A5053777262- Radical Photochemical Reactions
- Synthesis and Catalytic Reactions
- Catalytic C–H Functionalization Methods
- Protein Tyrosine Phosphatases
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Galectins and Cancer Biology
- Atherosclerosis and Cardiovascular Diseases
- RNA modifications and cancer
- Fluorine in Organic Chemistry
- Oxidative Organic Chemistry Reactions
- Sulfur-Based Synthesis Techniques
- Electrochemical Analysis and Applications
- Asymmetric Synthesis and Catalysis
- Crystallography and molecular interactions
- Advanced Photocatalysis Techniques
- Synthesis and Biological Activity
- Pharmacological Effects of Natural Compounds
- Nanoplatforms for cancer theranostics
- Bioactive Compounds and Antitumor Agents
- Peptidase Inhibition and Analysis
- Immune cells in cancer
- Veterinary medicine and infectious diseases
- Chemical synthesis and alkaloids
AbbVie (United States)
2021-2023
University of Wisconsin–Madison
2012-2019
California Institute of Technology
2018
Abstract Irradiation of vinyl and aryl azides with visible light in the presence Ru photocatalysts results formation reactive nitrenes, which can undergo a variety CN bond‐forming reactions. The ability to use low‐energy instead UV photochemical activation avoids competitive photodecomposition processes that have long been significant limitation on synthetic these
Abstract Immune checkpoint blockade is effective for some patients with cancer, but most are refractory to current immunotherapies and new approaches needed overcome resistance 1,2 . The protein tyrosine phosphatases PTPN2 PTPN1 central regulators of inflammation, their genetic deletion in either tumour cells or immune promotes anti-tumour immunity 3–6 However, challenging drug targets; particular, the active site has been considered undruggable. Here we present discovery characterization...
α,β-Unsaturated 2-imidazolyl ketones undergo [2 + 2] cycloaddition with a variety of Michael acceptors upon irradiation visible light in the presence Ru(bpy)(3)(2+). Cleavage imidazolyl auxiliary from cycloadducts affords cyclobutane carboxamides, esters, thioesters, and acids that would not be accessible direct corresponding unsaturated carbonyl compounds.
Abstract Azidoformates are interesting potential nitrene precursors, but their direct photochemical activation can result in competitive formation of aziridination and allylic amination products. Herein, we show that visible‐light‐activated transition‐metal complexes be triplet sensitizers selectively produce aziridines through the spin‐selective photogeneration nitrenes from azidoformates. This approach enables a wide range alkenes formal oxyamination enol ethers using alkene as limiting...
Over the past decade, there has been a renewed interest in use of transition metal polypyridyl complexes as photoredox catalysts for variety innovative synthetic applications. Many derivatives these are known, and effect ligand modifications on their efficacy subject extensive, systematic investigation. However, influence photocatalyst counteranion received little attention, despite fact that generally cationic nature. Herein, we demonstrate effects exert surprising, dramatic impact rate...
An 18-step synthesis of the antibiotic (+)-pleuromutilin is disclosed. The key steps include a highly stereoselective SmI2-mediated cyclization to establish eight-membered ring and stereospecific transannular [1,5]-hydrogen atom transfer set C10 stereocenter. This strategy was also used prepare (+)-12-epi-pleuromutilin. chemistry described here will enable efforts new mutilin antibiotics.
Abstract Irradiation of vinyl and aryl azides with visible light in the presence Ru photocatalysts results formation reactive nitrenes, which can undergo a variety CN bond‐forming reactions. The ability to use low‐energy instead UV photochemical activation avoids competitive photodecomposition processes that have long been significant limitation on synthetic these
Abstract Azidoformates are interesting potential nitrene precursors, but their direct photochemical activation can result in competitive formation of aziridination and allylic amination products. Herein, we show that visible‐light‐activated transition‐metal complexes be triplet sensitizers selectively produce aziridines through the spin‐selective photogeneration nitrenes from azidoformates. This approach enables a wide range alkenes formal oxyamination enol ethers using alkene as limiting...
Abstract Immune checkpoint blockade is effective for a subset of patients across many cancers, but most are refractory to current immunotherapies and new approaches needed overcome resistance. The protein tyrosine phosphatase PTPN2 central regulator inflammation, genetic deletion on either tumor cells or host immune promotes anti-tumor immunity. However, inhibitors have not been described. Here, we present the validation ABBV-CLS-484, potent catalytic inhibitor closely related PTPN1....
Abstract Background: Pharmacologic inhibition of PTPN2 and PTPN1 (PTPN2/N1) represents a novel therapeutic approach in immuno-oncology that augments innate adaptive immune responses addition to enhancing tumor cell sensitivity immune-mediated killing. PTPN2/N1 emerged as top hits an vivo CRISPR screen identify tumor-intrinsic targets enhance overcome resistance anti-PD-1 treatment. are phosphatases act negative regulators numerous pathways including activation. While have long been interest,...
We report operationally facile methods for the synthesis of substituted dihydroisoquinolinones and tetrahydroisoquinolines from readily accessible o-bromobenzyl bromides o-bromobenzaldehydes, respectively. While classical electrophilic aromatic substitution reactions are tailored to construction saturated isoquinolines derived electron-rich precursors, we demonstrate efficient syntheses electronically diverse substrates produce cyclized products as single regioisomers.
Abstract The use of this strategy enables the synthesis a variety cyclobutane carboxylic acid derivatives which are not accessible from direct cycloaddition corresponding unsaturated carbonyl compounds.
Abstract Immune checkpoint blockade is effective for a subset of patients across many cancers, but most are refractory to current immunotherapies and new approaches needed overcome resistance. The protein tyrosine phosphatase PTPN2 central regulator inflammation, genetic deletion on either tumour cells or host immune promotes anti-tumour immunity. However, inhibitors with suitable pharmacokinetic properties oral administration have not been described. Here, we present the characterization...