A5076989067- Cyclization and Aryne Chemistry
- Catalytic Alkyne Reactions
- Chemical synthesis and alkaloids
- Crystallization and Solubility Studies
- Synthesis and pharmacology of benzodiazepine derivatives
- X-ray Diffraction in Crystallography
- Chemical Reactions and Mechanisms
- Synthetic Organic Chemistry Methods
- Protein Degradation and Inhibitors
- Chemical Reaction Mechanisms
- Multiple Myeloma Research and Treatments
- Renal Diseases and Glomerulopathies
- Cholinesterase and Neurodegenerative Diseases
- Microbial metabolism and enzyme function
- Mesenchymal stem cell research
- Cytokine Signaling Pathways and Interactions
- Psoriasis: Treatment and Pathogenesis
- Alkaloids: synthesis and pharmacology
- Synthesis and Properties of Aromatic Compounds
- Catalytic C–H Functionalization Methods
- Synthesis and Catalytic Reactions
- Advanced Breast Cancer Therapies
- Retinoids in leukemia and cellular processes
- Synthesis of Indole Derivatives
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
Maze (United States)
2022-2023
University of California, Los Angeles
2009-2014
California Institute of Technology
2013-2014
Pasadena City College
2014
Division of Chemistry
2014
California State University Los Angeles
2014
University of Iowa
2004-2007
Density functional theory computations reproduce the surprisingly high regioselectivities in nucleophilic additions and cycloadditions to 4,5-indolynes low reactions of 5,6-indolynes. Transition-state distortion energies control regioselectivities, activating 5 6 positions over 4 7 positions, leading preferences for 5- 6-substituted products from 4,5- 6,7-indolynes, respectively. Orbital electrostatic interactions have only minor effects, producing The model predicts with 6,7-indolynes;...
Efficient syntheses of 4,5-, 5,6-, and 6,7-indolyne precursors beginning from commercially available hydroxyindole derivatives are reported. The synthetic routes versatile allow access to indolyne that remain unsubstituted on the pyrrole ring. Indolynes can be generated under mild fluoride-mediated conditions, trapped by a variety nucleophilic reagents, used number novel substituted indoles. Nucleophilic addition reactions indolynes proceed with varying degrees regioselectivity; distortion...
We report the design and synthesis of an indolyne that displays a reversal in regioselectivity, both nucleophilic addition cycloaddition reactions, compared to typical 4,5-indolynes. Our approach utilizes simple computations predict regioselectivity reactions unsymmetrical arynes. With this methodology, novel benzenoid-substituted indoles can be accessed with significant regiocontrol. Furthermore, technology provides unconventional tactic for C4-substituted indole alkaloids, as demonstrated...
We report an experimental and computational study of 3-silylarynes. The addition nucleophiles yield ortho-substituted products as a result aryne distortion, but meta-substituted form predominately when the nucleophile is large. Computations correctly predict preferred site attack observed in both nucleophilic cycloaddition experiments. Nucleophilic additions to 3-tert-butylbenzyne, which not significantly distorted, give products.
Think before you act: A computational approach is reported for evaluating the synthetic potential of heterocyclic arynes. Routine and rapid calculations arene dehydrogenation energies aryne angle distortion predict likelihood that a given hetaryne can be generated, as well degree regioselectivity expected in reaction between nucleophilic trapping agent (see picture). Detailed facts importance to specialist readers are published "Supporting Information". Such documents peer-reviewed, but not...
Inhibition of the bromodomain transcriptional regulator CBP/P300 is an especially interesting new therapeutic approach in oncology. We recently disclosed vivo chemical tool 1 (GNE-272) for CBP that was moderately potent and selective over BRD4(1). In pursuit a more inhibitor, we used structure-based design. Constraining aniline into tetrahydroquinoline motif maintained potency increased selectivity 2-fold. Structure–activity relationship studies coupled with further design targeting LPF...
A mild method to access a variety of substituted indole derivatives has been developed. The strategy relies on the generation highly reactive indolyne intermediates, which function as electrophilic surrogates.
We report the total syntheses of (−)-indolactam V and C7-substituted indolactam alkaloids (−)-pendolmycin, (−)-lyngbyatoxin A, (−)-teleocidin A-2. The strategy for preparing relies on a distortion-controlled indolyne functionalization reaction to establish C4–N linkage, in addition an intramolecular conjugate build conformationally-flexible nine-membered ring. synthesis then sets stage divergent other targeted alkaloids. Specifically, late-stage sp2–sp3 cross-couplings derivative are used...
An efficient procedure for the gram-scale preparation of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate, a versatile precursor to o-benzyne, is presented. The three-step sequence utilizes phenol as starting material, requires only one chromatographic purification, and ultimately delivers desired silyltriflate in 66% overall yield.
A new strategy to access linear amines from terminal olefin precursors is reported. This two-step, one-pot hydroamination methodology employs sequential oxidation and reduction catalytic cycles. The formal transformation proceeds with excellent regioselectivity, only the anti-Markovnikov product observed. Up 70% yield can be obtained styrenes or aliphatic olefins either primary secondary aromatic amines. Additionally, scope broad respect accommodates a variety of functionalities; we...
A series of cyclometalated <italic>Z</italic>-selective ruthenium olefin metathesis catalysts with alterations to the N-heterocyclic carbene (NHC) ligand were prepared.
A transition-metal-free methodology for the construction of pharmaceutically relevant tertiary aminocyclopropanes is reported. Hydrazonamides, safe and stable carbene precursors, undergo smooth cyclopropanation with vinyl arenes in presence a base. The reaction proceeds stereoselectivity to favor Z isomer provides facile access variety substitution patterns through variation coupling partners.
Heterocyclic arynes hold much promise for applications in modern synthetic chemistry. One particular class of hetarynes is those derived from the indole heterocycle (i.e., indolynes). Indolynes can be generated under mild fluoride-based reaction conditions using silyltriflate precursors. Indolyne-trapping experiments provide access to benzenoid-substituted indoles a controlled manner with synthetically useful yields. Regioselectivities predicted prior simple calculations, ultimately allowing...
Erst denken, dann handeln: Ein theoretischer Ansatz zur Bestimmung des Synthesepotenzials heterocyclischer Arine wird vorgestellt. Mit schnellen Routinerechnungen der Dehydrierungsenergien von Arenen sowie Winkelverzerrung Arinen können die Wahrscheinlichkeit, mit ein Arin gebildet wird, und Grad Regioselektivität, bei Reaktion Heteroarins einem Nukleophil zu erwarten ist, vorausgesagt werden (siehe Bild). Detailed facts of importance to specialist readers are published as "Supporting...
The epigenetic regulator CBP/P300 presents a novel therapeutic target for oncology. Previously, we disclosed the development of potent and selective CBP bromodomain inhibitors by first identifying pharmacophores that bind KAc region then building into LPF shelf. Herein, report "hybridization" variety KAc-binding fragments with tetrahydroquinoline scaffold makes optimal interactions shelf, imparting enhanced potency selectivity to hybridized ligand. To demonstrate utility our hybridization...
Epidermal progenitor cells (EpPCs) were long thought to be unipotent, giving rise only other keratinocytes but recent studies question this assumption. Here, we investigated whether mouse EpPCs can adopt antigenic and functional phenotypes. To test this, injected freshly isolated cultured transient amplifying into diabetic non-diabetic ischemic hindlimb followed the cells' fate recovery of limb blood flow over time. Both incorporated vasculature 2 5 weeks post-injection, some expressed...
A cascade benzyne Fries rearrangement is reported that offers facile access to 2,3-disubstituted phenols, allowing for two points of diversity on the adduct. The methodology utilizes an <i>o</i>-(trimethylsilyl)triflate phenol as a common intermediate, from which substitution phenolic oxygen readily yields precursors undergo requisite in presence amine nucleophile, base, and fluoride source.