Comprehending the inhibition mechanism of indole-based bis-acylhydrazone compounds on α-glucosidase: Spectral and theoretical approaches.

Indole-based bis-acylhydrazone compounds can inhibit the activity of α-glucosidase and control the concentration of blood glucose. In this paper, the characteristics of three indole-based bis-acylhydrazone compounds with different inhibitory activities of α-glucosidase as well as the interaction with α-glucosidase were studied by experiments and computational simulation techniques. Enzyme kinetic and spectral experiments showed that the indole-based bis-acylhydrazone compounds were able to inhibit enzyme activity through mixed inhibition dominated by competitive inhibition, and during the binding reaction, indole-based bis-acylhydrazone compounds can quench the intrinsic fluorescence of α-glucosidase through static quenching and an aggregation of the indole-based bis-acylhydrazone with α-glucosidase produces a stable complex with a molar ratio of 1:1, and the combination of indole-based bis-acylhydrazone compounds could lead to slight change in the conformation of α-glucosidase.

Pd-Catalyzed Atroposelective C-H Olefination: Diverse Synthesis of Axially Chiral Biaryl-2-carboxylic Acids.

Axially chiral carboxylic acids are important motifs in chiral catalysts and ligands. We herein reported the synthesis of axially chiral carboxylic acids via Pd(II)-catalyzed atroposelective C-H olefination using carboxylic acid as the native directing group. A broad range of axial chiral biaryl-2-carboxylic acids were synthesized in good yields with high enantioselectivities (up to 84% yield with 99% ee).

Au-Catalyzed Asymmetric Polyene Cyclization and Its Application in the Total Synthesis of (+)-2-Ketoferruginol, (+)-Fleuryinol B, (+)-Salviol, and (-)-Erythroxylisin A.

A catalytic asymmetric 1,3-acyloxy shift/polyene cyclization cascade has been achieved with good enantioselectivities under the catalysis of the chiral Au(I) reagent. The synthetic utility of this method has been showcased by the catalytic asymmetric total syntheses of (+)-2-ketoferruginol, (+)-fleuryinol B, and (+)-salviol. Notably, the first enantioselective total synthesis of (-)-erythroxylisin A has also been realized in 15 steps.

Palladium Catalyzed Annulation of -Iodo-Anilines with Propargyl Alcohols: Synthesis of Substituted Quinolines.

A palladium catalyzed annulation of -iodo-anilines with propargyl alcohols for the synthesis of substituted quinolines has been developed. The reaction tolerates diverse functional groups under mild conditions, providing direct access to 2,4-disubstituted quinolines from easily available starting materials. A broad range of 2,4-disubstituted quinolines were efficiently prepared in good to excellent yields.

Bicyclic Amidine-Triggered Cyclization of -Alkynylisocyanobenzenes: Synthesis of Lactam-Derived Quinolines.

Efficient access to the synthesis of lactam-derived quinoline through a bicyclic amidine-triggered cyclization reaction from readily prepared -alkynylisocyanobenzenes has been developed. The reaction was initiated by nucleophilic attack of the bicyclic amidines to -alkynylisocyanobenzenes, subsequently with intramolecular cyclization to produce a DBU-quinoline-based amidinium salt, followed by hydrolysis to afford the lactam-derived quinoline in moderate to good yields.

Rh(I)-Catalyzed [5 + 2]/[2 + 2] Cycloaddition Cascade to Access a Cyclobutane-Fused [4-5-6-7] Tetracyclic Framework.

A Rh(I)-catalyzed [5 + 2]/[2 + 2] cycloaddition cascade has been developed to afford a complex and highly strained [4-5-6-7] tetracyclic framework in good yields and excellent diastereoselectivities. During this transformation, three rings, three C-C bonds, and four contiguous stereocenters were formed efficiently. Mechanistically, the rare sterically congested multisubstituted cyclobutanes are constructed readily through Michael addition and a Mannich reaction cascade.

Catalyst-Controlled Nickel-Catalyzed Intramolecular -Selective C-H Cyclization of Benzimidazoles with Alkenes.

Compared with the widely explored -selective C-H cyclization, transition metal-catalyzed -selective C-H cyclization of benzimidazoles with alkenes has been a formidable challenge. Previous efforts mainly rely on substrate-controlled methods, rendering the product complexity restricted. Herein we report a catalyst-controlled method to facilitate -cyclization, in which a bulky -heterocyclic carbene ligand and BuOK base-enabled Ni-Al bimetallic catalyst prove critical to the selectivity.

InI-catalyzed polyene cyclization of allenes and its application in the total synthesis of seven abietane-type diterpenoids.

A novel polyene cyclization using the allene group as the initiator has been successfully developed. This methodology provides an efficient strategy for the construction of an abietane-type tricyclic skeleton with a functionalizable C2-C3 double bond and features a wide substrate scope and excellent stereoselectivities. Potential utility of this approach has been well demonstrated by the collective total synthesis of seven abietane-type diterpenoids.

Alteration of gut microbiota in high-fat diet-induced obese mice using carnosic acid from rosemary.

(rosemary) is widely used as a food ingredient. Rosemary extract (containing 40% carnosic acid) exhibited potent antiobesity activity. However, the relationship between carnosic acid (CA) and changes in the gut microbiota of high-fat diet (HFD)-induced obese mice has not been fully investigated.

Synthesis and bioactivities evaluation of oleanolic acid oxime ester derivatives as -glucosidase and -amylase inhibitors.

Different oleanolic acid (OA) oxime ester derivatives (-) were designed and synthesised to develop inhibitors against -glucosidase and -amylase. All the synthesised OA derivatives were evaluated against -glucosidase and -amylase Among them, compound showed the highest -glucosidase inhibition with an IC of 0.35 µM, which was ∼1900 times stronger than that of acarbose, meanwhile compound exhibited the highest -amylase inhibitory with an IC of 3.

Pd(II)-Catalyzed Atroposelective C-H Allylation: Synthesis of Enantioenriched -Aryl Peptoid Atropisomers.

A Pd-catalyzed atroposelective C-H allylation with 1,1-disubstituted alkenes was developed for the synthesis of enantioenriched -aryl peptoid atropisomers via β-H elimination using commercially available and inexpensive L-Glu-OH as a chiral ligand. Exclusive allylic selectivity was achieved. Additionally, a series of enantioenriched -aryl peptoid atropisomers were obtained in synthetically useful yields with excellent enantioselectivities (up to 90% yield and 97% ee).

Divergent Synthesis of Skeletally Distinct Arboridinine and Arborisidine.

A divergent synthesis of skeletally distinct arboridinine and arborisidine was achieved. The central divergent strategy was inspired by the divergent biosynthetic cyclization mode of arboridinine and arborisidine and their hidden topological connection. The branch point was reached through a Michael and Mannich cascade process.

Copper-catalyzed monoselective C-H amination of ferrocenes with alkylamines.

A copper-catalyzed mono-selective C-H amination of ferrocenes assisted by 8-aminoquinoline is presented here. A range of amines, including bioactive molecules, were successfully installed to the -position of ferrocene amides with high efficiency under mild conditions. A range of functionalized ferrocenes were compatible to give the aminated products in moderate to good yields.

Synthesis of Chiral Sulfoxides via Pd(II)-Catalyzed Enantioselective C-H Alkynylation/Kinetic Resolution of 2-(Arylsulfinyl)pyridines.

A Pd(II)-catalyzed enantioselective C-H alkynylation of 2-(arylsulfinyl)pyridines via kinetic resolution using cheap and commercially available l-Glu-OH as a chiral ligand is reported. A wide range of 2-(arylsulfinyl)pyridines were compatible with this protocol, giving the alkynylation products and recovered sulfoxides in high yields with high enantioselectivities (up to 99% ee). Furthermore, the enantioenriched products can be easily transformed to several other types of chiral sulfoxide scaffolds with the retention of enantiopurity.

TEMPO-Enabled Electrochemical Enantioselective Oxidative Coupling of Secondary Acyclic Amines with Ketones.

An electrochemical asymmetric coupling of secondary acyclic amines with ketones via a Shono-type oxidation has been described, affording the corresponding amino acid derivatives with good to excellent diastereoselectivity and enantioselectivity. The addition of an -oxyl radical as a redox mediator could selectively oxidize the substrate rather than the product, although their oxidation potential difference is subtle (about 13 mV). This electrochemical transformation proceeds in the absence of stoichiometric additives, including metals, oxidants, and electrolytes, which gives it good functional group compatibility.

and studies of bis (indol-3-yl) methane derivatives as potential α-glucosidase and α-amylase inhibitors.

In this paper, bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated for their inhibitory activity against α-glucosidase and α-amylase. All synthesised compounds showed potential α-glucosidase and α-amylase inhibitory activities. Compounds (IC: 7.

Novel cinnamic acid magnolol derivatives as potent α-glucosidase and α-amylase inhibitors: Synthesis, in vitro and in silico studies.

In this study, twenty novel cinnamic acid magnolol derivatives were synthesized, and screened for their anti-hyperglycemic potential. All synthesized compounds exhibited good to moderate α-glucosidase and α-amylase inhibitory activities with IC values: 5.11 ± 1.

Pd(II)-Catalyzed enantioselective arylation of unbiased methylene C(sp)-H bonds enabled by a 3,3'-F-BINOL ligand.

Palladium-catalyzed asymmetric functionalization of unbiased methylene C(sp3)-H bonds is a long-standing challenge. Here, we report a Pd(ii)-catalyzed highly enantioselective arylation of unbiased methylene C(sp3)-H bonds enabled by a strongly coordinating bidentate 2-pyridinylisopropyl (PIP) directing group and an easily accessible 3,3'-F2-BINOL chiral ligand. The use of aryl iodides with the combination of 3,3'-F2-BINOL was beneficial for high enantiocontrol.

Brønsted Acid-Catalyzed Formal (3+3)-Annulation of Propargylic (Aza)--Quinone Methides with 4-Hydroxycoumarins and 1,3-Dicarbonyl Compounds.

Herein, we describe a highly effective 1,8-conjugate-addition-mediated formal (3+3)-annulation of (aza)--quinone methides generated from propargylic alcohols with 4-hydroxycoumarins and 1,3-dicarbonyl compounds under the catalysis of a Brønsted acid. This methodology affords efficient and practical access to synthetically important and highly functionalized pyranocoumarins and pyrans in excellent yields under mild conditions. Importantly, these products exhibit impressive inhibitory activity toward α-glucosidase.

Effects of atorvastatin in combination with celecoxib and tipifarnib on proliferation and apoptosis in pancreatic cancer sphere-forming cells.

Cancer stem cell (CSC) plays an important role in pancreatic cancer pathogenesis and treatment failure. CSCs are characterized by their ability to form tumor spheres in serum-free medium and expression of CSC related markers. In the present study, we investigated the effect atorvastatin, celecoxib and tipifarnib in combination on proliferation and apoptosis in Panc-1 sphere-forming cells.

Asymmetric Total Synthesis and Assignment of Absolute Configuration of Arbornamine.

The asymmetric total synthesis of arbornamine was accomplished in 13 steps, leading to the assignment of its absolute configuration. The key features of the strategy include construction of the C16 quaternary carbon center by a highly diastereoselective Grignard reagent addition to --butanesulfinylimine, sequential site-selective amidation and -alkylation to form the C and E rings, and [Ni(COD)]-mediated Michael addition to close the D ring.

Synthesis of Naphthopyrans via Formal (3+3)-Annulation of Propargylic (Aza)--Quinone Methides with Naphthols.

Herein, we report an efficient Brønsted acid-catalyzed formal (3+3)-annulation of (aza)--quinone methides generated in situ from propargylic alcohols with naphthol derivatives, which involves a 1,8-conjugate addition/6-endo annulation process. This protocol provides an effective method for preparing important functionalized pyranocoumarins under mild conditions.

Synergistic anti-inflammatory effects of silibinin and thymol combination on LPS-induced RAW264.7 cells by inhibition of NF-κB and MAPK activation.

Background: Combination drug therapy has become an effective strategy for inflammation control. The anti‑inflammatory capacities of silibinin and thymol have each been investigated on its own, but little is known about the synergistic anti-inflammatory effects of these two compounds.

Purpose: This study aims to investigate the synergistic anti-inflammatory effects of silibinin and thymol when administered in combination to lipopolysaccharide (LPS)-induced RAW264.