A5029333564- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Radical Photochemical Reactions
- Innovative Microfluidic and Catalytic Techniques Innovation
- Sulfur-Based Synthesis Techniques
- Catalytic C–H Functionalization Methods
- Coordination Chemistry and Organometallics
- Synthesis and Reactivity of Heterocycles
- Nanomaterials for catalytic reactions
- Chemical Synthesis and Reactions
- Asymmetric Hydrogenation and Catalysis
- Advanced Photocatalysis Techniques
- Protein Degradation and Inhibitors
- Cyclopropane Reaction Mechanisms
- Fluorine in Organic Chemistry
- Oxidative Organic Chemistry Reactions
- Synthesis of heterocyclic compounds
- Mass Spectrometry Techniques and Applications
- Asymmetric Synthesis and Catalysis
- Chemical Synthesis and Analysis
- Molecular Spectroscopy and Structure
- Photoreceptor and optogenetics research
- Synthesis and Biological Evaluation
- Histone Deacetylase Inhibitors Research
- Advanced Chemical Physics Studies
Novartis (Switzerland)
2013-2025
Novartis Institutes for BioMedical Research
2022-2023
Universidade de Brasília
2002-2020
University of Cambridge
2016-2018
Massachusetts Institute of Technology
2016
Abstract We report herein a new method for the photoredox activation of boronic esters. Using these reagents, an efficient and high‐throughput continuous flow process was developed to perform dual iridium‐ nickel‐catalyzed C(sp 2 )–C(sp 3 ) coupling by circumventing solubility issues associated with potassium trifluoroborate salts. Formation adduct pyridine‐derived Lewis base found be essential Based on results we were able develop further simplified visible light mediated using esters cyano...
Abstract We report herein the use of a dual catalytic system comprising Lewis base catalyst such as quinuclidin‐3‐ol or 4‐dimethylaminopyridine and photoredox to generate carbon radicals from either boronic acids esters. This enabled wide range alkyl esters aryl react with electron‐deficient olefins via radical addition efficiently form C−C coupled products in redox‐neutral fashion. The was shown redox‐active complex trimeric (boroxines) solution.
In fragment-based drug discovery (FBDD), a weakly binding fragment hit is elaborated into potent ligand by bespoke functionalization along specific directions (growth vectors) from the core in order to complement 3D structure of target protein. This structure-based design approach can present significant synthetic challenges, as growth vectors often originate on sp2 or sp3 ring carbons which are not most synthetically accessible points fragment. To address this issue and expedite synthesis...
Many disease-relevant and functionally well-validated targets are difficult to drug. Their poorly defined 3D structure without deep hydrophobic pockets makes the development of ligands with low molecular weight high affinity almost impossible. For these targets, incorporation into a ternary complex may be viable alternative modulate in most cases inhibit their function. Therefore, we interested methods identify characterize glues. In protein array screen 50 different macrocyclic FKBP12...
We report an acridium-based organic photocatalyst as efficient replacement for iridium-based photocatalysts to oxidise boronic acid derivatives by a single electron process. Furthermore, we applied the developed catalytic system synthesis of four active pharmaceutical ingredients (APIs). A straightforward scale up approach using continuous flow photoreactors is also reported affording gram hour throughput.
Abstract A general, efficient method for C−N cross‐coupling has been developed using N , ‐dimethyloctanamide as a catalytic cosolvent biphasic continuous‐flow applications. The described was used to generate variety of biarylamines and integrated into two‐step sequence which converted phenols via either triflates or tosylates. Additionally, the applied three‐step synthesis imatinib, API Gleevec, in good yield without need solvent switches.
Abstract We report herein a new method for the photoredox activation of boronic esters. Using these reagents, an efficient and high‐throughput continuous flow process was developed to perform dual iridium‐ nickel‐catalyzed C(sp 2 )–C(sp 3 ) coupling by circumventing solubility issues associated with potassium trifluoroborate salts. Formation adduct pyridine‐derived Lewis base found be essential Based on results we were able develop further simplified visible light mediated using esters cyano...
Abstract We report herein the use of a dual catalytic system comprising Lewis base catalyst such as quinuclidin‐3‐ol or 4‐dimethylaminopyridine and photoredox to generate carbon radicals from either boronic acids esters. This enabled wide range alkyl esters aryl react with electron‐deficient olefins via radical addition efficiently form C−C coupled products in redox‐neutral fashion. The was shown redox‐active complex trimeric (boroxines) solution.
An efficient and scalable transformation of 3-halo-N-acyl anilines to the corresponding benzoxazoles within a continuous flow reactor is reported. This proceeds via base-mediated deprotonation, ortho-lithiation, intramolecular cyclization provide unstable lithiated benzoxazole moieties. The subsequent in-line electrophilic quench results in formation substituted high yield quality. Continuous technology allowed for accurate temperature control immediate while minimizing hold-up time...
Photoaffinity labeling is a widely used technique for studying ligand-protein and protein-protein interactions. Traditional photoaffinity labels utilize nonspecific C-H bond insertion reactions mediated by highly reactive intermediate. Despite being the most labels, diazirines exhibit limited compatibility with downstream organic suffer from storage stability concerns. This study introduces oxadiazolines as innovative complementary photoactivatable addition to toolbox demonstrates their...
The focus of this study was to develop a chemical reaction sequence toward key benzoxazole building block, required for clinical manufacturing lead candidate in the respiratory disease area. chemistry consisted initial low-temperature reactions with an organometallic reagent generate core, and followed by noncryogenic transformations sulfonamide substituent. With particular interest continuous-flow we attempted integrate entire on lab scale. Subsequent in-depth process research, supported...
DFT-calculations allow prediction of the reactivity uncommon N-heterocyclic scaffolds pyrazolo[1,5-a]pyrimidines and imidazo[1,2-b]pyridazines considerably facilitate their functionalization. The derivatization these N-heterocycles was realized using Grignard reagents for nucleophilic additions to 5-chloropyrazolo[1,5-a]pyrimidines TMP
Herein, we disclose the first regio-, site- and chemoselective late-stage (hetero)aryl C-H bond cyclopropenylation with cyclopropenium cations (CPCs). The process is fast, operationally simple shows an excellent functional group tolerance in densely-functionalized drug molecules, natural products, agrochemicals fluorescent dyes. Moreover, discovered that installation of cyclopropene ring molecules could not only be used to shield against metabolic instability but also as a synthetic tool...
A general, efficient method for C−N cross-coupling has been developed using N,N-dimethyloctanamide as a catalytic cosolvent biphasic continuous-flow applications. The described was used to generate variety of biarylamines and integrated into two-step sequence which converted phenols via either triflates or tosylates. Additionally, the applied three-step synthesis imatinib, API Gleevec, in good yield without need solvent switches.
An enabling continuous flow setup for handling of unstable organolithium intermediates and synthesis heteroaryl sulfinates on a multigram scale is described. The developed process allows the simple isolation which are otherwise challenging to access in classical batch mode. lithium sulfinate salts prepared by this method were shown be efficient reaction partners palladium catalyzed C(sp2)-C(sp2) cross-coupling medicinally relevant bis-heteroaryl motifs.
Continuous Flow methods to access glyoxal derivatives, which serve as valuable precursors for heterocyclic chemistry.
We report the selective functionalization of 1H-imidazo[1,2-b]pyrazole scaffold using a Br/Mg-exchange, as well regioselective magnesiations and zincations with TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl), followed by trapping reactions various electrophiles. In addition, we fragmentation pyrazole ring, giving access to push-pull dyes proaromatic (1,3-dihydro-2H-imidazol-2-ylidene)malononitrile core. These methods were used in synthesis an isostere indolyl drug pruvanserin. Comparative...
Straightforward calculations such as determinations of pKa values and N-basicities have allowed the development a set organometallic reactions for regioselective functionalization underexplored fused N-heterocycle imidazo[1,2-a]pyrazine. Thus, metalations 6-chloroimidazo[1,2-a]pyrazine using TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl) TMPMgCl·LiCl TMP2Zn·2MgCl2·2LiCl provided Zn- Mg-intermediates, that after quenching with various electrophiles gave access to polyfunctionalized...
In this note we propose an alternative approach to the experimental study of Hooke’s law that takes into account variation elastic constant as a function initial length spring. We also present adequate methodology develop analysis graphics students will obtain in laboratory when they follow new method suggested here.
Abstract The analysis of amino acid fragmentation is promising in the search for living organisms other planets, which could be investigated by just scanning specific fragments their upper atmosphere using advanced spectroscopy techniques. Motivated this possibility, we develop here a Density Functional Theory ( DFT )‐based protocol to investigate an essential constituent cells: L‐cysteine acid. After determining structural and energetics neutral single ionized conformers good agreement with...
Abstract Treatment of substrates (I) with BuLi under continuous flow conditions allows to minimize the hold‐up time for resulting unstable lithiated benzoxazole intermediates which react various electrophiles give corresponding substituted benzoxazoles.
Abstract Herein, we disclose the first regio‐, site‐ and chemoselective late‐stage (hetero)aryl C−H bond cyclopropenylation with cyclopropenium cations (CPCs). The process is fast, operationally simple shows an excellent functional group tolerance in densely‐functionalized drug molecules, natural products, agrochemicals fluorescent dyes. Moreover, discovered that installation of cyclopropene ring molecules could not only be used to shield against metabolic instability but also as a synthetic...