Palladium-catalyzed difluorocarbene transfer enables access to enantioenriched chiral spirooxindoles.

We disclose herein an unprecedented Pd-catalyzed difluorocarbene transfer reaction, which assembles a series of structurally interesting chiral spiro ketones with generally over 90% ee. Commercially available BrCFCOK serves as the difluorocarbene precursor, which is harnessed as a user-friendly and safe carbonyl source in this transformation. Preliminary mechanistic studies exclude the formation of free CO in the reaction process, and importantly, we also find that BrCFCOK outcompete gaseous CO and several common CO surrogates in this asymmetric process.

Photocatalytic Enantioselective Radical Cascade Multicomponent Minisci Reaction of β-Carbolines Using Diazo Compounds as Radical Precursors.

Here, a photocatalytic asymmetric multicomponent cascade Minisci reaction of β-carbolines with enamides and diazo compounds is reported, enabling an effective enantioselective radical C─H functionalization of β-carbolines with high yields and enantioselectivity (up to 83% yield and 95% ee). This enantioselective multicomponent Minisci protocol exhibits step economy, high chemo-/enantio-selective control, and good functional group tolerance, allowing access to a variety of valuable chiral β-carbolines. Notably, diazo compounds are suitable radical precursors in enantioselective cascade radical reactions.

Rh(III)-Catalyzed Diastereo- and Enantioselective Regiodivergent (Hetero)Arylamidation of (Homo)Allylic Sulfides.

A rhodium-catalyzed 3-component conjunctive diastereo- and regioselective arylamidation of (homo)allylic sulfides, organon boronic acids, and dioxazolones is reported. These reactions deliver the 1,2-insertion and 2,1-insertion arylamidation products, respectively, for allylic sulfides and homoallylic sulfides. The enantioselective arylamidation of terminal and internal allylic sulfides is achieved, furnishing various 1,3- compounds featuring one or two contiguous stereocenters in high yields and with high diastereo- and enantioselectivities.

Recent advances in Rh(I)-catalyzed enantioselective C-H functionalization.

Chiral carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds are pervasive and very essential in natural products, bioactive molecules, and functional materials, and their catalytic construction has emerged as one of the hottest research fields in synthetic organic chemistry. The last decade has witnessed vigorous progress in Rh(I)-catalyzed asymmetric C-H functionalization as a complement to Rh(II) and Rh(III) catalysis. This review aims to provide the most comprehensive and up-to-date summary covering the recent advances in Rh(I)-catalyzed C-H activation for asymmetric functionalization.

Asymmetric Hydrogenation of Racemic 2-Substituted Indoles via Dynamic Kinetic Resolution: An Easy Access to Chiral Indolines Bearing Vicinal Stereogenic Centers.

The asymmetric hydrogenation (AH) of -unprotected indoles is a straightforward, yet challenging method to access biologically interesting NH chiral indolines. This method has for years been limited to 2/3-monosubstituted or 2,3-disubstituted indoles, which produce chiral indolines bearing endocyclic chiral centers. Herein, we have reported an innovative Pd-catalyzed AH of racemic α-alkyl or aryl-substituted indole-2-acetates using an acid-assisted dynamic kinetic resolution (DKR) process, affording a range of structurally fascinating chiral indolines that contain exocyclic stereocenters with excellent yields, diastereoselectivities, and enantioselectivities.

Chiral Cp Rhodium(III)-Catalyzed Enantioselective Aziridination of Unactivated Terminal Alkenes.

Chiral cyclopentadienyl-rhodium(III) Cp Rh(III) catalysis has been demonstrated to be competent for catalyzing highly enantioselective aziridination of challenging unactivated terminal alkenes and nitrene sources. The chiral Cp Rh(III) catalysis system exhibited outstanding catalytic performance and wide functional group tolerance, yielding synthetically important and highly valuable chiral aziridines with good to excellent yields and enantioselectivities (up to 99 % yield, 93 % ee). This protocol presents a novel and effective strategy for synthesizing enantioenriched aziridines from simple alkenes.

Photocatalytic enantioselective Minisci reaction of β-carbolines and application to natural product synthesis.

A highly efficient enantioselective direct C-H functionalization of β-carbolines a Minisci-type radical process under a photo-redox and chiral phosphoric acid cooperative catalytic system has been disclosed. Through this protocol, a wide range of C1 aminoalkylated β-carbolines were constructed directly with high levels of enantioselectivities from readily available β-carbolines and alanine-derived redox-active esters. This transformation allows straightforward access to highly valuable enantioenriched β-carbolines, which are an intriguing structural motif in valuable natural products and synthetic bio-active compounds.

Enantioselective Hydroxylation of Dihydrosilanes to Si-Chiral Silanols Catalyzed by In Situ Generated Copper(II) Species.

Catalytic enantioselective hydroxylation of prochiral dihydrosilanes with water is expected to be a highly efficient way to access Si-chiral silanols, yet has remained unknown up to date. Herein, we describe a strategy for realizing this reaction: using an alkyl bromide as a single-electron transfer (SET) oxidant for invoking Cu species and chiral multidentate anionic N,N,P-ligands for effective enantiocontrol. The reaction readily provides a broad range of Si-chiral silanols with high enantioselectivity and excellent functional group compatibility.

Direct reductive amination of ketones with ammonium salt catalysed by Cp*Ir(III) complexes bearing an amidato ligand.

A series of half-sandwich Ir(III) complexes 1-6 bearing an amidato bidentate ligand were conveniently synthesized and applied to the catalytic Leuckart-Wallach reaction to produce racemic α-chiral primary amines. With 0.1 mol% of complex 1, a broad range of ketones, including aryl ketones, dialkyl ketones, cyclic ketones, α-keto acids, α-keto esters and diketones, could be transformed to their corresponding primary amines with moderate to excellent yields (40%-95%).

Mechanistic Insights into Formation of All-Carbon Quaternary Centers via Scandium-Catalyzed C-H Alkylation of Imidazoles with 1,1-Disubstituted Alkenes.

This density functional theory (DFT) study reveals a detailed plausible mechanism for the Sc-catalyzed C-H cycloaddition of imidazoles to 1,1-disubstituted alkenes to form all-carbon quaternary stereocenters. The Sc complex binds the imidazole substrate to enable deprotonative C2-H bond activation by the Sc-bound α-carbon to afford the active species. This complex undergoes intramolecular cyclization (C═C into Sc-imidazolyl insertion) with exo-selectivity, generating a β-all-carbon-substituted quaternary center in the polycyclic imidazole derivative.

Asymmetric Alkenyl C-H Functionalization by Cp Rh forms 2H-Pyrrol-2-ones through [4+1]-Annulation of Acryl Amides and Allenes.

An efficient Cp Rh -catalyzed enantioselective alkenyl C-H functionalization/[4+1] annulation of acryl amides and allenes is reported. The described transformation provides straightforward access to enantioenriched α,β-unsaturated-γ-lactams bearing a quaternary stereocenter. The reaction operates under mild conditions, displays a broad functional-group tolerance, and provides 2H-pyrrol-2-ones with excellent selectivity of up to 97:3 er.

An Enantioselective Cp Rh(III)-Catalyzed C-H Functionalization/Ring-Opening Route to Chiral Cyclopentenylamines.

A chiral Cp Rh catalyst system in situ generated from a Cp Rh (cod) precatalyst and bis(o-toluoyl) peroxide as activating oxidant was developed for a C-H activation/ring-opening sequence between aryl ketoxime ethers and 2,3-diazabicyclo[2.2.1]hept-5-enes.

Zafirlukast in combination with pseudohypericin attenuates spinal cord injury and motor function in experimental mice.

Background: Biosynthesis of leukotriene (LT) by arachidonic acid involves 5-lipoxygenase (5-LO) as an important precursor. Here, we evaluated the role of pseudohypericin (PHP) for its postulated 5-LO inhibitory activity along with a Cys-LT receptor antagonist zafirlukast (ZFL) against inflammatory response and tissue injury in mice.

Materials And Methods: The spinal injury was induced by two-level laminectomy of T6 and T7 vertebrae.

A Readily Accessible Class of Chiral Cp Ligands and their Application in Ru -Catalyzed Enantioselective Syntheses of Dihydrobenzoindoles.

Chiral cyclopentadienyl (Cp ) ligands have a large application potential in enantioselective transition-metal catalysis. However, the development of concise and practical routes to such ligands remains in its infancy. We present a convenient and efficient two-step synthesis of a novel class of chiral Cp ligands with tunable steric properties that can be readily used for complexation, giving Cp Rh , Cp Ir , and Cp Ru complexes.

microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1.

Activation of mTOR complex 1 (mTORC1) could protect human osteoblasts from dexamethasone. Tuberous sclerosis complex 1 (TSC1) is mTORC1 upstream inhibitory protein. We demonstrate here that microRNA-19a ("miR-19a", -3p) targets the 3' untranslated regions of .

Catalytic Asymmetric Dearomatization of Indolyl Dihydropyridines through an Enamine Isomerization/Spirocyclization/Transfer Hydrogenation Sequence.

A highly efficient synthesis of enantioenriched spiroindolines by catalytic asymmetric dearomatization of indolyl dihydropyridines through a chiral phosphoric acid catalyzed enamine isomerization/spirocyclization/transfer hydrogenation sequence has been developed. This reaction proceeds under mild reaction conditions, affording novel spiroindolines in good yields (up to 88 %) with excellent enantioselectivity (up to 97 % ee). DFT calculations provide insights into the reaction mechanism as well as the origin of stereochemistry.

Activation of Nrf2 by MIND4-17 protects osteoblasts from hydrogen peroxide-induced oxidative stress.

MIND4-17 is a recently developed NF-E2-related factor 2 (Nrf2) activator, which uniquely causes Nrf2 disassociation from Keap1. Here, we showed that pretreatment with MIND4-17 significantly inhibited hydrogen peroxide (HO)-induced viability reduction of primary osteoblasts and OB-6 osteoblastic cells. Meanwhile, MIND4-17 inhibited both apoptotic and non-apoptotic osteoblast cell death by HO.

MicroRNA-200a activates Nrf2 signaling to protect osteoblasts from dexamethasone.

Treatment with dexamethasone in human osteoblasts leads to oxidative stress and cell injures. NF-E2-related factor 2 (Nrf2) is a key anti-oxidant signaling. We want to induce Nrf2 activation via microRNA-mediated silencing its suppressor Keap1.

Activation of AMP-activated protein kinase by compound 991 protects osteoblasts from dexamethasone.

Dexamethasone (Dex) induces direct cytotoxicity to cultured osteoblasts. The benzimidazole derivative compound 991 ("C991") is a novel and highly-efficient AMP-activated protein kinase (AMPK) activator. Here, in both MC3T3-E1 osteoblastic cells and primary murine osteoblasts, treatment with C991 activated AMPK signaling, and significantly attenuated Dex-induced apoptotic and non-apoptotic cell death.

Albumin-Conjugated Lipid-Based Multilayered Nanoemulsion Improves Drug Specificity and Anti-Inflammatory Potential at the Spinal Cord Injury gSite after Intravenous Administration.

Albumin-conjugated multilayered nanoemulsion (albumin-MNE) of methyl prednisolone (MP) was developed to ensure the specificity of the drug at the spinal cord injury (SCI) site. MNE was prepared by emulsification followed by ionic deposition of oppositely charged polymer followed by albumin conjugation using N-hydroxysuccinimide. Prepared nanoemulsion was characterized for particle size, polydispersity index (PDI), zeta potential (Zp), pH, viscosity, and entrapment efficiency.

Phosphodiesterase inhibitor ameliorates neuronal injury in spinal cord ischemia/reperfusion injured rat model.

This study investigated the mechanisms responsible for the neuroprotective effect of sildenafil citrate (SFC) on ischemia-reperfusion spinal cord (SC) injuries. Balloon occlusion of the thoracic aorta was used to induce SC ischemia. The animals (n=30) were separated into three groups: sham, SC injury with saline, and SC injury with 5mg/kg i.

Construction of Chiral Tetrahydro-β-Carbolines: Asymmetric Pictet-Spengler Reaction of Indolyl Dihydropyridines.

A highly efficient synthesis of the enantioenriched tetrahydro-β-carbolines was developed by using a chiral phosphoric acid catalyzed Pictet-Spengler reaction of indolyl dihydropyridines. The reaction proceeds under mild reaction conditions to afford the desired chiral tetrahydro-β-carbolines in good to excellent yields (up to 96 %) and high enantioselectivities (up to 99 % ee). With this method, a formal synthesis of tangutorine and a total synthesis of deplancheine were achieved in a highly efficient manner.

Catalytic Enantioselective Transformations Involving C-H Bond Cleavage by Transition-Metal Complexes.

The development of new methods for the direct functionalization of unactivated C-H bonds is ushering in a paradigm shift in the field of retrosynthetic analysis. In particular, the catalytic enantioselective functionalization of C-H bonds represents a highly atom- and step-economic approach toward the generation of structural complexity. However, as a result of their ubiquity and low reactivity, controlling both the chemo- and stereoselectivity of such processes constitutes a significant challenge.