Rhodium(III)-Catalyzed Intermolecular Direct Amidation of Aldehyde C–H Bonds with <i>N</i>‑Chloroamines at Room Temperature

A Rh(III)-catalyzed direct aldehyde C–H amidation from aldehydes and N-chloroamines, prepared in situ from amines, has been developed via C–H bond activation under very mild reaction conditions. A variety of primary and secondary amines were used to afford the corresponding amides in moderate to excellent yields

Rhodium(III)-Catalyzed Intermolecular Direct Amidation of Aldehyde C–H Bonds with <i>N</i>‑Chloroamines at Room Temperature

A Rh(III)-catalyzed direct aldehyde C–H amidation from aldehydes and <i>N</i>-chloroamines, prepared in situ from amines, has been developed via C–H bond activation under very mild reaction conditions. A variety of primary and secondary amines were used to afford the corresponding amides in moderate to excellent yields

Rhodium-Catalyzed Direct Addition of Aryl C–H Bonds to Nitrosobenzenes at Room Temperature

An unprecedented Rh-catalyzed direct addition of aryl C–H bonds to nitrosobenzenes has been developed under very mild reaction conditions (room temperature). The reaction is highly step-, atom-, and redox-economic and compatible with air and water to <i>N</i>-selectively provide a variety of <i>N</i>-diarylhydroxylamines in good to excellent yields. More importantly, this process may provide a new direction for C–N bond formation through direct C(sp²)–H functionalization

Rh(III)-Catalyzed C–H Amidation with <i>N</i>‑Hydroxycarbamates: A New Entry to <i>N</i>‑Carbamate-Protected Arylamines

An unprecedented Rh­(III)-catalyzed direct intermolecular C–H amidation with <i>N</i>-hydroxycarbamates has been developed. Different directing groups, such as pyridine, pyrimidine, pyrazole, and <i>N</i>-OMe oxime, can be employed in this C–H amidation process, providing valuable <i>N</i>-carbamate-protected arylamines (e.g., Cbz, Moz, Ac, Boc, and Fmoc). More importantly, this process may afford a new avenue for intermolecular C–H amidation where readily available <i>N</i>-hydroxycarbamates can be used as the nitrogen sourc

A graphic model for MMAE enhanced cGAMP-mediated antiviral immunity.

MMAE changed cGAMP-mediated STING trafficking routes from ER to Golgi apparatus by disrupting the microtubule network, and delayed the trafficking-mediated STING degradation. MMAE dispersed the cGAMP-mediated STING perinuclear puncta into large number of tiny vesicles throughout the cytoplasm. The accumulated STING vesicles further amplified the cGAMP-mediated TBK1-STING-IRF3 signaling cascade, and promoted the production of IFNs and ISGs expression. MMAE alone restricted viral replication and infection by destroying microtubule networks, while MMAE combined with cGAMP exerted potent and broad-spectrum antiviral activity in vitro and in vivo in a STING-dependent manner.</p

Rh(III)-Catalyzed C–H Amidation with <i>N</i>‑Hydroxycarbamates: A New Entry to <i>N</i>‑Carbamate-Protected Arylamines

An unprecedented Rh­(III)-catalyzed direct intermolecular C–H amidation with <i>N</i>-hydroxycarbamates has been developed. Different directing groups, such as pyridine, pyrimidine, pyrazole, and <i>N</i>-OMe oxime, can be employed in this C–H amidation process, providing valuable <i>N</i>-carbamate-protected arylamines (e.g., Cbz, Moz, Ac, Boc, and Fmoc). More importantly, this process may afford a new avenue for intermolecular C–H amidation where readily available <i>N</i>-hydroxycarbamates can be used as the nitrogen sourc

MMAE relied on the host STING pathway to enhance cGAMP antiviral immune response.

(A-H and I-P) WT and Stinggt/gt C57BL/6 mice (n = 10) were treated with PBS, cGAMP (30 μg/mice), MMAE (0.5 mg/kg), or cGAMP along with MMAE by intraperitoneal injection (i.p.) for 2 h. Then, the mice were infected intravenously with HSV-1-GFP at 2 × 108 pfu per WT mouse or at 1 × 107 pfu per Stinggt/gt mouse. (A and I) Survival curves of virus-infected mice after treatments were analyzed using the log-rank (Mantel-Cox) test. (B, C and J, K) Body weight and body condition score of mice were observed and recorded daily. Body condition score was measured and calculated as in previous research with minor modifications [52] (normal = 0). (D-H and L-P) Six days after virus infection, three C57BL/6 mice (WT and Stinggt/gt) were randomly selected for subsequent experiments. (D and L) The viral titers in mouse brains were measured by qRT-PCR assay (n = 3 biological replicates). (E, F, M, and N) Expressions of viral genes in brains were measured by immunoblotting and qPCR analysis (n = 3). (G and O) Expressions of IFNβ and ISGs in brains were analyzed by qPCR analysis (n = 3). (H and P) IFNβ production in brains were qualified by ELISA assay.</p

MMAE enhanced cGAMP-mediated antiviral activity <i>in vitro</i>.

(A-C and E) THP1 cells (WT, STING KO) and L929 cells (WT, STING KO) were infected with VSV-GFP (MOI = 0.1) and HSV-1-GFP (MOI = 1) respectively, and then cultured cGAMP (0.5 μM) and/or MMAE (0.25 μM) for 24 h. The cells were imaged with Olympus IX83 Inverted fluorescence microscope. The fluorescence intensity of viral GFP was determined by ImageJ software, shown on the right of each row of images (n = 15, biological replicates). Scale bars, 100 μm. (D) STING protein were analyzed by immunoblotting in L929 cells (WT and STING KO). (F) L929 cells (STING KO) were infected with HSV-1-GFP (MOI = 1), and then cultured cGAMP (0.5 μM) or MMAE (0.25 μM) for indicated times. Viral propagation was determined by western blot. The results are representative of three independent biological replicates. Bars are the mean ± SEM. Significance was determined by one-way ANOVA; *p p p p (TIF)</p

MMAE changed STING trafficking routes and promoted cGAMP-mediated STING activity.

(A-C and F) HeLa cells stably expressing human STING-GFP were stimulated with cGAMP (8 μM) and/or MMAE (1 μM), or VcMMAE (1 μM) for 2 h. (A and F) Live cells were stained by ER-Tracker Blue-White DPX and LysoTracker Deep Red. (B and C) Cells were fixed, permeabilized, and stained for GM130 (a Golgi protein, red) or tubulin (red). Nuclei were stained with DAPI (blue). All structured illumination microscope (3D-SIM) images are z-stack images. Scale bars, 10 μm. 3D-SIM images was acquired and processed using the Highly Intelligent and Sensitive SIM (HIS-SIM), and Wiener deconvolution was used in reconstructed images. Dashed white boxes in each main image indicate enlarged areas of interest shown below. Co-localization was quantified using Pearson’s correlation coefficient (r), shown on the right of each row of images (n = 50). (D and E) BJ-5ta cells were stimulated with cGAMP (8 μM) with or without MMAE (pre-treatment for 30 min), bafilomycin A1 (BafA1, 100 nM), or brefeldin A (BFA, 1 μM) for 2 h. Total STING protein was quantified by image J software (n = 3 biological replicates). (G and H) STING stability was analyzed by immunoblotting in the absence or presence of cycloheximide (CHX, 50 μg/ml). BJ-5ta cells were treated and analyzed as in (D and E).</p

Rh(III)-Catalyzed Intramolecular Redox-Neutral or Oxidative Cyclization of Alkynes: Short, Efficient Synthesis of 3,4-Fused Indole Skeletons

A Rh­(III)-catalyzed intramolecular redox-neutral or oxidative annulation of a tethered alkyne has been developed to efficiently construct 3,4-fused indoles via a C–H activation pathway. The advantages of this process are (1) ready availability of annulation precursors; (2) broad substrate scope; (3) complete regioselectivity; (4) simple and mild reaction conditions; and (5) no need for an external oxidant or to employ molecular oxygen as the stoichiometric terminal oxidant