A5031428200- Chemical synthesis and alkaloids
- Microbial Natural Products and Biosynthesis
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- Sulfur-Based Synthesis Techniques
- Catalytic C–H Functionalization Methods
- Cyclization and Aryne Chemistry
- Synthesis and Catalytic Reactions
- Microbial Metabolism and Applications
- Photochromic and Fluorescence Chemistry
- Alkaloids: synthesis and pharmacology
- Marine Sponges and Natural Products
- Chemical Reactions and Mechanisms
- Catalytic Cross-Coupling Reactions
- Carbohydrate Chemistry and Synthesis
- Enzyme Catalysis and Immobilization
- Crystallography and molecular interactions
- Advanced Synthetic Organic Chemistry
- Photoreceptor and optogenetics research
- Asymmetric Synthesis and Catalysis
- Cyclopropane Reaction Mechanisms
- Innovative Microfluidic and Catalytic Techniques Innovation
- FinTech, Crowdfunding, Digital Finance
University of Southern California
2023-2025
Harvard University Press
2024
Harvard University
2020-2024
Southern California University for Professional Studies
2023-2024
University of California, Los Angeles
2015-2020
University of California, Berkeley
2016
The akuammiline alkaloids are a family of natural products that have been widely studied for decades. Although notable synthetic achievements made recently, akuammilines possess methanoquinolizidine core evaded efforts. We report an asymmetric approach to these alkaloids, which has culminated in the first total syntheses (−)-2(S)-cathafoline and long-standing target (+)-strictamine. Moreover, enantioselective synthesis aspidophylline A is described.
Cross-electrophile couplings are influential reactions that typically require a terminal reductant or photoredox conditions. We discovered an iron-catalyzed reaction couples benzyl halides with disulfides to yield thioether products in the absence of and under The disclosed platform proceeds without sulfur-induced catalyst poisoning use exogenous base, supporting broad scope circumventing undesired elimination pathways. applied developed chemistry new mode disulfide bioconjugation, drug...
The advent of ultra-large libraries drug-like compounds has significantly broadened the possibilities in structure-based virtual screening, accelerating discovery and optimization high-quality lead chemotypes for diverse clinical targets. Compared to traditional high-throughput which is constrained approximately one million compounds, screening approach offers substantial advantages both cost time efficiency. By expanding chemical space with synthesized from easily accessible reproducible...
A precisely designed chiral squaramide derivative is shown to promote the highly enantioselective addition of trimethylsilyl bromide (TMSBr) a broad variety 3-substituted and 3,3-disubstituted oxetanes. The reaction provides direct general access synthetically valuable 1,3-bromohydrin building blocks from easily accessed achiral precursors. products are readily elaborated both by nucleophilic substitution through transition-metal-catalyzed cross-coupling reactions. catalytic oxetane ring...
The akuammiline alkaloids are a structurally diverse class of bioactive natural products isolated from plants found in various parts the world. A particularly challenging subset those that contain methanoquinolizidine core. We describe synthetic approach to these compounds has enabled first total syntheses (+)-strictamine, (−)-2(S)-cathafoline, (+)-akuammiline, and (−)-Ψ-akuammigine. Our strategy relies on development reductive interrupted Fischer indolization reaction construct common...
We report a facile method to synthesize stereodefined quaternary centers from reactions of arynes and related strained intermediates using β-ketoester-derived substrates. The conversion β-ketoesters chiral enamines is followed by reaction with in situ generated or cyclic alkynes. Hydrolytic workup provides the arylated alkenylated products enantiomeric excesses as high 96%. also describe one-pot β-ketoester substrate corresponding enantioenriched α-arylated product. Computations show how...
We present methods for β-selective 2-deoxy- and 2,6-dideoxyglucosylations of natural products, carbohydrates, amino acids using bis-thiourea hydrogen-bond-donor catalysts. Disarming ester protecting groups were necessary to counter the high reactivity 2-deoxyglycosyl electrophiles toward non-stereospecific S
Carbon–heteroatom bonds are of great importance due to their prevalence in pharmaceuticals, agrochemicals, materials, and natural products. Despite the effective use metal-catalyzed cross-coupling reactions between sp2-hybridized organohalides soft heteroatomic nucleophiles for carbon–heteroatom bond formation, sp3-hybridized remain limited coupling with thiols remains elusive. Here, we report benzyl or tertiary halides thiol catalyzed by iron extend utility alcohol amine nucleophiles. The...
Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving previously isolated or synthesized compounds largely completely untested. To address this issue, the Canvass library natural was assembled, in collaboration with academic industry researchers, quantitative high-throughput screening (qHTS) across a diverse set cell-based biochemical assays. Characterization...
Abstract Donor-acceptor Stenhouse adducts (DASAs) are molecular photoswitches spurring wide interest because of their dynamic photophysical properties, complex photoswitching mechanism, and diverse applications. Despite breakthroughs in modularity for the donor, acceptor, triene compartments, backbone heteroatom remains static due to synthetic challenges. We provide a predictive tool sought-after strategy vary heteroatom, introduce amino DASA photoswitches, analyze effects on properties....
Experimental and computational studies pertaining to the Fischer azaindolization reaction are reported. These explain why pyridylhydrazines poorly reactive in indolization reactions, addition origin of hydrazine substituent effects. Additionally, an interrupted variant methodology is disclosed, which provides a synthetic entryway into fused azaindoline scaffolds.
This account provides an overview of our laboratory’s studies unusual variant the Fischer indolization reaction. We describe discovery so-called ‘interrupted indolization’ and development reaction from a methodological standpoint. In addition, efforts to evaluate apply this methodology in context akuammiline alkaloid total synthesis are discussed. 1 Introduction 2 Interrupted Indolization Methodology 3 Applications Akuammiline Alkaloid Total Synthesis 4 Concluding Thoughts
Donor-acceptor Stenhouse adducts (DASAs) are molecular photoswitches that have spurred a decade of interest because their dynamic photophysical properties, complex photoswitching mechanism, and diverse applications. Despite breakthroughs in modularity for the donor, acceptor, triene compartments, backbone heteroatom has remained static due to synthetic challenges. We provide predictive tool sought-after strategy vary heteroatom, develop new subclass DASA photoswitches, analyze effects on...
Various metal catalysts have proven effective in carbon–heteroatom bond formation with softer heteroatomic nucleophiles, but examples remain largely limited to sp2 hybridized carbon electrophiles. Here, we report the coupling of sp3 benzyl or tertiary halides soft thiol nucleophiles catalyzed by iron. The reaction is broad substrate scope for both partners and applicable construction congested tri- tetrasubstituted carbon-centers as well beta-quaternary thioethers. synthetic utility further...
Abstract Metal-catalyzed cross-coupling reactions have transformed molecular synthesis. Although metal-catalyzed been used for cross-electrophile coupling reactions, they remain challenging due to homodimer formation. Recently, our group developed an iron-catalyzed of benzyl halides and disulfides produce thioethers without the use exogenous reductant or photoredox conditions, with undetectable levels elimination. This Synpacts article highlights both design strategy obviate detrimental...
Cross-electrophile couplings are influential reactions that typically require a terminal reductant or photoredox conditions. We discovered an iron-catalyzed reaction couples benzyl halide starting materials with disulfide building blocks to yield thioether products in the absence of and The disclosed platform proceeds without sulfur-induced catalyst poisoning use exogenous base, supporting broad scope circumventing undesired elimination pathways. applied developed chemistry new mode...
We present methods for β-selective 2-deoxy and 2,6-dideoxyglucosylations of natural products, carbohydrates, amino acids using bis-thiourea hydrogen-bond-donor catalysts. Disarming ester protecting groups were necessary to counter the high reactivity 2-deoxyglycosyl electrophiles toward non-stereospecific SN1 pathways. Alcohol phenol nucleophiles with both base- acid-sensitive functionalities compatible catalytic protocol, enabling access a wide array 2-deoxy-β-O-glucosides.
Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving previously isolated or synthesized compounds largely completely untested. To address this issue, the Canvass library natural was assembled, in collaboration with academic industry researchers, quantitative high-throughput screening (qHTS) across a diverse set cell-based biochemical assays. Characterization...
Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving previously isolated or synthesized compounds largely completely untested. To address this issue, the Canvass library natural was assembled, in collaboration with academic industry researchers, quantitative high-throughput screening (qHTS) across a diverse set cell-based biochemical assays. Characterization...