Correction to Catalytic Enantioselective Desymmetrization of 1,3-Diazido-2-propanol via Intramolecular Interception of Alkyl Azides with Diazo(aryl)acetates

Correction to Catalytic Enantioselective Desymmetrization of 1,3-Diazido-2-propanol via Intramolecular Interception of Alkyl Azides with Diazo(aryl)acetate

Catalytic Enantioselective Desymmetrization of 1,3-Diazido-2-propanol via Intramolecular Interception of Alkyl Azides with Diazo(aryl)acetates

The first catalytic enantioselective desymmetrization of 1,3-diazido-2-propanol via an intramolecular interception of alkyl azides by Cu–carbenoids has been realized. A wide range of 1,3-diazidoisopropyl diazo­(aryl)­acetates were converted to cyclic α-imino esters in the presence of bisoxazoline ligand (<i>S,S</i>)-Ph-Box with good to excellent yields, and the enantiomeric excess was up to 97%

Catalytic Enantioselective Desymmetrization of 1,3-Diazido-2-propanol via Intramolecular Interception of Alkyl Azides with Diazo(aryl)acetates

The first catalytic enantioselective desymmetrization of 1,3-diazido-2-propanol via an intramolecular interception of alkyl azides by Cu–carbenoids has been realized. A wide range of 1,3-diazidoisopropyl diazo­(aryl)­acetates were converted to cyclic α-imino esters in the presence of bisoxazoline ligand (<i>S,S</i>)-Ph-Box with good to excellent yields, and the enantiomeric excess was up to 97%

Catalytic Enantioselective Desymmetrization of 1,3-Diazido-2-propanol via Intramolecular Interception of Alkyl Azides with Diazo(aryl)acetates

The first catalytic enantioselective desymmetrization of 1,3-diazido-2-propanol via an intramolecular interception of alkyl azides by Cu–carbenoids has been realized. A wide range of 1,3-diazidoisopropyl diazo­(aryl)­acetates were converted to cyclic α-imino esters in the presence of bisoxazoline ligand (<i>S,S</i>)-Ph-Box with good to excellent yields, and the enantiomeric excess was up to 97%

Formation of <i>S</i>‑[2‑(<i>N</i>⁶‑Deoxyadenosinyl)ethyl]glutathione in DNA and Replication Past the Adduct by Translesion DNA Polymerases

1,2-Dibromoethane (DBE, ethylene dibromide) is a potent carcinogen due at least in part to its DNA cross-linking effects. DBE cross-links glutathione (GSH) to DNA, notably to sites on 2′-deoxyadenosine and 2′-deoxyguanosine (Cmarik, J. L., et al. (1991) J. Biol. Chem. 267, 6672−6679). Adduction at the N6 position of 2′-deoxyadenosine (dA) had not been detected, but this is a site for the linkage of <i>O</i>⁶-alkylguanine DNA alkyltransferase (Chowdhury, G., et al. (2013) Angew. Chem. Int. Ed. 52, 12879−12882). We identified and quantified a new adduct, <i>S</i>-[2-(<i>N</i>⁶-deoxyadenosinyl)­ethyl]­GSH, in calf thymus DNA using LC-MS/MS. Replication studies were performed in duplex oligonucleotides containing this adduct with human DNA polymerases (hPols) η, ι, and κ, as well as with <i>Sulfolobus solfataricus</i> Dpo4, <i>Escherichia coli</i> polymerase I Klenow fragment, and bacteriophage T7 polymerase. hPols η and ι, Dpo4, and Klenow fragment were able to bypass the adduct with only slight impedance; hPol η and ι showed increased misincorporation opposite the adduct compared to that of unmodified 2′-deoxyadenosine. LC-MS/MS analysis of full-length primer extension products by hPol η confirmed the incorporation of dC opposite <i>S</i>-[2-(<i>N</i>⁶-deoxyadenosinyl)­ethyl]­GSH and also showed the production of a −1 frameshift. These results reveal the significance of <i>N</i>⁶-dA GSH-DBE adducts in blocking replication, as well as producing mutations, by human translesion synthesis DNA polymerases

La tierra : bosquejos de la vida rural

A designed Tf₂O-promoted intramolecular Schmidt reaction of 2-substituted ω-azido carboxylic acids was demonstrated. Tf₂O was used as an activation reagent for the carboxylic acid, and ω-azido anhydride was in situ generated, releasing a molecular TfOH, which acted as an acid promoter for the Schmidt process. A series of 2-substituted pyrrolidines was produced and acetylated for better purification. The strategy was also efficient for conversion of a 4-substituted ω-azido carboxylic acid to the tricyclic lactam

Iridium(III)-Based PD-L1 Agonist Regulates p62 and ATF3 for Enhanced Cancer Immunotherapy

Anti-PD-L1 immunotherapy, a new lung cancer treatment, is limited to a few patients due to low PD-L1 expression and tumor immunosuppression. To address these challenges, the upregulation of PD-L1 has the potential to elevate the response rate and efficiency of anti-PD-L1 and alleviate the immunosuppression of the tumor microenvironment. Herein, we developed a novel usnic acid-derived Iridium(III) complex, Ir-UA, that boosts PD-L1 expression and converts “cold tumors” to “hot”. Subsequently, we administered Ir-UA combined with anti-PD-L1 in mice, which effectively inhibited tumor growth and promoted CD4+ and CD8+ T cell infiltration. To our knowledge, Ir-UA is the first iridium-based complex to stimulate the expression of PD-L1 by explicitly regulating its transcription factors, which not only provides a promising platform for immune checkpoint blockade but, more importantly, provides an effective treatment strategy for patients with low PD-L1 expression

Iridium(III)-Based PD-L1 Agonist Regulates p62 and ATF3 for Enhanced Cancer Immunotherapy

Anti-PD-L1 immunotherapy, a new lung cancer treatment, is limited to a few patients due to low PD-L1 expression and tumor immunosuppression. To address these challenges, the upregulation of PD-L1 has the potential to elevate the response rate and efficiency of anti-PD-L1 and alleviate the immunosuppression of the tumor microenvironment. Herein, we developed a novel usnic acid-derived Iridium(III) complex, Ir-UA, that boosts PD-L1 expression and converts “cold tumors” to “hot”. Subsequently, we administered Ir-UA combined with anti-PD-L1 in mice, which effectively inhibited tumor growth and promoted CD4+ and CD8+ T cell infiltration. To our knowledge, Ir-UA is the first iridium-based complex to stimulate the expression of PD-L1 by explicitly regulating its transcription factors, which not only provides a promising platform for immune checkpoint blockade but, more importantly, provides an effective treatment strategy for patients with low PD-L1 expression

Preparation of Optically Active <i>cis</i>-Cyclopropane Carboxylates: Cyclopropanation of α‑Silyl Stryenes with Aryldiazoacetates and Desilylation of the Resulting Silyl Cyclopropanes

Optically active <i>cis</i>-cyclopropane carboxylates are prepared via the Rh₂(<i>S</i>-PTAD)₄-catalyzed cyclopropanation of α-silyl styrenes with aryl diazoacetates followed by desilylation of the resulting silyl cyclopropane carboxylates. The conjugation of the aryl ring with CC bond and π stacking are proposed for the stereoselectivity of cyclopropanation, and configuration inversion is observed with the desilylation process

Mass Spectrometric Identification of Water-Soluble Gold Nanocluster Fractions from Sequential Size-Selective Precipitation

This paper presents a simple and convenient methodology to separate and characterize water-soluble gold nanocluster stabilized with penicillamine ligands (AuNC-SR) in aqueous medium by sequential size-selective precipitation (SSSP) and mass spectrometry (MS). The highly polydisperse crude AuNC-SR product with an average core diameter of 2.1 nm was initially synthesized by a one-phase solution method. AuNCs were then precipitated and separated successively from larger to smaller ones by progressively increasing the concentration of acetone in the aqueous AuNCs solution. The SSSP fractions were analyzed by UV–vis spectroscopy, matrix-assisted laser desorption/ionization time-of-flight-MS, and thermogravimetric analysis (TGA). The MS and TGA data confirmed that the fractions precipitated from 36, 54, 72, and 90% v/v acetone (<i>F</i>_36%, <i>F</i>_54%, <i>F</i>_72%, and <i>F</i>_90%) comprised families of close core size AuNCs with average molecular formulas of Au₃₈(SR)₁₈, Au₂₈(SR)₁₅, Au₁₈(SR)₁₂, and Au₁₁(SR)₈, respectively. In addition, <i>F</i>_36%, <i>F</i>_54%, <i>F</i>_72%, and <i>F</i>_90% contained also the typical magic-sized gold nanoparticles of Au₃₈, Au₂₅, Au₁₈, and Au₁₁, respectively, together with some other AuNCs. This study shed light on the potential use of SSSP for simple and large-scale preliminary separation of polydisperse water-soluble AuNCs into different fractions with a relatively narrower size distribution