A5102868038- Asymmetric Synthesis and Catalysis
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Asymmetric Hydrogenation and Catalysis
- Radical Photochemical Reactions
- Catalytic C–H Functionalization Methods
- Synthetic Organic Chemistry Methods
- Chemical Synthesis and Analysis
- Chemical synthesis and alkaloids
- Sulfur-Based Synthesis Techniques
- Fluorine in Organic Chemistry
- Crystallography and molecular interactions
- Analytical Chemistry and Chromatography
- Organic Chemistry Cycloaddition Reactions
- Catalytic Cross-Coupling Reactions
- Chemical Reactions and Isotopes
- Chemical Synthesis and Reactions
- Oxidative Organic Chemistry Reactions
- Monoclonal and Polyclonal Antibodies Research
- Chemical Reaction Mechanisms
- Click Chemistry and Applications
- Advanced Synthetic Organic Chemistry
- Alkaloids: synthesis and pharmacology
- Plant-based Medicinal Research
- Catalytic Processes in Materials Science
Princeton University
2015-2025
California Institute of Technology
2001-2005
University of California, Berkeley
2000-2001
University of California, Irvine
2001
A strategy for cross-electrophile coupling has been developed via the merger of photoredox and transition metal catalysis. In this report, we demonstrate use commercially available tris(trimethylsilyl)silane with metallaphotoredox catalysis to efficiently couple alkyl bromides aryl or heteroaryl in excellent yields. We hypothesize that a photocatalytically generated silyl radical species can perform halogen-atom abstraction activate halides as nucleophilic cross-coupling partners. This...
The direct application of carboxylic acids as a traceless activation group for radical Michael additions has been accomplished via visible light-mediated photoredox catalysis. Photon-induced oxidation broad series acids, including hydrocarbon-substituted, α-oxy, and α-amino provides versatile CO2-extrusion platform to generate donors without the requirement organometallic or propagation. A diverse array acceptors is amenable this new conjugate addition strategy. An technology three-step...
Pyrroloindoline and bispyrroloindoline are a subclass of alkaloid structural motifs that commonly exhibit biological activity. An enantioselective organocatalytic approach to the synthesis pyrroloindoline architecture is described. The addition–cyclization tryptamines with α,β-unsaturated aldehydes in presence imidazolidinone catalysts 1 8 provides adducts high yield excellent enantioselectivities. This transformation successful for wide range tryptamine aldehyde substrates. amine-catalyzed...
Abstract The direct decarboxylative arylation of α‐oxo acids has been achieved by synergistic visible‐light‐mediated photoredox and nickel catalysis. This method offers rapid entry to aryl alkyl ketone architectures from simple acid precursors via an acyl radical intermediate. Significant substrate scope is observed with respect both the oxo arene coupling partners. mild can also be utilized efficiently access medicinal agents, as demonstrated synthesis fenofibrate.
The first organocatalytic enantioselective radical polycyclization has been accomplished using singly occupied molecular orbital (SOMO) catalysis. presented strategy relies on a selective single-electron oxidation of chiral enamines formed by condensation polyenals with an imidazolidinone catalyst employing suitable copper(II) oxidant. reaction proceeds under mildly acidic conditions at room temperature and shows compatibility array electron-poor as well electron-rich functional groups. Upon...
A concise and highly enantioselective total synthesis of the akuammiline alkaloid (−)-vincorine has been accomplished. key element is a stereoselective organocatalytic Diels–Alder, iminium cyclization cascade sequence, which serves to construct tetracyclic core architecture in one step from simple achiral precursors. The challenging seven-membered azepanyl ring system installed by way single electron-mediated event initiated an acyl telluride precursor. achieved nine steps 9% overall yield...
A generic activation mode for asymmetric LUMO-lowering catalysis has been developed using the long-established principles of oxy-allyl cation chemistry. Here, enantioselective conversion racemic α-tosyloxy ketones to optically enriched α-indolic carbonyls accomplished a new amino alcohol catalyst in presence electron-rich indole nucleophiles. Kinetic studies reveal that rate-determining step this S(N)1 pathway is catalyst-mediated ketone deprotonation form an enantiodiscriminant prior...
The elucidation of protein interaction networks is critical to understanding fundamental biology as well developing new therapeutics. Proximity labeling platforms (PLPs) are state-of-the-art technologies that enable the discovery and delineation biomolecular through identification protein-protein interactions. These work via catalytic generation reactive probes at a biological region interest; these then diffuse solution covalently “tag” proximal biomolecules. physical distance determines...
Abstract Peptides play critical roles in cellular functions such as signaling and immune regulation, peptide-based biotherapeutics show great promise for treating various diseases. Among these, cell-penetrating peptides (CPPs) are particularly valuable drug delivery due to their ability cross cell membranes. However, the mechanisms underlying CPP-mediated transport, especially across blood-brain barrier (BBB), remain poorly understood. Mapping intracellular CPP pathways is essential...
A highly selective method for the synthesis of asymmetrically substituted carbocycles and heterocycles from unactivated aldehyde-olefin precursors has been achieved via enantioselective SOMO-catalysis. Addition a catalytically generated enamine radical cation across pendent olefin serves to establish general asymmetric strategy toward production wide range formyl-substituted rings with alkene transposition. Conceptually, this novel mechanism allows direct access "homo-ene"-type products.
Wet chemistry: Organo-SOMO activation is an intricate process. The catalyst deactivated in the absence of H2O and its concentration maintained with 2 equivalents H2O. kinetic role ceric ammonium nitrate (CAN) masked by phase transfer limited solubility enhanced added Mechanistic studies show that careful addition to dried reagents greatly enhances reaction. TMS=trimethylsilyl.
Abstract Teamarbeit : Die kombinierte Anwendung von Iminium(Im)‐ und Enamin(En)‐Katalysatoren ermöglicht eine Vielzahl an wertvollen asymmetrischen Umwandlungen, darunter die 1,2‐Hydroaminierung, 1,2‐Hydrooxidation 1,2‐Aminooxidation Olefinen (siehe Bild). Eine enantioselektive Organokaskadenkatalyse wurde auch für Synthese eines komplexen Naturstoffs genutzt. magnified image
Abstract Proximity labeling traditionally identifies interactomes of a single protein or RNA, though this approach limits mechanistic understanding biomolecules functioning within complex systems. Here, we demonstrate strategy for deciphering ligand-induced changes to global biomolecular interactions by enabling proximity labelling at the mesoscale, across an entire cellular system. By inserting nanoscale catalysts throughout chromatin, system, MesoMap, provided new insights into how HDAC...
Many disease states can be understood by elucidating small-scale biomolecular protein interaction networks, or microenvironments. Recently, photoproximity labeling methods, like µMap, have emerged as high-resolution techniques to study key spatial relationships in subcellular architectures. However, vitro models typically lack cell type heterogeneity and three dimensionality, integral parameters that limit the translation of findings clinic. To this end, formalin-fixed paraffin-embedded...
Depending upon the nature of alkene and allylic substituents, acid-promoted rearrangements acetals derived from anti diols give 12 or stereoisomeric acyltetrahydrofurans 13. Stereoelectronic effects substituents extent bonding in Prins cyclization transition state are central features a proposed new model for predicting stereoselection Prins-pinacol synthesis acyltetrahydrofurans.
Antibody drug conjugates (ADCs), which feature a monoclonal antibody (mAb) for cell targeting linked to cytotoxic payload killing, are remarkably effective class of targeted therapeutics. Despite their success, however, ADCs typically rely on highly potent payloads, precluding the use less payloads and broader range mechanisms action (MoA).1-4 Moreover, emerging perspective that passive play roles in ADC function vivo suggests opportunities engineer new based stable prodrug scaffolds with...