Induction of neuronal differentiation in glioma cells by histone deacetylase inhibitors based on Connectivity Map discovery.

Neuron conversion leads to proliferation inhibition of glioma cells and may be an effective strategy to combat glioma and prevent recurrence. In this study, drug repositioning based on Connectivity Map (CMap) was conducted to discover drugs that could induce the differentiation of glioma cells into neuron-like cells, complemented by in vitro experimental validation. Downregulated neuronal genes in glioma were identified by the Human Protein Atlas database and the GeneCards database, and enrichment analysis and Gene Expression Profiling Interactive Analysis (GEPIA) were performed to ensure their reliability before they were uploaded to CMap for drug screening.

Cobalt/Salicylaldehyde-Enabled C-H Alkoxylation of Benzamides with Secondary Alcohols under Solvothermal Conditions.

C-O bond formation via C-H alkoxylation remains a challenge, especially coupling with a secondary alcohol, due to its low activity and sterically encumbered property. Here, we report a general and effective cobalt-catalyzed oxidative cross-coupling of benzamides with secondary alcohols via C-H alkoxylation reaction under solvothermal conditions, enabled by a salicylaldehyde/cobalt complex. The protocol features easy operation without additives, broad substrate scope, and excellent functional tolerance.

Salicylaldehyde-Cobalt(II)-Catalyzed C-H Alkoxylation of Indoles with Secondary Alcohols.

A straight and efficient protocol for the synthesis of hindered indole-ethers via C-H alkoxylation of indoles was developed by a cobalt-catalyzed cross-dehydrogenative coupling reaction with secondary alcohols. The selection of the salicylaldehyde-Co(II) catalyst enables the reaction to proceed under conditions without acid or base addition in the presence of limited alcohols. The protocol has broad substrate scope for both indole and secondary alcohols and exhibits good functional tolerance.

Selective Synthesis of Sulfonamides and Sulfenamides from Sodium Sulfinates and Amines.

An effective method was explored for the selective synthesis of sulfonamides and sulfenamides using sodium sulfinates and amines as starting materials. This method offers mild reaction conditions, a broad substrate scope, high efficiency, and readily accessible materials, making it suitable and an alternative strategy for the preparation of a variety of biologically or pharmaceutically active compounds.

Salicylaldehyde-Promoted Cobalt-Catalyzed C-H/N-H Annulation of Indolyl Amides with Alkynes: Direct Synthesis of a 5-HT3 Receptor Antagonist Analogue.

A cobalt-catalyzed annulation of the C(sp)-H/N-H bond of indoloamides with alkynes assisted by 8-aminoquinoline is reported for the synthesis of six-membered indololactams. The use of salicylaldehyde as the ligand is crucial for this transformation. The protocol has a broad scope for both alkynes and indoles.

Construction of Bulky Ligand Libraries by Ru-Catalyzed P-Assisted ortho-C-H Secondary Alkylation.

Modification of commercially available biaryl monophosphine ligands via ruthenium-catalyzed P-directed-catalyzed ortho C-H secondary alkylation is described. The use of highly ring-strained norbornene as a secondary alkylating reagent is the key to this transformation. A series of highly bulky ligands with a norbornyl group were obtained in excellent yields.

Cooperative Ligand-Promoted P-Directed Ruthenium-Catalyzed Remote -C-H Alkylation of Tertiary Phosphines.

Herein, we disclose a ruthenium-catalyzed -selective C-H activation of phosphines by using intrinsic P as a directing group. 2,2,6,6-Tetramethylheptane-3,5-dione acts as the ligand and exhibits an excellent performance in boosting the -alkylation. The protocol allows an efficient and straightforward synthesis of -alkylated tertiary phosphines.

Remote and Selective C(sp)-H Olefination for Sequential Regioselective Linkage of Phenanthrenes.

Biphenylcarboxylic acid with two competing C(sp)-H sites was designed for site selective C(sp)-H functionalization by developing carboxylic acids assisted remote and selective olefination via 7-membered palladacycle. Mechanism investigation and DFT calculations reveal a kinetics-determined process, which could be utilized to explore a variety of remote site selectivity. The practicability of this method was highlighted by the precise construction of phenathrene under sequential site selectivity.

Synthesis of seven-membered lactones by regioselective and stereoselective iodolactonization of electron-deficient olefins.

A regio- and stereoselective iodolactonization of internal electron-deficient olefinic acids has been reported, which provides a straightforward access to a series of multi-functionalized seven-membered lactones containing two consecutive chiral centers. The ester substituents on the olefins played a key role in achieving high regioselectivity. This result was proved through experiments and DFT calculations.

Late-Stage Modification of Tertiary Phosphines via Ruthenium(II)-Catalyzed C-H Alkylation.

Ru(II)-catalyzed direct alkylation of tertiary phosphines via hydroarylation of activated olefins promoted by mono--protected amino acid (MPAA) was achieved. This protocol provides a straightforward access to a large library of Buchwald-type bulky alkylated monophosphines from commercially available biaryl phosphine. Moreover, two ruthenacycle intermediates of tertiary phosphines via C-H bond cleavage were isolated to illustrate the mechanism of P(III)-directed C-H activation.

Smart pH-responsive polymeric micelles for programmed oral delivery of insulin.

The development of intelligent oral drug delivery carrier aiming at efficiently bring insulin to intestine is of great significance for diabetes mellitus therapy. In the present study, a series of amphiphilic pH-sensitive block copolymer poly(methyl methacrylate-co-methacrylicacid)-b-poly(2-amino ethyl methacrylate) [P(MMA-co-MAA)-b-PAEMA] was synthesized via activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and further self-assembled into pH-responsive cationic polymeric micelles (PCPMs) for oral insulin delivery. The structure and molecular weight were confirmed by proton nuclear magnetic resonance (H-NMR), Fourier transforming infrared spectrum (FT-IR) and gel permeation chromatography (GPC), respectively.

Switchable Synthesis of Arylalkynes and Phthalides via Controllable Palladium-Catalyzed Alkynylation and Alkynylation-Annulation of Benzoic Acids with Bromoalkynes.

A ligand-promoted palladium(II)-catalyzed synthesis of arylalkynes and phthalides from benzoic acids and bromoalkynes via carboxylate-assisted ortho-C-H activation is reported. A series of phthalides with various functional groups are prepared via ortho-alkynylation and alkynylation-annulation. Moreover, the key ortho-alkynylated products are also obtained by controlling the reaction conditions.

Ruthenium-Catalyzed Gram-Scale Preferential C-H Arylation of Tertiary Phosphine.

A general protocol for site-preferential mono-C-H arylation of tertiary phosphine ligands catalyzed by a ruthenium(II) complex was devised. This protocol gives access to a series of modified Buchwald-biaryl monophosphines on a gram scale in moderate to excellent yields. A catalytic cycle is proposed derived from knowledge of the intermediates observed by ESI-MS.

Carboxylate-Assisted Pd(II)-Catalyzed ortho-C-H and Remote C-H Activation: Economical Synthesis of Pyrano[4,3- b]Indol-1(5 H)-ones.

An original Pd(II)-catalyzed domino two C-H activations strategy has been designed to synthesize pyrano[4,3- b]indol-1(5 H)-one motifs from inexpensive and commercially available olefins and heteroaromatic acids by carboxylate-directed sequential ortho-C-H alkenylation and remote C-H lactonization. Importantly, this protocol overcomes the selectivity for carboxylic acids with acrylates of the conventional Michael addition-type process. Preliminary studies of mechanism indicate that both aryl and olefinlic C-H activations may participate in this catalytic system.

Facile synthesis of unnatural β-germyl-α-amino amides via Pd(ii)-catalyzed primary and secondary C(sp)-H bond germylation.

Pd(ii)-Catalyzed direct C(sp3)-H germylation of α-AA derivatives with the assistance of a bidentate auxiliary for the efficient synthesis of β-germyl-α-amino amides is reported. This protocol features good generality for primary and secondary C-H bonds of aliphatic amides. Mechanistic studies show that a crucial five-membered palladacycle intermediate may play a key role in this process.

Monoprotected Amino Acid (MPAA) Ligand Enabled C-H Alkynylation of Phenyl Acetic Acid.

A weakly carboxylate-directed palladium(II)-catalyzed ortho-C-H alkynylation of diverse phenylacetic acids promoted by monoprotected amino acid ligand enabled is reported. The reaction has a broad substrate scope including α-secondary, tertiary, and quaternary phenylacetic acids. Notably, the direct ortho-C-H alkynylation of α-quaternary phenylacetic acids and chiral α-tertiary phenylacetic acids was achieved for the first time.

Tracking the Progress and Mechanism Study of a Solvothermal in Situ Domino N-Alkylation Reaction of Triethylamine and Ammonia Assisted by Ferrous Sulfate.

Atom economic in situ domino N-alkylation reactions of triethylamine/ammonia with 2-(hydroxymethyl)quinolin-8-ol (HL-OH) assisted by FeSO·7HO were realized under mild solvothermal conditions at 120 °C in acetonitrile. The resulting tripodal 2,2',2″-[nitrilotris(methylene)]tris(quinolin-8-ol) (HL-N) forms a linear trimer [Fe(L-N)] (1). Electrospray ionization mass spectrometry of the reaction solution provides evidence for the intermediates of three steps, while crystallography and X-ray photoelectron spectroscopy characterize the trimer.

Application of mesoscale simulation to explore the aggregate morphology of pH-sensitive nanoparticles used as the oral drug delivery carriers under different conditions.

The pH-sensitive nanoparticles are selected as the potentially promising oral protein and peptide drug carriers due to their excellent performance. With the poly (lactic-co-glycolic acid)/hydroxypropyl methylcellulose phthalate (PLGA/HP55) nanoparticle as a model nanoparticle, the structure-property relationship of nanoparticles with different conditions is investigated by dissipative particle dynamics (DPD) simulations in our work. In the oral drug delivery system, the poly (lactic-co-glycolic acid) (PLGA) is hydrophobic polymer, hydroxypropyl methylcellulose phthalate (HP55) is pH-sensitive enteric polymer which used to protect the nanoparticles through the stomach and polyvinyl alcohol (PVA) is hydrophilic polymer as the stabilizer.

Divergent and Stereoselective Synthesis of β-Silyl-α-Amino Acids through Palladium-Catalyzed Intermolecular Silylation of Unactivated Primary and Secondary C-H Bonds.

A general and practical Pd -catalyzed intermolecular silylation of primary and secondary C-H bonds of α-amino acids and simple aliphatic acids is reported. This method provides divergent and stereoselective access to a variety of optical pure β-silyl-α-amino acids, which are useful for genetic technologies and proteomics. It can also be readily performed on a gram scale and the auxiliary can be easily removed with retention of configuration.

Pd-Catalyzed α-Selective C-H Functionalization of Olefins: En Route to 4-Imino-β-Lactams.

Pd-catalyzed α-olefinic C-H activation of simple α,β-unsaturated olefins has been developed. 4-imino-β-lactam derivatives were readily synthesized via activation of α-olefinic C-H bonds with excellent cis stereoselectivity. A wide range of heterocycles at the β-position are compatible with this reaction.

Mesoscopic simulation studies on the formation mechanism of drug loaded polymeric micelles.

In this work, the formation of polymeric micelles as drug delivery vehicles in an aqueous environment is investigated by dissipative particle dynamics (DPD) simulations. Doxorubicin (DOX) is selected as the model drug, whereas docosahexaenoic acid (DHA) conjugated His10Lys10 (DHA-His10Lys10) as the drug carrier. It is shown from DPD simulation that drug molecules and DHA-His10Lys10 molecules could aggregate and form micelles under a defined composition recipe; drug molecules are homogeneously distributed inside the carrier matrix, on whose surface the stabilizer lysine segments are absorbed.

Copper-/Silver-Mediated Arylation of C(sp(2))-H Bonds with 2-Thiophenecarboxylic Acids.

A copper/silver-mediated arylation of (hetero)aryl C-H bonds with 2-thiophenecarboxylic acids has been achieved. The protocol features a broad substrate scope and high functional group tolerance. Preliminary mechanistic studies indicate that a cascade protodecarboxylation/dehydrogenative coupling process is likely involved.

Ni(II)-catalyzed dehydrative alkynylation of unactivated (hetero)aryl C-H bonds using oxygen: a user-friendly approach.

Ni(II)-catalyzed dehydrative alkynylation of unactivated C(sp(2))-H bonds with terminal alkynes under atmospheric pressure of oxygen was developped. This reaction features the use of catalytic amounts of nickel as the catalyst and O2 as the sole oxidant, providing a user-friendly approach to the synthesis of aryl alkynes.

Ni(II)/BINOL-catalyzed alkenylation of unactivated C(sp(3))-H bonds.

The first nickel-catalyzed alkenylation of unactivated C(sp(3))-H bonds with vinyl iodides is described. The catalytic system comprises an inexpensive and air-stable Ni(acac)2 as the catalyst and BINOL as the ligand, which is highly efficient for the alkenylation of β-methyl C(sp(3))-H bonds of a broad range of aliphatic carboxamides. The resulting olefins can serve as versatile handles for further preparation.