have remained largely overlooked. In this study, we demonstrate how the introduction of aromatic substituents can modulate and enhance the photophysical behavior of 8-arylxanthines, revealing their potential as fluorescent imaging tools. Taking into account the rapidly advancing applications of bioorthogonal chemistry, a series of click-active 8-arylxanthines bearing a propargyl functional group were designed and synthesized. Their photophysical and electrochemical properties were systematically evaluated. A lead compound (XN1) was identified that exhibited a high Stokes shift (65 nm) and fluorescence quantum yield (ΦF = 0.962), while showing no significant cytotoxicity across a range of cancer cell lines as well as healthy cells under the tested conditions. Our findings highlight the tunability of xanthine-based fluorophores and suggest that these derivatives hold significant promise for use in fluorescence-based imaging applications.
Horseradish peroxidase (HRP)-catalyzed oxidation of luminol is a cornerstone chemiluminescent reaction, proceeding through nitrogen extrusion to generate an electronically excited 3-aminophthalate species. Here we report that 3-indazolinones, a structurally related...
MicroRNAs (miRNAs) are crucial regulators in tumor development, so accurately detecting and imaging them in living cells is vital for early cancer diagnosis. However, their low levels inside cells and the complex cellular environment make traditional detection methods challenging. We developed a fluorescent sensing platform, ZIF-8@SA@reporter, which combines DNAzyme catalytic cleavage with ZIF-8-mediated fluorescence quenching for sensitive detection and imaging of miRNA-21. ZIF-8 acts as a nanocarrier to efficiently load and deliver fluorophore-labeled substrates while quenching fluorescence to minimize background signals. When miRNA-21 is present, the DNAzyme is activated by Mg2+, cleaving the substrate and releasing the fluorophore, restoring fluorescence. This sensor has a linear detection range from 1 μmol L-1 to 10 pmol L-1, with the lowest experimentally detectable concentration of 1 pmol L-1. Live-cell imaging showed clear green fluorescence in MCF-7 and MKN-45 tumor cells, with stronger signals in MKN-45 cells due to higher miRNA-21 levels. This approach offers a reliable tool for early cancer diagnosis and monitoring of miRNA-related diseases.
Correction and removal of expression of concern for 'Total synthesis of the natural product EBC-329' by Raju S. Thombal et al., Org. Biomol. Chem., 2015, 13, 9485-9491, https://doi.org/10.1039/C5OB01276G.
The unprecedented C(sp2)-H functionalization of ethylidenemalonate with internal alkynes was discovered, leading to substituted vinylcyclopentanes as trans,trans-isomers (dr > 15 : 1). The experiment with deuterated ethylidenemalonate showed that the formation of substituted vinylcyclopentane is accompanied by a 1,2-hydride shift and mono-γ-C-H insertion into the internal alkyne.
A cationic AIE photosensitizer TTPy-PTSA preferentially accumulates in the mitochondria of HUVECs and generates ROS efficiently upon irradiation, triggering caspase-3-mediated apoptosis. It exhibits potent anti-angiogenic photodynamic activity in vitro and...
We report the water-soluble macrocycle ExBP3C, which binds 20 guests to form well-defined 1 : 1 complexes, with association constants in the range of 102-105 M-1. NMR studies, titration experiments and theoretical calculations clearly uncovered the binding stoichiometry, affinities, and complexation modes. This host holds promise for applications in neurotransmitter regulation, photosensitizer delivery, and antibacterial systems.
The development of citrullination detection methods has largely been driven by a fundamental chemical problem: distinguishing citrulline from its precursor arginine. Protein citrullination is a biologically relevant modification catalyzed by the peptidyl arginine deiminase (PAD) enzyme family. Dysregulated PAD activity has been implicated in several major human diseases, including rheumatoid arthritis, neurodegeneration, and cancer. In practice, studying this modification has long been difficult because the two amino acids, citrulline and arginine, are so chemically similar that most chemical reagents struggle to distinguish between them. This review highlights the evolution of citrullination detection, from colourimetric assays requiring harsh acidic conditions, through fluorescent probes that increased sensitivity, and to newer chemistries that can label citrulline at neutral pH. Alongside these citrulline-directed strategies, we also cover complementary approaches for profiling PAD enzyme activity, including antibody-based and activity-based protein profiling, as well as fluorogenic substrate assays.
Herein, we disclose an asymmetric alkylation of an α-C(sp3) bond of glycine derivatives proceeding through synergistic copper/photoredox catalysis. It is worth noting that this work represents the first example of an asymmetric transformation induced by the challenging 1,2-HAT process of amidyl radicals. This protocol is characterized by good yields, moderate to excellent enantioselectivities and simple operation procedures, providing an attractive strategy for the synthesis of biologically valuable α,β-diamino acids.
A new nitrosylation reaction for pyrroles, featuring tert-butyl nitrite as a mild nitrosylation agent, has been developed. Application to a variety of diaryl-substituted pyrroles resulted in moderate to good yields with significant improvement, in comparison to previous methods, for pyrroles featuring aryl groups appended with electron-donating groups. Isolation and characterisation of a nitrosopyrrole featuring tert-butyl functionality on the pyrrole ring was achieved in excellent yield, while attempts to nitrosylate other alkyl-functionalised pyrroles yielded trace amounts of promising oxime-containing products.
A visible-light-driven nickel-catalyzed cross-electrophile coupling of aryl halides with alkyl iodides has been developed using 9-fluorenone (FLN) as an inexpensive organic photosensitizer. The readily available FLN/diisopropylethylamine system enables C(sp2)-C(sp3) bond formation in moderate to high yields under mild conditions. The reaction accommodates aryl iodides, bromides, and chlorides as well as a range of primary and secondary alkyl iodides, while avoiding precious-metal photocatalysts and stoichiometric metal reductants. This study establishes FLN as a practical photosensitizer for nickel-catalyzed reductive cross-coupling.
A series of unsymmetrical 1-(p-tolulyl)-5,6-di(p-tolyl)-10-(acyl)-dipyrroethenes were synthesized in two steps starting with 5,6-di(p-tolyl)dipyrroethene. In the first step, 5,6-di(p-tolyl)dipyrroethene was subjected to the Grignard reaction with 4-methylbenzoyl chloride to afford 1-(p-tolulyl)-5,6-di(p-tolyl)dipyrroethene, which was then subjected to another Grignard reaction with different aryl acid chlorides such as benzoyl chloride, 4-iodobenzoyl chloride, 4-methoxybenzoyl chloride, 2-thiophene carbonyl chloride and 2-furoyl chloride to afford unsymmetrical 1-(p-tolulyl)-5,6-di(p-tolyl)-10-(acyl)-dipyrroethenes in 67-75% yields. The unsymmetrical 1,10-diacyl-5,6-di(p-tolyl)dipyrroethenes were in situ reduced by NaBH4 to corresponding unsymmetrical diols and condensed with pyrrole under mild acid catalysed conditions followed by chromatographic purification to afford the first examples of A3B type meso-tetraaryl triphyrin(2.1.1)s in 16-19% yields. The unsymmetrical A3B type meso-tetraaryl triphyrin(2.1.1)s were thoroughly characterized and studied by HRMS, NMR, X-ray crystallography for one of the triphyrins, absorption and fluorescence spectroscopy, cyclic voltammetry and theoretical techniques. Furthermore, the utility of mono-functionalized A3B type meso-tetraaryl triphyrin(2.1.1) is demonstrated through the synthesis of a covalently linked ferrocene-triphyrin(2.1.1) dyad. The preliminary studies showed a possibility of photoinduced electron transfer from the ferrocene moiety to the triphyrin(2.1.1) macrocycle.
Glycosides are crucial structural motifs in drug discovery and biology due to their enhanced metabolic stability and resistance to enzymatic hydrolysis compared to their O-glycoside counterparts. The synthesis of these...
The synthesis of chromenonitriles remains largely underexplored, primarily due to the limited availability of suitable substrates and the generally unsatisfactory yields of existing methods. Herein, we report a new method...
Polyhydroxy containing compounds, in particular those derived from monoterpenoids, have attracted attention as biologically active compounds, but a key limitation in their synthesis is the need for regio- and stereoselective hydroxylation. Here, the synthesis of two dihydroxy derivatives and potential metabolites of the antiparkinsonian agent Prottremine, which is a monoterpenoid diol with a para-menthene scaffold, was carried out using an epoxy ester-orthoester rearrangement as the key step. The isomerization of epoxyacetate derivative of Prottremine to corresponding orthoester proceeded stereoselectively, as a result, two new stereoisomeric tetraols were obtained in yields of 22% and 3%. Using a similar approach directly and in combination with the Mitsunobu reaction, three stereoisomeric triols based on (-)-isopulegol and (+)-neoisopulegol were synthesized in yields ranging from 13% to 36%, thus demonstrating the potential to expand the approach to other compounds. Isomerization of the epoxyacetate derivative in the presence of superacids was accompanied by aromatization of cyclohexene ring with the formation of the dioxolane cation, which then, upon longer storage at room temperature, was completely converted into a mixture of protonated ketones, one of which was a dimeric form (dication).
