A5046292368- Catalytic C–H Functionalization Methods
- Cyclopropane Reaction Mechanisms
- Hemoglobinopathies and Related Disorders
- Epigenetics and DNA Methylation
- Catalytic Alkyne Reactions
- Oxidative Organic Chemistry Reactions
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Asymmetric Hydrogenation and Catalysis
- Chromatin Remodeling and Cancer
- Synthetic Organic Chemistry Methods
- Asymmetric Synthesis and Catalysis
- Chronic Kidney Disease and Diabetes
- Pharmacological Effects and Toxicity Studies
- RNA modifications and cancer
- Cancer-related gene regulation
- Catalytic Cross-Coupling Reactions
- DNA and Nucleic Acid Chemistry
- Cyclization and Aryne Chemistry
- Synthesis and Biological Activity
- Synthesis and Reactions of Organic Compounds
- Parathyroid Disorders and Treatments
Novartis (United States)
2021-2024
The University of Texas at Austin
2012-2014
Sickle cell disease (SCD) is a prevalent, life-threatening condition attributable to heritable mutation in β-hemoglobin. Therapeutic induction of fetal hemoglobin (HbF) can ameliorate complications and has been intently pursued. However, safe effective small-molecule inducers HbF remain elusive. We report the discovery dWIZ-1 dWIZ-2, molecular glue degraders WIZ transcription factor that robustly induce erythroblasts. Phenotypic screening cereblon (CRBN)-biased chemical library revealed as...
Here we report the first highly enantioselective Rh-catalyzed carboacylation of olefins via C–C bond activation benzocyclobutenones. Good yields and excellent enantioselectivities (92–99% ee, 14 examples) were obtained for substrates with various steric electronic properties. In addition, fully saturated poly-fused rings prepared from products through a challenging catalytic reductive dearomatization approach. These investigations provide distinct way to prepare chiral carbon frameworks that...
Abstract The rhodium‐catalyzed formation of all‐carbon spirocenters involves a decarbonylative coupling trisubstituted cyclic olefins and benzocyclobutenones through CC activation. metal–ligand combination [{Rh(CO) 2 Cl} ]/P(C 6 F 5 ) 3 catalyzed this transformation most efficiently. A range diverse spirocycles were synthesized in good to excellent yields many sensitive functional groups tolerated. mechanistic study supports hydrogen‐transfer process that occurs β‐H...
Abstract The rhodium‐catalyzed formation of all‐carbon spirocenters involves a decarbonylative coupling trisubstituted cyclic olefins and benzocyclobutenones through CC activation. metal–ligand combination [{Rh(CO) 2 Cl} ]/P(C 6 F 5 ) 3 catalyzed this transformation most efficiently. A range diverse spirocycles were synthesized in good to excellent yields many sensitive functional groups tolerated. mechanistic study supports hydrogen‐transfer process that occurs β‐H...
Bromodomain-containing proteins frequently reside in multisubunit chromatin complexes with tissue or cell state-specific compositions. Recent studies have revealed tumor-specific dependencies on the BAF complex bromodomain subunit BRD9 that are a result of recurrent mutations afflicting structure and composition associated members. To enable study ligand engaged assemblies, we established chemoproteomics approach using functionalized derivative BI-9564 as an affinity matrix. Unexpectedly,...
Sickle cell disease (SCD) is a prevalent, life-threatening condition with few treatment options, attributed to heritable mutation in β-hemoglobin. Therapeutic induction of fetal hemoglobin (HbF) small molecules has been pursued as ameliorate many complications but limited success. Herein, we report the discovery 10, novel, potent, and selective molecular glue degrader transcription factor WIZ that robustly induces HbF expression potential for SCD. 10 was optimized from phenotypic screening...
Abstract A range of diverse spirocycles are synthesized in good to excellent yields and many sensitive functional groups tolerated.
Abstract A modified access to the benzocyclobutene motif via [2 + 2] cycloaddition between benzynes generated from dehydrohalogenation of aryl halides and acetaldehyde enolate in situ THF is presented.
Abstract This method can be used to prepare certain nontrivial chiral carbon frameworks.
Abstract Bromodomain-containing proteins frequently reside in multisubunit chromatin complexes with tissue or cell state-specific compositions. Recent studies have revealed tumor-specific dependencies on the BAF complex bromodomain subunit BRD9 that are a result of recurrent mutations afflicting structure and composition associated members. To enable study ligand engaged assemblies, we established chemoproteomics approach using functionalized derivative BI-9564 as an affinity matrix....