A5052796093- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Asymmetric Hydrogenation and Catalysis
- Catalytic C–H Functionalization Methods
- Radical Photochemical Reactions
- Click Chemistry and Applications
- Synthetic Organic Chemistry Methods
- Asymmetric Synthesis and Catalysis
- Chemical Synthesis and Analysis
- Fluorine in Organic Chemistry
- Advanced Synthetic Organic Chemistry
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Synthesis and Catalytic Reactions
- Carbohydrate Chemistry and Synthesis
- Advanced biosensing and bioanalysis techniques
- Cancer-related Molecular Pathways
- Immunotherapy and Immune Responses
- Analytical chemistry methods development
- Catalytic Cross-Coupling Reactions
- Oxidative Organic Chemistry Reactions
- Surface Chemistry and Catalysis
- Alkaloids: synthesis and pharmacology
- Bioactive natural compounds
- Biotin and Related Studies
Massachusetts Institute of Technology
2022-2023
ETH Zurich
2016-2019
Board of the Swiss Federal Institutes of Technology
2017
ConspectusThe catalytic, asymmetric synthesis of complex molecules has been a core focus our research program for some time because developments in the area can have an immediate impact on identification novel strategies value-added molecules. In concert with this central interest, we emphasized design ligand scaffolds as tactic to discover and develop chemistry overcome well-recognized synthetic challenges. Based group's work chiral pool-derived diolefin ligands, designed implemented class...
Experimental mechanistic studies of iridium-catalyzed, enantioselective allylic substitution enabled by (phosphoramidite,olefin) ligands are reported. (η2-Allylic alcohol)iridium(I) and (η3-allyl)iridium(III) complexes were synthesized characterized NMR spectroscopy as well X-ray crystallography. The substrate catalytically kinetically competent to be intermediates in substitutions branched, racemic alcohols with various nucleophiles. In addition, we have identified an off-cycle pathway...
Abstract Electron‐transfer photocatalysis provides access to the elusive and unprecedented N ‐pyridyl radical cation from selected N‐substituted pyridinium reagents. The resulting C(sp 2 )−H functionalization of (hetero)arenes furnishes versatile intermediates for development valuable aminated aryl scaffolds. Mechanistic studies that include first spectroscopic evidence a spin‐trapped adduct implicate SET‐triggered, pseudo‐mesolytic cleavage N−X reagents mediated by visible light.
Iridium-(P,olefin) complex-catalyzed enantio- and diastereoselective formation of substituted spiroketals from racemic, allylic carbonates is reported, which enables the installation multiple stereogenic centers in a single operation. The protocol was effective for preparation collection various ring sizes substituents, including heteroatoms with high diastereoselectivity. Furthermore, cascade reactions that couple this transformation to additional reversible processes have been achieved...
An enantioconvergent C(sp3)–C(sp3) coupling between racemic allenylic electrophiles and alkylzinc reagents has been developed. Ir/(phosphoramidite,olefin) catalyst provides access to highly enantioenriched substitution products (93–99% ee) with complete regiocontrol (>50:1 rr in all cases) over the corresponding 1,3-diene isomers which are obtained predominantly when other metal catalysts emplyed. The synthetic utility of was highlighted a variety stereoselective transition metal-catalyzed...
Encoding small-molecule information in DNA has been leveraged to accelerate the discovery of ligands for therapeutic targets such as proteins. However, oligonucleotide-based encoding is hampered by inherent limitations stability and density. In this study, we establish abiotic peptides next-generation storage apply them diverse synthesis. The chemical peptide-based tag allows use palladium-mediated reactions efficiently synthesize peptide-encoded libraries (PELs) with broad diversity high...
Abstract Electron‐transfer photocatalysis provides access to the elusive and unprecedented N ‐pyridyl radical cation from selected N‐substituted pyridinium reagents. The resulting C(sp 2 )−H functionalization of (hetero)arenes furnishes versatile intermediates for development valuable aminated aryl scaffolds. Mechanistic studies that include first spectroscopic evidence a spin‐trapped adduct implicate SET‐triggered, pseudo‐mesolytic cleavage N−X reagents mediated by visible light.
Abstract Morpholine ketene aminal is employed in iridium‐catalyzed asymmetric allylic alkylation reactions as a surrogate for amide enolates to prepare γ,δ‐unsaturated β‐substituted morpholine amides. Kinetic resolution or, alternatively, stereospecific substitution affords the corresponding products high enantiomeric excess. The utility of generated by this method has been showcased their further elaboration into amines, ketones, or acyl silanes. A putative catalytic intermediate (η 3...
Abstract In diesem Aufsatz sind die jüngsten Fortschritte beim Verständnis und Design von N‐funktionalisierten Pyridiniumsalzen als redoxaktivierte Einelektronentransfer‐Reagenzien zur Übertragung funktioneller Gruppen zusammengefasst. Anhand einer Auswahl an repräsentativen Methoden werden Reaktivität grundlegende in sich rasch entwickelnden Bereich diskutiert. Diese Reagenzien weisen zwei grundsätzlich divergierende Reaktionspfade auf: homolytische Fragmentierung Freisetzung des...
Herein, the first total synthesis and stereochemical assignment of (+)-broussonetine H are reported. The ambiguous stereocenters within different fragments were independently installed through asymmetric methods, namely a diastereo- enantioselective, iridium-catalyzed spiroketalization Brown allylation. Finally, convergent merging enabled all potential diastereomers, allowing H.
Aiming at developing mechanism-based amino acid (18)F-PET tracers for tumor imaging, we synthesized two (18)F-labeled analogues of 5-hydroxy-l-[β-(11)C]tryptophan ([(11)C]5HTP) whose excellent in vivo performance neuroendocrine tumors is mainly attributed to its decarboxylation by aromatic decarboxylase (AADC), an enzyme overexpressed these malignancies. Reference compounds and precursors were following multistep synthetic approaches. Radiosynthesis was accomplished good radiochemical yields...
Protein–protein interactions (PPIs) are intriguing targets in drug discovery and development. Peptides well suited to target PPIs, which typically present with large surface areas lacking distinct features deep binding pockets. To improve these topologies advance the development of PPI-focused therapeutics, potential ligands can be equipped electrophilic groups enable through covalent mechanisms action. We report a strategy termed electrophile scanning identify reactivity hotspots known...
Molecular vaccines comprising antigen peptides and inflammatory cues make up a class of therapeutics that promote immunity against cancer pathogenic diseases but often exhibit limited efficacy. Here, we engineered an peptide delivery system to enhance vaccine efficacy by targeting dendritic cells mediating cytosolic delivery. The consists the nontoxic anthrax protein, protective (PA), single-chain variable fragment (scFv) recognizes XCR1 receptor on (DCs). Combining these proteins enabled...
Protein–protein interactions (PPIs) are intriguing targets in drug discovery and development. Peptides well suited to target PPIs, which typically present with large surface areas lacking distinct features deep binding pockets. To improve these topologies by PPI-focused therapeutics advance their development, potential ligands can be equipped electrophilic groups enable through covalent mechanisms of action. We report a strategy termed electrophile scanning identify reactivity hotspots known...
Abstract Morpholine ketene aminal is employed in iridium‐catalyzed asymmetric allylic alkylation reactions as a surrogate for amide enolates to prepare γ,δ‐unsaturated β‐substituted morpholine amides. Kinetic resolution or, alternatively, stereospecific substitution affords the corresponding products high enantiomeric excess. The utility of generated by this method has been showcased their further elaboration into amines, ketones, or acyl silanes. A putative catalytic intermediate (η 3...