Organic & Biomolecular Chemistry最新文献

Optically active indolines are valuable structural motifs present in numerous naturally occurring and biologically active molecules. Although several methodologies have been reported in the literature for the synthesis of chiral indolines, many of them rely on the hydrogenation of indoles using expensive metal catalysts. In this report, a copper(II)-catalysed enantioselective (4 + 1) cycloaddition of aza-o-quinone methides (aza-o-QMs) with bromomalonates to access indolines is described. The reactive aza-o-QMs are generated in situ from simple and easily accessible 2-chloromethyl arylsulfonamides under basic conditions, and subsequently undergo cyclization with the in situ formed bromomalonate anion to deliver diverse chiral indoline derivatives in up to 69% yields and 96 : 4 er. Scale up and further derivatizations occurred without erosion of enantioselectivity, showing the robustness of this methodology.

A metal-free, chemoselective TfOH-mediated union of α-diazo carbonyl compounds and indolin-2-thiones to access functionalized indoles has been disclosed. Interestingly, indolin-2-thiones treated with α-diazo esters delivered indolyl thioethers through formal S-H insertion, and α-diazo ketones provided fused hybrid heterocyclic systems, thiazolo[3,2-a]indoles, through a cascade process involving S-H insertion, cyclization, and dehydration. Furthermore, these newly synthesized compounds showed promising anti-cancer activities against breast cancer and prostate cancer cell models.

A straightforward and efficient strategy has been established for the synthesis of cinnamic esters and cinnamic acids through the reaction of acrylic anhydride and aryl diazonium salts in a variety of solvents. The reaction to obtain cinnamic esters proceeds smoothly at room temperature in the presence of palladium acetate. In contrast, the formation of cinnamic acids requires basic conditions and is effectively achieved using K₂CO₃ at 80 °C in a DMF/H₂O solvent system. All the desired products were obtained in good yield. The approach offers several notable advantages, including operational simplicity, readily available and inexpensive starting materials, mild reaction conditions, and good product yields. The antioxidant potential of the synthesized cinnamic esters was assessed through radical scavenging activity (RSA) assays, along with their inhibitory effects on amyloid-β (Aβ) aggregation. Most compounds displayed a satisfactory range of RSA, while a subset of the derivatives exhibited moderate Aβ aggregation inhibitory activity.

Metal-peptide superhelices formed from 12/10-helical β-peptide foldamers exhibit programmable hierarchical assembly. A single metal-coordinated superhelix organizes into distinct parallel or antiparallel arrangements without conformational distortion. This adaptability arises from a minimized macrodipole and dynamic folding propensity, establishing general design principles for peptide-based supramolecular materials.

Diarylethenes provide light-controllable generation of reactive species (such as Brønsted and Lewis acids) to trigger various processes with high spatial and temporal resolution. At the same time, the opposite light-induced deactivation has not been developed yet. A promising way to achieve such controllable "removal" of acidity is the introduction of a carboxyl group at one of the reactive carbons. To address this issue, we studied the irreversible photoreactions of the corresponding substrates in the diphenylethene and phenyloxazolylethene series. Indeed, exposure to UV light led to the irreversible elimination of the carboxyl group during transformation to phenanthrene or naphthalene products. The efficiency of this reaction, competing processes, and the reactivity of the related esters and salts are discussed. Our results show that the carboxyl group (or its derivatives) can serve as the leaving group in the photochemical reactions of diarylethenes, thus providing "photoswitching-off" of acidity.

A series of N-tert-butoxycarbonyl-protected isatin 3-imines underwent an unexpected C-2 selective addition reaction with Grignard reagents, affording 3-imino-2-phenethylindolin-2-ols. The protecting group plays a role in this observed chemoselectivity, with N-benzyl and N-p-methoxybenzyl-protected isatin 3-imines undergoing C-3 addition under Grignard reaction conditions, affording 3-amino-3-phenethylindolin-2-ones. Both C-2 and C-3 addition products were assessed for antiplasmodial activity in vitro, with four compounds displaying activity in the sub-micromolar range against both drug-sensitive and drug-resistant Plasmodium falciparum strains.

Sesquiterpenoid scaffolds such as the eudesmane-type linderolides and elemanolide-type isogermafurenolides remain synthetically challenging despite their structural interest and documented biological activities. While prior studies have addressed the parent isogermafurenolide through racemic and asymmetric approaches, the linderolides and the 15-acetoxy isogermafurenolide congeners have not been accessed synthetically. Herein, we report the first total synthesis of the ent-linderolide E, ent-15-hydroxy isogermafurenolide (ent-linderolide F), and ent-15-acetoxy isogermafurenolide, along with a concise synthesis of ent-isogermafurenolide. The route features four key transformations: a Tanabe lactonisation for lactone formation, a site-selective allylic oxidation, a Luche reduction, and a ring-closing metathesis constructing the eudesmane framework. Additionally, single-crystal X-ray diffraction analysis of synthetic material establishes a revised structural assignment for natural linderolide E.

Iron-catalyzed radical reactions provide a powerful and sustainable approach in organic synthesis, offering cost-effective and environmentally benign alternatives to precious-metal catalysts. Its redox versatility allows controlled radical generation under mild conditions, enabling diverse transformations. Iron activates C-X bonds via halogen abstraction or single-electron transfer (SET) and functions as a bifunctional Lewis acid through Fe-σ and Fe-π interactions, further broadening its reactivity. These features have expanded applications in pharmaceuticals, natural products, and functional materials. Coupling iron catalysis with photoredox methods enhances both reaction scope and sustainability. This review surveys recent advances in cross-coupling, C-H functionalization, cyclization, decarboxylation, amination, and heterocycle synthesis, organized by radical generation strategies, and concludes with perspectives on future developments.

Quinolines, dihydrofuroquinolines, and quinoline-fused lactones are privileged scaffolds found in numerous natural products and bioactive molecules. We report a novel and efficient Cu-catalyzed intermolecular oxidative imino Diels-Alder (Povarov-type) cyclization of (2-propargyloxy)acetaldehydes with aromatic amines for the synthesis of dihydrofuro[3,4-b]quinolines. This method employs inexpensive and readily available substrates and proceeds through sequential imine formation, intramolecular [4 + 2] cycloaddition, and oxidative aromatization, while tolerating a broad range of functional groups. Oxone acts as a green and cost-effective oxidant, affording the desired products in high yields. Furthermore, subsequent benzylic oxidation enables efficient conversion of dihydrofuroquinolines into quinoline-fused lactones, which are valuable intermediates in natural product synthesis.

A facile Zinc(II)-catalyzed cascade [4 + 2] cyclization of enynones with anthranils was developed to afford a series of 2-furanyl quinolines derivatives with various substituents in up to 91% yield via ring-opening/tandem cyclization. Mechanistic studies indicated that enaminone is an important intermediate, and furylcarbene was employed as a novel 2C synthon unit in this reaction. This protocol is characterized by high step economy, good functional group tolerance, simple operation, and a cheap zinc salt as the catalyst with low toxicity, and provides a new route for the synthesis of 2-furanyl quinolines with a variety of potential biomedical activities.