A5041600847- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Catalytic Alkyne Reactions
- Cyclopropane Reaction Mechanisms
- Crystallography and molecular interactions
- Chemical synthesis and alkaloids
- Synthesis and Reactivity of Heterocycles
- Synthesis and Biological Evaluation
- Synthesis and Reactions of Organic Compounds
- Alkaloids: synthesis and pharmacology
- Fluorine in Organic Chemistry
- Synthesis and biological activity
- Traditional and Medicinal Uses of Annonaceae
- Synthesis and Catalytic Reactions
- Synthesis of Organic Compounds
- Monoclonal and Polyclonal Antibodies Research
- Advanced biosensing and bioanalysis techniques
- Organic and Inorganic Chemical Reactions
- Asymmetric Synthesis and Catalysis
- Eicosanoids and Hypertension Pharmacology
- Catalytic C–H Functionalization Methods
- Organic Chemistry Cycloaddition Reactions
- Multicomponent Synthesis of Heterocycles
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2016-2023
Czech Academy of Sciences
2023
Columbia University
2021
Masaryk University
2009-2017
The development of reagents that can selectively react in complex biological media is an important challenge. Here we show N1-alkylation 1,2,4-triazines yields the corresponding triazinium salts, which are three orders magnitude more reactive reactions with strained alkynes than parent 1,2,4-triazines. This powerful bioorthogonal ligation enables efficient modification peptides and proteins. positively charged N1-alkyl salts exhibit favorable cell permeability, makes them superior for...
Fluorescent probes that light-up upon reaction with complementary bioorthogonal reagents are superior tools for no-wash fluorogenic bioimaging applications. In this work, a thorough study is presented on set of seventeen structurally diverse coumarin-tetrazine produce fluorescent dyes exceptional turn-on ratios when reacted trans-cyclooctene (TCO) and bicyclononyne (BCN) dienophiles. general, formation the fully aromatic pyridazine-containing resulting from BCN was found in terms...
Mitragynine (MG) is the most abundant alkaloid component of psychoactive plant material "kratom", which according to numerous anecdotal reports shows efficacy in self-medication for pain syndromes, depression, anxiety, and substance use disorders. We have developed a synthetic method selective functionalization unexplored C11 position MG scaffold (C6 indole numbering) via an indole-ethylene glycol adduct subsequent iridium-catalyzed borylation. Through this work we discover that represents...
Photochemical generation of dibenzosilacyclohept-4-yne 3 from the corresponding cyclopropenone 1 and its copper-free click reactions are reported. Steady-state irradiation, kinetic, transient absorption spectroscopy studies revealed that strained alkyne is rapidly (<5 ns) efficiently (Φ = 0.58–0.71) photoreleased undergoes remarkably fast, selective, high-yielding 1,3-dipolar cycloaddition with benzyl azide (∼20 M–1 s–1) or [4 + 2] inverse-electron-demand Diels–Alder reaction...
Fluorogenic bioorthogonal reactions enable visualization of biomolecules with excellent signal-to-noise ratio. A bicyclononyne-tetrazine ligation that produces fluorescent pyridazine products has been developed. In stark contrast to previous approaches, the formation dye is an inherent result chemical reaction and no additional fluorophores are needed in reagents. The crucial structural elements determine electron-donating groups present starting tetrazine unit. newly formed show interesting...
Fluorogenic bioorthogonal reactions enable visualization of biomolecules under native conditions with excellent signal-to-noise ratio. Here, we present the design and synthesis conformationally-strained aziridine-fused trans-cyclooctene (aza-TCO) dienophiles, which lead to formation fluorescent products in tetrazine ligations without need for attachment an extra fluorophore moiety. The presented aza-TCOs adopt highly strained "half-chair" conformation, was predicted computationally confirmed...
The development of abiotic chemical reactions that can be performed in an organelle-specific manner provide new opportunities drug delivery and cell biology. However, due to the complexity cellular environment, this remains a significant challenge. Here, we introduce structurally redesigned bioorthogonal tetrazine reagents spontaneously accumulate mitochondria live mammalian cells. attributes leading their efficient accumulation organelle were optimized include right combination...
Abstract Inverse‐electron‐demand Diels–Alder (iEDDA) cycloaddition between 1,2,4,5‐tetrazines and strained dienophiles belongs among the most popular bioconjugation reactions. In addition to its fast kinetics, this can be tailored produce fluorescent products from non‐fluorescent starting materials. Here we show that even reaction intermediates formed in iEDDA lead formation of new types fluorophores. The influence various substituents on their photophysical properties generality approach...
A straightforward synthesis of pyrimido[4,5-d]pyridazines from pyrimidines and tetrazines under basic conditions is reported. Deprotonated, substituted 5-halopyrimidines readily react with variously in a highly regioselective manner via complex reaction pathway, which was supported by DFT calculations. This mechanism leads to the empirically observed regioisomers without going through conceivable hetaryne intermediate. These results on led development methodology for preparation opposite...
The preparation of new non-symmetrical allenyl azines 5 with aliphatic and alicyclic substituents their reactions are described.When aldazines were refluxed in xylene formation bicyclic products 7 was observed.Compounds appeared as derivatives isowithasomnine.Combined intra-intermolecular criss-cross cycloadditions afforded heterocyclic 8 9 containing three fused five-membered rings.Structures all compounds elucidated by 1 H 13 C NMR, IR MS measurements some cases X-ray structure analysis.
Abstract Thermally initiated cycloaddition reactions of nonsymmetrical allenyl azines 1 with alkynes or other dipolarophiles usually lead to compounds three fused, five‐membered heterocyclic rings. With pronounced “push–pull” systems, however, the reaction ends formation substituted pyrrolidino[1,2‐ b ]pyrazoles 4 and, in case trifluoromethyl substitution, ring opening leads isolation 9 . Reaction mechanisms for these transformations are proposed. The molecular structures new heterocycles...
C-H activation of position 3 a substituted pyrazole ring catalyzed by palladium(II) was straightforward and convenient for arylated or heteroarylated 5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazoles. Moreover, we introduced simple protection the nitrogen in pyridin-2-yl directing group, which otherwise does not allow cross-coupling reaction, transformation to N-oxide. Selected final products were reasonably selective ALK5 kinase inhibitors.
Herein, we report a molecular framework design differing significantly from the traditional topology of proton sponges. We developed synthetic approach to preparation caged secondary amines by acid-catalyzed rearrangement fused tetracyclic heterocycles synthesized intramolecular criss-cross cycloaddition. Alkylation led air nonsensitive diazatetracyclo[4.4.0.13,10.15,8]dodecanes (DTDs) with rare alicyclic scaffolding in high overall yields. Their pKBH+ values were determined transprotonation...
A synthetic strategy to pyrrolo[2,1-f][1,2,4]triazines is reported. We show that various synthetically easily accessible 1,2,4-triazines can be efficiently alkylated under mild conditions provide the corresponding 1-alkyl-1,2,4-triazinium salts. These bench-stable salts serve as precursors triazinium ylides, which react in 1,3-dipolar cycloadditions with electron-poor dipolarophiles yield polysubstituted pyrrolotriazines a single step.
<p>Mitragynine is the most abundant alkaloid component of psychoactive plant material “kratom”, which according to numerous anecdotal reports shows efficacy in self-medication for pain syndromes, depression, anxiety, and substance use disorders. We developed a new synthetic method selective functionalization unexplored C11 position mitragynine scaffold (C6 indole numbering) via an indole-ethylene glycol adduct subsequent iridium-catalyzed borylation. discovered that represents key...
Abstract The development of reagents that can selectively react in complex biological media is an important challenge. Here we show N 1‐alkylation 1,2,4‐triazines yields the corresponding triazinium salts, which are three orders magnitude more reactive reactions with strained alkynes than parent 1,2,4‐triazines. This powerful bioorthogonal ligation enables efficient modification peptides and proteins. positively charged 1‐alkyl salts exhibit favorable cell permeability, makes them superior...
Mitragynine is the most abundant alkaloid component of psychoactive plant material “kratom”, which according to numerous anecdotal reports shows efficacy in self-medication for pain syndromes, depression, anxiety, and substance use disorders. We developed a new synthetic method selective functionalization unexplored C11 position mitragynine scaffold (C6 indole numbering) via an indole-ethylene glycol adduct subsequent iridium-catalyzed borylation. discovered that represents key locant...