t-BuOLi promoted regioselective N-thiolation of indoles with N-arylthio phthalimide.

The selective N-thiolation of indole substrates poses a challenge due to their diminished nucleophilicity at nitrogen. Herein, we present a novel method for the thiolation of the NH group in indole derivatives by using N-arylthio phthalimide as the sulfur source, t-BuOLi as the base and MeCN as the solvent. The process was successfully conducted under transition metal catalyst-free and room temperature conditions with a high product yield and a short reaction time. The developed protocol exhibited excellent regioselectivity and broad substrate tolerance in the preparation of N-thioindoles with diverse functional groups.

TfOH-Catalyzed Cascade Reaction: Metal-Free Access to 3,3-Disubstituted Phthalides from o-Alkynylbenzoic Acids.

A facile new method for the synthesis of 3,3-disubstituted phthalides is reported. A successive reaction process begins with the TfOH-catalyzed cyclization of o-alkynylbenzoic acids followed by an ortho-regioselective electrophilic alkylation of various electron-rich aromatic compounds or alkenes, which has been successfully developed. The corresponding regioselective products of 3-substituted phthalide were obtained in good to high yields.

Solvent-switchable regioselective 1,2- or 1,6-addition of quinones with boronic acids.

An efficient copper-catalyzed solvent-switchable regioselective 1,2- or 1,6-addition of quinones with boronic acids has been developed. This novel catalytic protocol for the synthesis of various quinols and 4-phenoxyphenols was enabled by a simple solvent swap between H2O and MeOH. It features mild reaction conditions, simple and easy operation, broad substrate scope and excellent regioselectivity. The gram-scale reactions as well as the further transformations of both addition products were also successfully investigated.

Advance and Designing Strategies in Polymeric Antifungal Agents Inspired by Membrane-Active Peptides.

The high-mortality invasive fungal infections seriously threaten the lives of immunocompromised people. Host defense peptides and cell-penetrating peptides are representative membrane-active peptides with different functions. Among them, host defense peptides mimicking is a valid strategy in the design of synthetic antifungal agents. Despite the brilliance in the field of intracellular delivery, the potential of cell-penetrating peptides and their mimics for designing antifungal agents has been overlooked. In this concept article, we describe the structural design of synthetic antifungal polymers as mimics of host defense peptides, and highlight the effectiveness and potential of cell-penetrating peptide-inspired strategy in designing potent and selective antifungal polymeric agents. In addition, an outlook for further expanding the design horizons of antifungal polymers is also presented.

An Effective Strategy to Develop Potent and Selective Antifungal Agents from Cell Penetrating Peptides in Tackling Drug-Resistant Invasive Fungal Infections.

The high mortality rate of invasive fungal infections and quick emergence of drug-resistant fungal pathogens urgently call for potent antifungal agents. Inspired by the cell penetrating peptide (CPP) octaarginine (R8), we elongated to 28 residues poly(d,l-homoarginine) to obtain potent toxicity against both fungi and mammalian cells. Further incorporation of glutamic acid residues shields positive charge density and introduces partial zwitterions in the obtained optimal peptide polymer that displays potent antifungal activity against drug-resistant fungi superior to antifungal drugs, excellent stability upon heating and UV exposure, negligible in vitro and in vivo toxicity, and strong therapeutic effects in treating invasive fungal infections. Moreover, the peptide polymer is insusceptible to antifungal resistance owing to the unique CPP-related antifungal mechanism of fungal membrane penetration followed by disruption of organelles within fungal cells. All these merits imply the effectiveness of our strategy to develop promising antifungal agents.

[Development of a first-class undergraduate major in bioengineering facing the emerging engineering direction of biomedicine].

In the "Tutorial for outline of the healthy China 2030 plan", biomedicine was listed as a key planning and development area. Shanghai government also lists biomedicine as an emerging pillar industry. The rapid development of biomedicine industry put higher requirement for talents. Taking the idea of cross integration, mutually beneficial development, inheritance and innovation, the School of Biotechnology of East China University of Science and Technology organically integrates bioengineering and pharmaceutical majors to develop a new undergraduate engineering program of biomedicine, which specially reforms the talent training practice from the aspects of developing a "trinity teaching" standard system, a "three integration, three convergence" curriculum system, and a "three comprehensive education" innovative talent training system. We put forward the trinity of "value guidance, knowledge system, technology and non-technical core competence literacy" to foster emerging biomedicine engineering talents, and developed a comprehensive innovative talents training mode featured by "covering class-in and class-out, covering every student, and covering ideology and curriculum". Moreover, we established effective connections between courses and training goals, between general education courses and professional courses, and between top-notch talent training systems and training programs. Based on the achievements of teaching reform of the emerging engineering program "intelligent bio-manufacturing", the experience we obtained may provide ideas for development of the first-class bioengineering major in China.

Copper-Catalyzed Three-Component Reactions of α-Ketoaldehyde, 1,3-Dicarbonyl Compound, and Organic Boronic Acid in Water: A Route to 1,4-Diketones.

A novel three-component reaction of α-ketoaldehydes, 1,3-dicarbonyl compounds, and organic boronic acids catalyzed by CuO in water has been developed to give a wide range of products containing 1,3/1,4-diketones. The method has some advantages such as the use of readily available starting materials, wide substrate scopes, excellent yields, gram-scale synthesis, and mild reaction conditions.

Tunable Synthesis of α-Amino Boronic Esters from Available Aldehydes and Amines through Sequential One-Pot Dehydration and Copper-Catalyzed Borylacylation.

Copper-catalyzed multicomponent borylacylation of imines with acid chlorides and bis(pinacolato)diboron was developed for the preparation of synthetically useful and pharmacologically relevant α-amino boronic acid derivatives. Starting from a range of acid chlorides and imines with aryl, heteroaryl, and alkyl substituents, most of these ligand-free reactions proceeded smoothly at room temperature in moderate to good yields. Furthermore, a facile and convenient one-pot, multistep access to the direct synthesis of α-amino boronic acid derivatives from available aldehydes and amines was also developed.

Catalyst-free chemoselective α-sulfenylation/ß-thiolation for α,ß-unsaturated carbonyl compounds.

A novel, efficient, catalyst-free and product-controllable strategy has been developed for the chemoselective α-sulfenylation/ß-thiolation of α,ß-unsaturated carbonyl compounds. An aromatic sulfur group could be chemoselectively introduced at α- or ß-position of carbonyls with different sulfur reagents under slightly changed reaction conditions. A series of desired products were obtained in moderate to excellent yields. Mechanistic studies revealed that B2pin2 played the key role in activating the transformation towards the ß-thiolation of α,ß-unsaturated carbonyl compounds. This transition-metal-catalyst-free method provides a convenient and efficient tool for the highly chemoselective preparation of α-thiolation or ß-sulfenylation products of α,ß-unsaturated carbonyl compounds.

Copper-catalyzed alkylarylation of activated alkenes using isocyanides as the alkyl source: an efficient radical access to 3,3-dialkylated oxindoles.

A novel and efficient protocol for the synthesis of 3,3-dialkylated oxindoles is described. The method involves a copper-catalyzed tandem radical addition/cyclization of N-arylacrylamides with the alkyl radicals generated from isocyanides. Two C-C bonds are formed in a single step.

Microwave-Assisted Copper-Catalyzed Oxidative Cyclization of Acrylamides with Non-Activated Ketones.

An operationally simple and efficient microwave-assisted protocol for the oxidative cyclization of acrylamide derivatives with non-activated ketones to generate 3,3-disubstituted oxindoles is described. The reaction proceeds by a copper-catalyzed tandem radical addition/cyclization strategy and tolerates a series of functional groups with moderate to excellent yields.

Pd-catalyzed Csp(2) -H functionalization of heteroarenes via isocyanide insertion: concise synthesis of di-(hetero)aryl ketones and di-(hetero)aryl alkylamines.

We report herein an efficient Pd-catalyzed direct C-H bond functionalization of heteroarenes via an isocyanide insertion strategy for the synthesis of di-(hetero)aryl ketones and di-(hetero)aryl alkylamines. The methodology involves a three component reaction between an azole, a haloarene and an isocyanide resulting in the formation of an imine, which in turn is either hydrolyzed or reduced to get the desired product.

Lyotropic liquid crystal phases of phytantriol in a protic ionic liquid with fluorous anion.

The phase behaviour of phytantriol in the protic ionic liquid (PIL) 1-methylimidazolium pentadecafluorooctanoate (MImOF) and four different MImOF-water compositions was investigated by small- and wide-angle X-ray scattering (SAXS/WAXS), cross polarised optical microscopy (CPOM) and infrared spectroscopy (IR). MImOF is a distinct protic ionic liquid in that it contains a fluorocarbon anion and a hydrocarbon cation. This leads to MImOF having an unusual liquid nanostructure, such that it contains fluorocarbon, hydrocarbon and polar domains. No lyotropic liquid crystal phases were observed for phytantriol in neat MImOF. However, on addition of water, lamellar, cubic Ia3¯d and micellar phases were observed for specific MImOF-phytantriol-water compositions at room temperature, and up to 60 °C. The phase behaviour for phytantriol in the solvent mixture of 25 wt%-MImOF-75 wt%-water was the most similar to the phytantriol-water phase diagram. Only this MImOF-water composition supported the Ia3¯d cubic phase, which had a lattice parameter between 100-140 Å compared to 86-100 Å in deionised water, indicating significant swelling due to the MImOF. IR spectroscopy showed that a percentage of the water molecules were hydrogen bonded to the N-H of the MIm cation, and this water decreased the hydrogen bonding present between the cation and anion of the ionic liquid. This investigation furthers our understanding of the interaction of ionic liquids with solutes, and the important role that the different IL nanostructures can have on influencing these interactions.

Synthesis of tertiary propargylamines via a rationally designed multicomponent reaction of primary amines, formaldehyde, arylboronic acids and alkynes.

A novel approach for the synthesis of tertiary propargylamines is achieved through a Cu(OAc)2-catalyzed multicomponent reaction of primary amines, formaldehyde, arylboronic acids and alkynes, where a combination of PBM and A(3)-coupling reactions is involved in this new multicomponent reaction.

A simple and efficient synthesis of fused morpholine pyrrolidines/piperdines with potential insecticidal activities.

A simple and efficient synthesis of fused morpholine pyrrolidine/piperdine core structures was accomplished via a Petasis-borono Mannich reaction of cyclic amino alcohols, glyoxal and arylboronic acids with moderate to good yields. The bioassay data showed that the synthesized compounds displayed selective insecticidal activities against armyworm and root-knot nematode.

Direct olefination of benzaldehydes into 1,3-diarylpropenes via a copper-catalyzed heterodomino Knoevenagel-decarboxylation-Csp(3)-H activation sequence.

Copper-catalyzed direct olefination of benzaldehydes into 1,3-diarylpropenes by a novel domino Knoevenagel-decarboxylation-Csp(3)-H activation sequence is reported. This method provides a concise and effective route toward the synthesis of unsymmetrical 1,3-diarylpropene derivatives.

Ionic liquid-supported synthesis of piperazine derivatives as potential insecticides.

With the purpose of extending our efforts on the search and synthesis of new insecticides with novel acting modes, a series of novel 4-(2-(4-(pyridin-2-yl)piperazin-1-yl)ethoxy)aniline derivatives were designed based on classical serotonin receptor ligands and synthesized through the rapid ionic liquid-supported parallel synthesis with yields up to 88 %. These products were purified through the convenient washing with appropriate solvents and isolated in good yield. In addition, 27 amide or urea derivatives of anilines were also prepared. Bioassay data showed that some of the synthesized compounds displayed selective insecticidal bioactivities against tested pests.

Sequential [3 + 2] and [4 + 2] cycloadditions for stereoselective synthesis of a novel polyheterocyclic scaffold.

A strategy of combining [3 + 2] cycloaddition and intramolecular Diels-Alder reaction is developed for the synthesis of a novel polycyclic scaffold with skeletal and substitutional diversities. Intermediates generated from stereoselective [3 + 2] cycloaddition of azomethine ylides and maleimides were derivatized for intramolecular Diels-Alder reaction of furan to form highly condensed heterocyclic products as racemic single diastereomers.

Fluorous protic ionic liquids exhibit discrete segregated nano-scale solvent domains and form new populations of nano-scale objects upon primary alcohol addition.

Fluorous protic ionic liquids (FPILS) containing a perfluorinated anion and hydrocarbon cation have been observed to segregate into nano-scale fluorocarbon, hydrocarbon and polar domains. The solubility and interactions of ethanol and butanol in a series of FPILs has been investigated by synchrotron source small and wide angle X-ray scattering. Nano-scale objects were found to be present within the binary solutions from low concentrations of FPILs in alcohols to around 40 to 80 wt% FPIL. The FPILs retain their fluorocarbon, hydrocarbon and polar domains in binary mixtures with alcohols in addition to the formation of nano-scale alcohol associated objects. For comparison, the influence of alcohols on the nano-scale segregation of analogous protic ionic liquids (PILs) which contained hydrocarbon anions in place of the perfluorinated anions was also investigated. The ethanol and butanol were miscible with the PILs across the full concentration range, with no evidence for the formation of analogous nano-scale objects. The FPILs are prospective solvents which may enable simultaneous solubility of fluorocarbon, hydrocarbon and polar species.

Protic ionic liquids with fluorous anions: physicochemical properties and self-assembly nanostructure.

A series of 11 new protic ionic liquids with fluorous anions (FPILs) have been identified and their self-assembled nanostructure, thermal phase transitions and physicochemical properties were investigated. To the best of our knowledge this is the first time that fluorocarbon domains have been reported in PILs. The FPILs were prepared from a range of hydrocarbon alkyl and heterocyclic amine cations in combination with the perfluorinated anions heptafluorobutyrate and pentadecafluorooctanoate. The nanostructure of the FPILs was established by using small- and wide-angle X-ray scattering (SAXS and WAXS). In the liquid state many of the FPILs showed an intermediate range order, or self-assembled nanostructure, resulting from segregation of the polar and nonpolar hydrocarbon and fluorocarbon domains of the ionic liquid. In addition, the physicochemical properties of the FPILs were determined including the melting point (T(m)), glass transition (T(g)), devitrification temperature (T(c)), thermal stability and the density ρ, viscosity η, air/liquid surface tension γ(LV), refractive index n(D), and ionic conductivity κ. The FPILs were mostly solids at room temperature, however two examples 2-pyrrolidinonium heptafluorobutyrate (PyrroBF) and pyrrolidinium heptafluorobutyrate (PyrrBF) were liquids at room temperature and all of the FPILs melted below 80 °C. Four of the FPILs exhibited a glass transition. The two liquids at room temperature, PyrroBF and PyrrBF, had a similar density, surface tension and refractive index but their viscosity and ionic conductivity were very different due to dissimilar self-assembled nanostructure.