Glycosyl Radical-Based Synthesis of -Alkyl Glycosides Bearing a Cyclopropane via a Deoxygenative Giese Addition-Reduction-Cyclization Cascade.

We have developed a glycosyl radical-based synthesis of -alkyl glycosides through a deoxygenative Giese addition-reduction-cyclization cascade, in which readily available 1-hydroxy carbohydrates serve as precursors for glycosyl radicals and aryl alkenes function as radical acceptors. This reaction not only provides an effective method for accessing a previously underexplored class of functionalized cyclopropanes but also enhances the application of Giese addition in the synthesis of -alkyl glycosides by derivatizing the radical intermediate generated through polar cyclization to yield a cyclopropane.

Radical Deoxygenative Three-Component Reaction of Alcohols, Aryl Alkenes, and Cyanopyridines.

We report herein a deoxygenative radical multicomponent reaction involving alcohols, aryl alkenes, and cyanopyridine under photoredox conditions. This method is photoredox-neutral, suitable for late-stage modification, and compatible with a wide array of alcohols as alkyl radical sources, including primary, secondary, and tertiary alcohols. This reaction comprises a radical relay mechanism encompassing the Giese addition of aryl alkenes by alkyl radicals, followed by the decyanative pyridination of benzyl radicals.

Synthesis and Biological Activities of Scleropentaside D.

We report the first total synthesis of scleropentaside D, a unique -glycosidic ellagitannin, from the ketal derivative of scleropentaside A employing site-selective O4-protection of -acyl glycoside and copper-catalyzed oxidative coupling reaction of galloyl groups as the key steps. Our study confirms the proposed structure of this natural product, scleropentaside D, and demonstrates its effectiveness as an inhibitor of α-glycosidase.

Bioinspired Mechanochromic Liquid Crystal Materials: From Fundamentals to Functionalities and Applications.

Inspired by intriguing color changeable ability of natural animals, the design and fabrication of artificial mechanochromic materials capable of changing colors upon stretching or pressing have attracted intense scientific interest. Liquid crystal (LC) is a self-organized soft matter with anisotropic molecular alignment. Due to the sensitivity to various external stimulations, LC has been considered as an emerging and appealing responsive building block to construct intelligent materials and advanced devices.

Dehydroxylative radical N-glycosylation of heterocycles with 1-hydroxycarbohydrates enabled by copper metallaphotoredox catalysis.

N-Glycosylated heterocycles play important roles in biological systems and drug development. The synthesis of these compounds heavily relies on ionic N-glycosylation, which is usually constrained by factors such as labile glycosyl donors, precious metal catalysts, and stringent conditions. Herein, we report a dehydroxylative radical method for synthesizing N-glycosides by leveraging copper metallaphotoredox catalysis, in which stable and readily available 1-hydroxy carbohydrates are activated for direct N-glycosylation.

Quaternization-spiro design of chlorine-resistant and high-permeance lithium separation membranes.

Current polyamide lithium extraction nanofiltration membranes are susceptible to chlorine degradation and/or low permeance, two problems that are hard to reconcile. Here we simultaneously circumvented these problems by designing a quaternized-spiro piperazine monomer and translating its beneficial properties into large-area membranes (1 × 2 m) via interfacial polymerization with trimesoyl chloride. The quaternary ammonium and spiral conformation of the monomer confer more positive charge and free volume to the membrane, leading to one of the highest permeance (~22 L m h bar) compared to the state-of-the-art Mg/Li nanofiltration membranes.

Metallaphotoredox-Enabled Construction of the P(O)-N Bond from Aromatic Amines and P(O)-H Compounds.

We have developed a dual copper/photoredox-catalyzed approach for the construction of the P(O)-N bond from commercially available aromatic amines and P(O)-H compounds. This metallaphotoredox method avoids toxic or corrosive reagents and does not require prefunctionalized substrates. The reaction has a broad substrate scope and is suitable for the synthesis of phosphonamides and phosphinamides, thus complementing the previous nonphotochemical approaches.

Preparation of glycosyl carboxylic acids stereoselective synthesis and oxidative cleavage of -vinyl glycosides.

We have developed an improved cyanide-free strategy for the synthesis of glycosyl carboxylic acids, employing stereoselective -vinyl glycosylation and oxidative cleavage of -vinyl glycosides as key steps. Compared to our previous work, the amount of NaIO required for the oxidative cleavage step is reduced significantly from 18 equivalents to 4.5 equivalents.

De Novo Synthesis of Orthogonally-Protected C2-Fluoro Digitoxoses and Cymaroses: Development and Application for the Synthesis of Fluorinated Digoxin.

Inspired by Roush's pioneering work on rare sugars, we have developed a scalable, stereoselective, de novo synthesis of orthogonally protected C2-fluoro digitoxose and cymarose, utilizing Sharpless kinetic resolution and organocatalytic fluorination as key steps. The utility of this strategy is demonstrated by the synthesis of a fluorinated analogue of digoxin, which indicates the fluorine on the sugar ring may have a significant impact on biological activity.

Glycosyl-Radical-Based Synthesis of -Alkyl Glycosides via Photomediated Defluorinative -Difluoroallylation.

We have developed a stereoselective, glycosyl radical-based method for the synthesis of -alkyl glycosides via a photomediated defluorinative -difluoroallylation reaction. We demonstrate for the first time that glycosyl radicals, generated from glycosyl bromides, can readily participate in a photomediated radical polar crossover process, affording a diverse array of -difluoroalkene containing -glycosides. Notable features of this method include scalability, mild conditions, broad substrate scope, and suitability for the late-stage modification of complex molecules.

1,2--Stereoselective Synthesis of -Glycosides of 2-Deoxy-2-amino-sugars Involving Glycosyl Radicals.

We report for the first time that the imidate radical can be efficiently added to glycals to generate glycosyl radicals, based on which a general, toxic-reagent-free synthesis of -glycosides of 2-deoxy-2-amino sugars has been developed. Complementary to previous strategies, the reaction is 1,2--stereoselective and could use aryl alkenes as substrates. The late-stage functionalization and density functional theory calculations are reported.

Copper-Catalyzed Reductive Ring-Cleavage of Isoxazoles: Synthesis of Fluoroalkylated Enaminones and Application for the Preparation of Celecoxib, Deracoxib, and Mavacoxib.

We have identified a new reactivity of copper/diamine catalysis for the reductive ring-cleavage of isoxazoles to yield fluoroalkylated enaminones. This protocol has the advantage of using commercially available reagents, ease of setting up, broad tolerance of functionality, and is regiospecific and free of defluorination and reduction of reducible functional groups. The utility was demonstrated by a one-step, regioselective synthesis of fluoroalkylated pyrazole-based drugs such as celecoxib, deracoxib, and mavacoxib.

Oxidize Amines to Nitrile Oxides: One Type of Amine Oxidation and Its Application to Directly Construct Isoxazoles and Isoxazolines.

A facile oxidative heterocyclization of commercially available amines and -butyl nitrite with alkynes or alkenes leading to isoxazoles or isoxazolines is described. The unprecedented strategy of the oxidation of an amine directly to a nitrile oxide was used in this cyclization process. This reaction is highly efficient, regiospecific, operationally simple, mild, and tolerant of a variety of functional groups.

Cyanide-Free Synthesis of Glycosyl Carboxylic Acids and Application for the Synthesis of Scleropentaside A.

We have developed a cyanide-free strategy for the synthesis of glycosyl carboxylic acids, which can provide 1,2- or 1,2- glycosyl carboxylic acids and is compatible with common protecting groups. The synthetic utility was demonstrated by the synthesis of 12 unreported glycosyl acids and the total synthesis of scleropentaside A.

Diastereoselective synthesis and conformational analysis of 4,5-difluoropipecolic acids.

Stereoselectively-fluorinated analogs of pipecolic acid have been investigated through a combined theoretical and experimental approach. Three of the four possible diastereoisomers of 4,5-difluoropipecolic acid were successfully synthesized via deoxyfluorination chemistry, navigating a complex reaction network that included neighboring group participation, rearrangement, and elimination pathways. A DFT-based conformational study, supported by NMR J-based analysis, revealed that the different diastereoisomers of 4,5-difluoropipecolic acid preferentially adopt different puckers of the six-membered ring.

A β-glucan from Grifola frondosa effectively delivers therapeutic oligonucleotide into cells via dectin-1 receptor and attenuates TNFα gene expression.

Grifola frondosa is an edible and medicinal mushroom with great nutritional values and bioactivities. In the present study, a soluble homogeneous β-glucan, GFPS, with high molecular mass of 5.42 × 10 Da was purified from the fruit bodies of Grifola frondosa using 5% cold NaOH.

Synthesis of tri(di)fluoroethylanilines via copper-catalyzed coupling reaction of tri(di)fluoroethylamine with (hetero)aromatic bromides.

We have realized the first Ullmann type coupling reaction of tri(di)fluoroethylamine with (hetero)aromatic bromides, employing 5-20 mol% CuO and an oxalamide ligand [N-(2,4,6-trimethoxyphenyl)acetamide]. This efficient and practical method has the following features: (i) avoids the use of an expensive catalyst; (ii) does not require anhydrous solvent and strict air extrusion; (iii) uses bench stable and inexpensive (hetero)aromatic bromides; (iv) is suitable for the synthesis of fluoroalkylated hetero-aromatic substrates; (v) is suitable for gram-scale synthesis. This work also shows the "negative fluorine effect" for the alkylamines in the copper catalysed coupling reactions.

Hydroximoyl fluorides as the precursors of nitrile oxides: synthesis, stability and [3 + 2]-cycloaddition with alkynes.

The transformation of hydroximoyl fluorides to nitrile oxides for [3 + 2]-cycloaddition with alkynes has been achieved for the first time. The hydroximoyl fluorides used in this work appeared to be not stable, which was proved by a series of experiments. A DFT calculation was performed to better understand the properties of hydroximoyl fluorides.

Cu-Catalyzed/mediated synthesis of N-fluoroalkylanilines from arylboronic acids: fluorine effect on the reactivity of fluoroalkylamines.

An oxidative coupling reaction of fluoroalkylamines with arylboronic acids has been achieved for the first time. Fluorine has profound influence on the reactivity and fluoroalkylated amines have the following reactivity trend: difluoroethylamine > trifluoroethylamine > pentafluoropropylamine ≈ heptafluorobutylamine.

Cu-Catalyzed Synthesis of Fluoroalkylated Isoxazoles from Commercially Available Amines and Alkynes.

A one-pot protocol for the construction of fluoroalkylated isoxazoles directly from commercially available amines and alkynes is described. The reaction is scalable, operationally simple, regioselective, mild, and tolerant of a broad range of functional groups. As such, it could be viewed as a "click synthesis" of fluoroalkylated isoxazoles.

Esterification of Carboxylic Acids with Difluoromethyl Diazomethane and Interrupted Esterification with Trifluoromethyl Diazomethane: A Fluorine Effect.

It is demonstrated that difluoromethyl diazomethane (HCFCHN) can react with a broad range of carboxylic acids. The reaction is convenient, operationally simple, mild, and tolerant of a variety of different functional groups. In sharp contrast, trifluoromethyl diazomethane (CFCHN) fails to react with carboxylic acids in most solvents, and in acetonitrile this reagent instead undergoes an interrupted esterification (a Mumm reaction) to yield N-trifluoroethyl imides.