Organic & Biomolecular Chemistry最新文献

Disulfide bonds are essential in protein folding, cellular redox balance, materials science, and drug development. Despite existing synthetic methods, the efficient and selective synthesis of unsymmetrical disulfides remains challenging. This review highlights innovative approaches in visible light photocatalysis, including decarboxylation, deoxydisulfidation of alcohols, and direct C-H disulfidation, showcasing broad substrate applicability and functional group tolerance under mild conditions. Additionally, it explores transition metal-catalyzed systems with copper, nickel, palladium, chromium, Iridium, Rhodium molybdenum, and scandium, offering effective strategies for unsymmetrical disulfide bond formation and late-stage functionalization of complex molecules through reductive coupling, selective oxidation, and novel insertion reactions.

An efficient and operationally simple photochemical method has been demonstrated under transition metal-free, photocatalyst-free, and oxidant-free conditions. In recent times, diaryliodonium salts have become one of the most popular arylating sources under photoinduced conditions. Herein, we developed a visible light induced arylation of heterocycles using an EDA complex that is formed in situ from 2,6-lutidine and diaryliodonium triflate. Under light irradiation, the EDA complex generates the aryl radical that undergoes addition with 2-oxo-2H-chromene-3-carbonitriles via an SET process. This method serves as an effective tool to access biologically active and pharmaceutically relevant coumarin scaffolds.

Many C-glycosides are found in natural products, drugs and small molecular probes. Herein, we report the synthesis of C-glycosides by the [Au]/[Ag]-catalysed activation of ethynylcyclohexyl glycosyl carbonate donors. This mild, catalytic, fast and high yielding protocol enables the synthesis of a diverse array of C-glycosides that were otherwise challenging to synthesize.

A silver-mediated cascade trifluoromethylthiolation/cyclization of unactivated alkenes has been investigated. This strategy employs AgSCF₃ as the trifluoromethylthiolating reagent to obtain a variety of useful trifluoromethylthiolated tricyclic imidazol derivatives in reasonable yields. Preliminary mechanistic studies indicate that the present reaction takes place via a radical process. This method is distinguished by its atom economy, wide functional group compatibility, operational simplicity and product diversity.

We have synthesized two sialic acid derivatives substituted with an ortho-nitrobenzyl alcohol (o-NBA) group that can undergo light-mediated conjugation with primary amines at their 5- or 9-carbon position. The o-NBA derivatives were shown to react with multiple lysine residues of human serum albumin (HSA) when exposed to 365 nm light irradiation within 10 min. The resulting sugar conjugates were characterized by mass spectroscopy and used for fluorescence-based cell imaging.

A K₂CO₃-promoted tandem ring-opening/ring-closing of N-alkynyl-2-oxazolidinones has been described, affording 2-oxazolines in 42-99% yields without column chromatography isolation. This operationally simple reaction proceeds under ambient conditions without a transition-metal catalyst and an external oxidant and can be applied for the late-stage functionalization of biologically active compounds.

An efficient method to construct 4-phenyl-4-hydroxyquinazolin-2-thiones 3via solvent-free and catalyst-free addition of o-aminobenzophenone 1 with aryl isothiocyanates 2 under thermal conditions has been developed, providing new congested 4-phenyl-4-hydroxyquinazolin-2-thiones 3 in practically quantitative yields via simple purification by filtration/recrystallization. Extension of these conditions to o-aminoacetophenone 4 in place of o-aminobenzophenone 1 led to 4-methylenequinazoline-thione 5 as a result of a subsequent dehydration reaction.

Multidrug-resistant bacterial infections continue to be a rising global health concern. Herein, we describe the development of a novel class of 3-substituted benzoazepinedione derivatives with promising antibacterial activity. The pivotal compound, benzoazepinedione carboxylate 9, represents a highly electrophilic Michael acceptor, enabling divergent access to a wide range of thia-, aza-, oxa-, and phospha-Michael adducts. Notably, most prepared compounds exhibited potent antibacterial activity against both drug-susceptible and drug-resistant strains of Staphylococcus aureus (MIC₉₀ of up to 2 μg mL^-1). The cytotoxicity assessment in the VERO6 cell line revealed that thia-adduct 10d (IC₅₀ of 36.5 μg mL^-1) exhibits lower toxicity compared to its parent electrophile 9 (IC₅₀ of 14.3 μg mL^-1), which is in agreement with the hypothesis of covalently modified prodrugs. Additionally, stability studies of the prepared compounds in CD₃OD and a DMSO-PBS mixture confirmed that thia-Michael adducts 10 are stable under neutral conditions while dynamic under mildly basic conditions. Moreover, 3D reconstructed tissue models (human lung epithelial EpiAirway™ and a human small intestine model) did not exhibit a viability decrease below 80% of the untreated control at all concentrations tested, indicating tolerance to higher concentrations of potential drugs and prodrugs.

We report a two-step one-pot synthesis of the 2,6-diarylmorpholin-3-one core based on the Ugi reaction of 2-oxoaldehyde with 2-hydroxycarboxylic acid, a primary amine and tert-butyl isocyanide followed by a triflic acid-promoted intramolecular condensation accompanied by the loss of the isocyanide-originated amide moiety. The overall transformation proceeds with complete retention of stereoconfiguration at the 2-hydroxycarboxylic acid-derived chiral center, allowing the target morpholin-3-ones to be obtained in an enantiopure form. Subsequent double bond hydrogenation and amide reduction allow the degree of unsaturation to be reduced, providing a convenient entry to the cis-2,6-diphenylmorpholine motif.

Asiatic acid (AA) is a naturally occurring pentacyclic triterpene isolated from Centella asiatica and has various biological effects, most notably anticancer effects. While numerous investigations have demonstrated the possible mechanism underlying AA's anticancer action, the precise protein target of AA remains unclear. In this study, the protein target of AA in HepG2 hepatoma cells was identified using the AfBPP-based chemoproteomic approach. Initially, a diazirine and alkyne group modified AA photoaffinity probe was synthesized. Then, using mass spectrometry analysis, 13 putative target proteins were identified with high confidence. Combined with the competition bands in in situ fluorescence scanning, the α-tubulin alpha-1B chain (TUBA1B) was identified as the target protein of AA. Subsequently, the direct interaction between AA and TUBA1B was verified by surface plasmon resonance, pull-down and cellular thermal shift experiments, drug affinity responsive target stability assay, and molecular docking. This research will offer fresh perspectives on how AA prevents liver cancer at the molecular level.