A5036451303- Catalytic C–H Functionalization Methods
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Ubiquitin and proteasome pathways
- Catalytic Cross-Coupling Reactions
- Radical Photochemical Reactions
- Asymmetric Hydrogenation and Catalysis
- Plant biochemistry and biosynthesis
- Chemical synthesis and alkaloids
- Sesquiterpenes and Asteraceae Studies
- 14-3-3 protein interactions
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- ATP Synthase and ATPases Research
- Glutathione Transferases and Polymorphisms
- Macrophage Migration Inhibitory Factor
- Cancer, Hypoxia, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Microbial Natural Products and Biosynthesis
- Epigenetics and DNA Methylation
- Catalytic Alkyne Reactions
- Asymmetric Synthesis and Catalysis
- Synthesis and Biological Evaluation
- Chemical Reactions and Mechanisms
- Bioactive Compounds and Antitumor Agents
Torrey Pines Institute For Molecular Studies
2023
Scripps (United States)
2023
Scripps Institution of Oceanography
2023
Scripps Research Institute
2018-2022
University of California, Berkeley
2016-2019
University of California System
2017
Berkeley College
2017
Metal-hydride hydrogen atom transfer (MHAT) functionalizes alkenes with predictable branched (Markovnikov) selectivity. The breadth of these transformations has been confined to π-radical traps; no sp3 electrophiles have reported. Here we describe a Mn/Ni dual catalytic system that hydroalkylates unactivated olefins alkyl halides, yielding aliphatic quaternary carbons.
Chemical genetic screening of small-molecule libraries has been a promising strategy for discovering unique and novel therapeutic compounds. However, identifying the targets lead molecules that arise from these screens remained major bottleneck in understanding mechanism action Here, we have coupled cysteine-reactive fragment-based covalent ligand library with an isotopic tandem orthogonal proteolysis-enabled activity-based protein profiling (isoTOP-ABPP) chemoproteomic platform to rapidly...
Chemical genetics has arisen as a powerful approach for identifying novel anti-cancer agents. However, major bottleneck of this is the targets lead compounds that arise from screens. Here, we coupled synthesis and screening fragment-based cysteine-reactive covalent ligands with activity-based protein profiling (ABPP) chemoproteomic approaches to identify impair colorectal cancer pathogenicity map druggable hotspots targeted by these hits. Through approach, discovered acrylamide DKM 3-30...
Small molecules that modulate the 14-3-3 protein-protein interaction (PPI) network represent valuable therapeutics and tool compounds. However, access has been lost to PPI molecular glues of cotylenin class, leading investigations into practical chemical syntheses congeners analogues. Here we report a concise synthesis (-)-cotylenol via 10-step asymmetric entry diversifiable 5-8-5 core. This route features mild Liebeskind-Srogl fragment coupling tolerates unprecedented steric hindrance...
Pd0 -catalyzed Mizoroki-Heck reactions traditionally exhibit poor reactivity with polysubstituted, unbiased alkenes. Intermolecular simple, all-carbon tetrasubstituted alkenes are unprecedented. Herein we report that pendant carboxylic acids, combined bulky monophospine ligands on palladium, can direct the arylation of tri- and olefins. Quaternary carbons established at high Fsp3 attached-ring junctures carboxylate directing group be removed after coupling. Carboxylate directivity prevents...
Metal-hydride hydrogen atom transfer (MHAT) functionalizes unbiased alkenes with predictable branched (Markovnikov) selectivity. The breadth of these transformations has been confined to π-radical traps; no sp<sup>3 </sup>electrophiles have reported. Here we describe a Mn/Ni dual catalytic system that allows for the hydroalkylation unactivated olefins by alkyl halides, yielding aliphatic quaternary carbons.
Abstract Pd 0 ‐catalyzed Mizoroki–Heck reactions traditionally exhibit poor reactivity with polysubstituted, unbiased alkenes. Intermolecular simple, all‐carbon tetrasubstituted alkenes are unprecedented. Herein we report that pendant carboxylic acids, combined bulky monophospine ligands on palladium, can direct the arylation of tri‐ and olefins. Quaternary carbons established at high Fsp 3 attached‐ring junctures carboxylate directing group be removed after coupling. Carboxylate directivity...
Small molecules that modulate the 14-3-3 protein-protein interaction (PPI) network represent valuable therapeutics and tool com-pounds. However, access has been lost to PPI molecular glues of cotylenin class, leading investigations into practi-cal chemical syntheses. Here we report a concise synthesis (–)-cotylenol via 10-step entry 5-8-5 binding region using convergent fragment coupling Claisen-ene cascade.
Abstract Parthenolide, a natural product from the feverfew plant and member of large family sesquiterpene lactones, exerts multiple biological therapeutic activities including anti-inflammatory anti-cancer effects. Herein, we further study parthenolide mechanism action using activity-based protein profiling (ABPP)-based chemoproteomic platforms to map additional covalent targets engaged by in human breast cancer cells. We find that parthenolide, as well other related exocyclic methylene...
Pd(0)-catalyzed, non-chain-walking Mizoroki-Heck reactions exhibit poor reactivity with polysubsti- tuted, unbiased alkenes. Intermolecular simple, all-carbon tetrasubstituted alkenes are unprecedented. Here we report that pendant carboxylic acids, combined bulky monophospine ligands on palladium, can direct the arylation of tri- and olefins. Quaternary carbons established at high Fsp3 attached-ring junctures carboxylate directing group be removed after coupling. Carboxylate directivity...
<div><div><div><p>Pd(0)-catalyzed, non-chain-walking Mizoroki-Heck reactions exhibit poor reactivity with polysubsti- tuted, unbiased alkenes. Intermolecular simple, all-carbon tetrasubstituted alkenes are unprecedented. Here we report that pendant carboxylic acids, combined bulky monophospine ligands on palladium, can direct the arylation of tri- and olefins. Quaternary carbons established at high Fsp3 attached-ring junctures carboxylate directing group be removed...
Metal-hydride hydrogen atom transfer (MHAT) functionalizes unbiased alkenes with predictable branched (Markovnikov) selectivity. The breadth of these transformations has been confined to π-radical traps; no sp 3 electrophiles have reported. Here we describe a Mn/Ni dual catalytic system that allows for the hydroalkylation unactivated olefins by alkyl halides, yielding aliphatic quaternary carbons.