Synthesis and Biological Evaluation of New Dihydrofuro[3,2-b]piperidine Derivatives as Potent α-Glucosidase Inhibitors.

Inhibition of glycoside hydrolases has widespread application in the treatment of diabetes. Based on our previous findings, a series of dihydrofuro[3,2-b]piperidine derivatives was designed and synthesized from D- and L-arabinose. Compounds 32 (IC50 = 0.07 µM) and 28 (IC50 = 0.5 µM) showed significantly stronger inhibitory potency against α-glucosidase than positive control acarbose. The study of the structure-activity relationship of these compounds provides a new clue for the development of new α-glucosidase inhibitors.

Dess-Martin Periodinane-Mediated Oxidative Coupling Reaction of Isoquinoline with Benzyl Bromide.

Dess-Martin periodinane (DMP) is a broadly applicable oxidant in chemical synthesis. In this work, an efficient and convenient synthesis of N-substituted isoquinolinone derivatives mediated by DMP was achieved through the oxidative coupling reaction of functionalized isoquinoline with readily available benzyl bromide, which is a metal-free, mild, and practical method for synthesizing isoquinoline-1,3-dione or isoquinoline-1,3,4-trione derivatives in excellent yields. The H2O18-labeling experiment was performed to gain insight into the possible mechanism for this reaction.

New Monoterpene Glycoside Paeoniflorin Derivatives as NO and IL-1ß Inhibitors: Synthesis and Biological Evaluation.

Several monoterpene glycoside compounds were extracted from Paeonia lactiflora Pall. Among them, paeoniflorin, a water-soluble monoterpene glycoside found in the root of Paeonia lactiflora Pall, exhibits excellent antioxidant pharmacological functions. Initially, Sc(CF3SO3)3 was employed as the catalyst for paeoniflorin's dehydration and rearrangement reactions with alcohols. Subsequently, structural modifications were performed on paeoniflorin through a series of responses, including acetylation, deacetylation, and debenzoylation, ultimately yielding 46 monoterpene glycoside derivatives. The potential inhibitory effects on the pro-inflammatory mediators interleukin-1 beta (IL-1ß) and nitric oxide (NO) were assessed in vitro. The results revealed that compounds 29 and 31 demonstrated notable inhibition of NO production, while eight derivatives (3, 8, 18, 20, 21, 29, 34, and 40) displayed substantial inhibitory effects on the secretion of IL-1ß. Computational research was also undertaken to investigate the binding affinity of the ligands with the target proteins. Interactions between the proteins and substrates were elucidated, and corresponding binding energies were calculated accordingly. The findings of this study could provide valuable insights into the design and development of novel anti-inflammatory agents with enhanced pharmacological properties.

One-Pot Synthesis of 2-C-Branched Glycosyl Triazoles by Integrating 1,2-Cyclopropanated Sugar Ring-Opening Azidation and CuAAC Reaction.

A series of 2-C-branched glycosyl triazoles including triazole-tethered oligosaccharides and glycopeptides were synthesized in one pot from 1,2-cyclopropanated sugars or 2'-acetonyl-2-O-Ts-C-furanosides, NaN3, and alkynes using PEG-400 as a single solvent. Nucleophilic ring-opening azidation of 1,2-cyclopropanated sugars (or 2'-acetonyl group 1,2-migration-azidation of C-furanosides) obtained glycosyl azides, which upon reaction with alkynes under CuAAC conditions achieved glycosyl triazoles in good yields and high stereoselectivity without the need to change the solvent and isolate any intermediates.

Controllable transformation of indoles using iodine(III) reagent.

Herein, an efficient and highly functional group-compatible procedure for controllable transformation of indoles by the combination of phenyliodine bis(trifluoroacetate) (PIFA) with n-Bu4NCl·H2O (TBAC) was exploited. Through controlling the amount of PIFA and TBAC from one to three equivalents, 3-chloro-indoles, 3-chloro-2-oxindoles, and 3,3-dichloro-2-oxindoles were obtained, respectively, in satisfactory to excellent yields. The advantages of the protocol include mild conditions, facile process with short reaction time, high yields, satisfactory functional group tolerance, and the use of PIFA, which is an air- and moisture-stable promoter. The mechanism studies showed that the reaction may proceed through a halonium ion species-mediated halogenation-elimination-halogenation stepwise process.

Synthesis of N-Substituted Iminosugar C-Glycosides and Evaluation as Promising α-Glucosidase Inhibitors.

A series of N-substituted iminosugar C-glycosides were synthesized and tested for α-glucosidase inhibition. The results suggested that 6e is a promising and potent α-glucosidase inhibitor. Enzymatic kinetic assays indicated that compound 6e may be classified as an uncompetitive inhibitor. The study of structure-activity relationships of those iminosugars provided a starting point for the discovery of new α-glucosidase inhibitors.

Advances in Atroposelectively De Novo Synthesis of Axially Chiral Heterobiaryl Scaffolds.

Axially chiral heterobiaryl frameworks are privileged structures in many natural products, pharmaceutically active molecules, and chiral ligands. Therefore, a variety of approaches for constructing these skeletons have been developed. Among them, de novo synthesis, due to its highly convergent and superior atom economy, serves as a promising strategy to access these challenging scaffolds including C-N, C-C, and N-N chiral axes. So far, several elegant reviews on the synthesis of axially chiral heterobiaryl skeletons have been disclosed, however, atroposelective construction of the heterobiaryl subunits by de novo synthesis was rarely covered. Herein, we summarized the recent advances in the catalytic asymmetric synthesis of the axially chiral heterobiaryl scaffold via de novo synthetic strategies. The related mechanism, scope, and applications were also included.

A Novel Method to Construct 2-Aminobenzofurans via [4 + 1] Cycloaddition Reaction of In Situ Generated Ortho-Quinone Methides with Isocyanides.

A new approach for the synthesis of 2-aminobenzofurans has been described via Sc(OTf)3 mediated formal cycloaddition of isocyanides with the in situ generated ortho-quinone methides (o-QMs) from o-hydroxybenzhydryl alcohol. Notably, as a class of readily available and highly active intermediates, o-QMs were first used in the construction of benzofurans. This [4 + 1] cycloaddition reaction provides a straightforward and efficient methodology for the construction of 2-aminobenzofurans scaffold in good yield (up to 93% yield) under mild conditions.

Titanium Incorporation into Zr-Porphyrinic Metal-Organic Frameworks with Enhanced Antibacterial Activity against Multidrug-Resistant Pathogens.

This study uses metal-organic frameworks (MOFs) alone without any added antibacterial ingredients as the nonantibiotic agent for photodynamic therapy (PDT) of chronic wounds infected by multidrug-resistant (MDR) bacteria. Nanoparticles (NPs) of MOFs (PCN-224) are incorporated with titanium through a facile cation exchange strategy. The obtained bimetallic PCN-224(Zr/Ti) shows greatly enhanced photocatalytic performance for the generation of reactive oxygen species under visible light, which is responsible for the effective antibacterial activities. The PCN-224(Zr/Ti) NPs are loaded onto lactic-co-glycolic acid nanofibers to prepare a wound dressing, which shows high biocompatibility and minimal cytotoxicity. The wound dressing is efficient for PDT-based in vivo healing of the chronic wound infected by MDR bacteria. Most importantly, this work does not involve any additional antibacterial agents, which is facile, low cost, and in particular, greatly explores the potential of MOFs as a powerful nonantibiotic agent in PDT.

Direct and highly stereoselective synthesis of quinolizidine iminosugars promoted by l-proline-Et3N.

A mild and effective method for the synthesis of polyhydroxylated quinolizidine iminosugars is described. The Mannich-type reaction of iminosugar C-glycosides with aldehyde in the presence of l-proline-Et3N provides polyhydroxylated quinolizidine iminosugars, and desired products as the potential glucosidase inhibitors were obtained in good to excellent yields with excellent stereoselectivity.

Zn(OTf)2 promoted rearrangement of 1,2-cyclopropanated sugars with amines: a convenient method for the synthesis of 3-polyhydroxyalkyl-substituted pyrrole derivatives.

A rearrangement reaction of 1,2-cyclopropanated sugars with alkylamines or arylamines promoted by Zn(OTf)2 is described. The method offers a series of 3-polyhydroxyalkyl-substituted pyrrole derivatives with multiple chiral centers in moderate to excellent yields. The epimerization is achieved by inverting the stereochemistry at the free hydroxyl group of the resulting pyrrole, which would give access to many more possible stereoisomers.

Label-free colorimetric detection of cadmium ions in rice samples using gold nanoparticles.

A simple and label-free colorimetric method for cadmium ions (Cd(2+)) detection using unmodified gold nanoparticles (AuNPs) is reported. The unmodified AuNPs easily aggregate in a high concentration of NaCl solution, but the presence of glutathione (GSH) can prevent the salt-induced aggregation of AuNPs. When Cd(2+) is added to the stable mixture of AuNPs, GSH, and NaCl, Cd(2+) can coordinate with 4× GSH as a spherical shaped complex, which decreases the amount of free GSH on the surface of gold nanoparticles to weaken the stability of AuNPs, and AuNPs will easily aggregate in high-salt conditions. On the basis of the mechanism, we design a simple, label-free colorimetric method using AuNPs accompanied by GSH in a high-salt environment to detect Cd(2+) in water and digested rice samples.

A neighboring group participation strategy: direct and highly diastereoselective synthesis of 2-substituted and 2,2-bisubstituted perhydrofuro[2,3-b]pyran derivatives.

Treatment of methyl 2-C-formylmethyl-2-deoxy-ß-D-glucopyranoside (5) or methyl 2-C-acetylmethyl-2-deoxy-ß-D-glucopyranoside (1) with H2SO4­HOAc­Ac2O gave 2-acetoxyl-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]hexahydrofuro[2,3-b]pyran (6) and acetyl 2-C-acetylmethyl-2-deoxy-α-D-glucopyranoside (7) respectively, which were further reacted with nucleophiles in the presence of TMSOTf and offered a series of 2-substituted and 2,2-disubstituted perhydrofuro[2,3-b]pyran derivatives in high yield with excellent diastereoselectivity.

An environmentally benign protocol for the synthesis of sugar 1,2-orthoesters in poly(ethylene glycol) dimethyl ether (DMPE).

An environmentally benign procedure has been developed for the synthesis of sugar orthoesters using anhydrous sodium acetate in poly (ethylene glycol)dimethyl ether (DMPE). Various sugar orthoesers were prepared without using volatile organic solvent and quaternary ammonium salt. The sugar orthoesters were obtained in good to excellent yields.

Synthesis of Functionalized Tetrahydroquinoline Containing Indole Scaffold via Chemoselective Annulation of Aza-ortho-quinone Methide Precursor.

The chemoselective annulation of aza-ortho-quinone methide generated by in situ o-chloromethyl sulfonamide has been achieved with bifunctional acyclic olefin. This efficient approach provides access to the diastereoselective synthesis of functionalized tetrahydroquinoline derivatives containing indole scaffolds through the inverse-electron-demand aza-Diels-Alder reaction under mild reaction conditions with excellent results (up to 93% yield, > 20:1 dr). Moreover, this article realized the cyclization of α-halogeno hydrazone with electron-deficient alkene affording the tetrahydropyridazine derivatives, which had never been reported.

Stable fluorescent gold nanoparticles for detection of Cu2+ with good sensitivity and selectivity.

A simple and one-pot method for the synthesis of water-soluble, red-emitting, highly fluorescent gold nanoparticles has been reported using 11-mercaptoundecanoic acid (11-MUA) as the protecting group. We found that the fluorescent gold nanoparticles could selectively detect copper ions in aqueous solution, with a limit of detection of about 87 nM.

Boronic Acid-Decorated Multivariate Photosensitive Metal-Organic Frameworks for Combating Multi-Drug-Resistant Bacteria.

Metal-organic frameworks (MOFs) are promising photosensitized materials that have displayed great advantages in antibacterial application. However, their bactericidal activity is still limited by the ultrashort diffusion distance of biocidal reactive oxygen species (ROS). Herein, we integrate the bacterial-binding boronic acid ligand and photosensitized porphyrin into one single MOF, synergistically boosting antibiotic capability. The introduction of the boronic acid group with a closed physical gap makes multivariate MOFs more powerful for eradicating multi-drug-resistant (MDR) bacteria. The MOFs that are decorated with boronic acid possess antibacterial efficiencies (10-20 times) higher than those without the targeting ligand. Moreover, the MOFs exhibit excellent biocompatibility. They significantly decrease the inflammatory responses and accelerate the healing of chronic wounds infected with MDR bacteria (nearly 2 times faster). This work provides a strategy to develop multivariate MOFs that target bacteria, which will further inspire specific bacterial-binding therapy in the future.

Chemodivergent Synthesis of Aza-Heterocycles with a Quarternary Carbon Center via [4 + 1] Annulation between Azoalkenes and α-Bromo Carbonyl Compounds.

An efficient [4 + 1] annulation reaction between in situ generated azoalkene intermediates and α-bromocarbonyls has been established. A series of skeletally diverse aza-heterocycles with a functionalized quaternary center were obtained in up to 89% yield under mild conditions.

Stereoselective synthesis of 2-C-branched (acetylmethyl) oligosaccharides and glycoconjugates: Lewis acid-catalyzed glycosylation from 1,2-cyclopropaneacetylated sugars.

1,2-Cyclopropaneacetylated sugars as glycosyl donors reacted with a series of glycosyl acceptors (monosaccharides, amino acids, and other alcohols) in the presence of Lewis acid to produce oligosaccharides and glycoconjugates containing 2-C-acetylmethylsugars. Galactosyl donor gave good to excellent α-selectivities with TMSOTf as a catalyst, whereas galactosyl donor offered moderate to good ß-selectivities when BF(3)·Et(2)O was used as a catalyst. However, glucosyl donors produced ß-exclusive selectivity under both conditions. The stereoselectivities of glycosylation depend on the reactivity of donor sugars and Lewis acid catalyst, which effectively dictated the glycosylation pathways. The evidence suggests that galactosyl donors (e.g., 7) can undergo S(N)1 pathway with a strong Lewis acid (TMSOTf) and S(N)2 pathway under BF(3)·Et(2)O, whereas the glucosyl donors (e.g., 8 and 10) followed S(N)2 pathway. The stereoselectivity was also consequential to the formation of a C2'-acetal intermediate formed via the 2-C-acetylmethyl group and the anomeric carbonium intermediate in glycosylation.

Nanoscale Metal-Organic Frameworks That are Both Fluorescent and Hollow for Self-Indicating Drug Delivery.

Nanoscale metal-organic frameworks (MOFs) that are both fluorescent and hollow are attracting increasing interest in recent years, but ideal candidates prepared by reliable methods for biomedical applications are still very limited. Herein, we for the first time prepared tetrakis[4-(4-carboxyphenyl)phenyl]ethene (TCBPE)-based MOF nanotubes with hollow nanostructures, which could emit strong fluorescence. It was further discovered that the formation of this hollow hexagonal nanotube underwent a self-templated growth and a subsequent concaving process, which revealed that the synthesis of this MOF was kinetic rather than thermodynamic. This new MOF showed high biocompatibility, optical stability, sensitivity to pH response, and capability for exotic loading. This new MOF was further employed for efficient anti-cancer drug delivery in a self-indicating manner based on these attractive features. Therefore, this work could bring in valuable insights into the exploration of multifunctional MOFs in the field of biomedical applications by providing a new exemplar with high practical utility.