A5079458342- Radical Photochemical Reactions
- Catalytic C–H Functionalization Methods
- Ubiquitin and proteasome pathways
- Sulfur-Based Synthesis Techniques
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- Glycosylation and Glycoproteins Research
- Catalytic Cross-Coupling Reactions
- Asymmetric Synthesis and Catalysis
- Axial and Atropisomeric Chirality Synthesis
- Synthesis and Catalytic Reactions
- Histone Deacetylase Inhibitors Research
- X-ray Diffraction in Crystallography
- Oxidative Organic Chemistry Reactions
- Endoplasmic Reticulum Stress and Disease
Merck & Co., Inc., Rahway, NJ, USA (United States)
2020-2025
Tri-Institutional PhD Program in Chemical Biology
2019-2024
Memorial Sloan Kettering Cancer Center
2019-2024
Kettering University
2019
Shuffling nitrogen with a light push Manipulation of carbon–nitrogen rings is integral to the synthesis numerous pharmaceutical and agrochemical compounds. Jurczyk et al . report that photoexcitation carbonyl-substituted cyclic amines can shift from inside outside ring framework. The reaction appears proceed through 1,5-hydrogen electronically excited carbonyl, which sets in motion subsequent carbon–carbon bonding rearrangements. Several oxygen sulfur heterocycles were applicable as well....
Under mild blue-light irradiation, α-acylated saturated heterocycles undergo a photomediated one-atom ring contraction that extrudes heteroatom from the cyclic core. However, for nitrogenous heterocycles, this powerful skeletal edit has been limited to substrates bearing electron-withdrawing substituents on nitrogen. Moreover, mechanism and wavelength-dependent efficiency of transformation have remained unclear. In work, we increased electron richness nitrogen in azacycles improve light...
We recently reported a chiral phosphoric acid (CPA) catalyzed enantioselective photomediated ring contraction of piperidines and other saturated heterocycles. By extruding single heteroatom from ring, this transformation builds desirable C(sp3)–C(sp3) bonds in the contracted products; however, origins enantioselectivity remain poorly understood. In work, has been explored across an expanded structurally diverse substrate scope, revealing wide range enantioselectivities (0–99%) using two...
The ubiquitin (Ub) and Ub-like (Ubl) protein-conjugation cascade is initiated by E1 enzymes that catalyze Ub/Ubl activation through C-terminal adenylation, thioester bond formation with an catalytic cysteine, transfer to E2 conjugating enzymes. Each of these reactions accompanied conformational changes the domain contains cysteine (Cys domain). Open conformations Cys are associated adenylation E2s, while a closed conformation pyrophosphate release formation. Several structures available for...
Abstract Transthiolation (also known as transthioesterification) reactions are used in the biosynthesis of acetyl coenzyme A, fatty acids and polyketides, for post-translational modification by ubiquitin (Ub) ubiquitin-like (Ubl) proteins 1–3 . For Ub pathway, E1 enzymes catalyse transthiolation from an E1~Ub thioester to E2~Ub thioester. is also required transfer HECT (homologous E6AP C terminus) RBR (ring-between-ring) E3 ligases form E3~Ub thioesters 4–6 How isoenergetic bonds driven...
Ubiquitin (Ub) regulates a wide array of cellular processes through post-translational modification protein substrates. Ub is conjugated at its C-terminus to target proteins via an enzymatic cascade in which covalently bound thioesters are transferred from E1 activating enzymes E2 conjugating enzymes, and then certain E3 ligases. These transthioesterification reactions proceed transient tetrahedral intermediates. A variety chemical strategies have been used capture E1–Ub–E2 E2–Ub–E3 mimics,...
The construction of complex aza-cycles is interest to drug discovery due the prevalence nitrogen-containing heterocycles in pharmaceutical agents. Herein we report an intramolecular C-H amination approach afford value-added and complexity-enriched bridged bicyclic amines. Guided by density functional theory nuclear magnetic resonance investigations, determined unique roles light heat activation bicyclization mechanism. We applied both a synergistic fashion, achieving gram-scale aza-cycle synthesis.
A redox-relay process links two successive Pd-catalyzed cyclization reactions at remote sites to afford bicyclic ether products from readily available linear diene–diol substrates.