A5071592912- Organoboron and organosilicon chemistry
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- Catalytic C–H Functionalization Methods
- Catalytic Cross-Coupling Reactions
- Synthetic Organic Chemistry Methods
- Asymmetric Synthesis and Catalysis
- Synthesis and Catalytic Reactions
- Crystallography and molecular interactions
- Asymmetric Hydrogenation and Catalysis
- Phytoestrogen effects and research
- Cyclopropane Reaction Mechanisms
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Biochemical effects in animals
- Catalytic Alkyne Reactions
- Advanced Synthetic Organic Chemistry
- Protein Degradation and Inhibitors
- Chemical Synthesis and Reactions
- Protein Tyrosine Phosphatases
- Chemical synthesis and alkaloids
- Synthesis and Biological Activity
- Organophosphorus compounds synthesis
- HIV/AIDS drug development and treatment
University of Toronto
2012-2017
Korea Institute of Radiological and Medical Sciences
2016
Cliniques Universitaires Saint-Luc
2016
Davenport University
2014-2016
McGill University
2012-2015
Toronto Public Health
2015
Unité de catalyse et de chimie du solide de Lille
2014
Catalyse
2014
Universidade de Vigo
2013
Niagara University
2009-2010
Excellent tolerance: Stable acylboronates equipped with N-methyliminodiacetyl (MIDA) boryl groups ([B]) were prepared by using a sequence of oxidative manipulations at the boron-bound carbon center (green in scheme). Chemoselective transformations these acylated organoboron building blocks yielded range multifunctionalized boron derivatives and supplied access to valuable borylated heterocycles (see Organoboronic acids their are widely utilized chemical synthesis.1 The reactivity molecules...
A reaction exemplifying migration of boron-substituted carbon is described. We show that α-boroalkyl groups transient boroalkyl acyl azide intermediates readily migrate from to nitrogen. This process allows access a new class stable molecules, α-boryl isocyanates, α-borylcarboxylic acid precursors. The methodology facilitates synthesis wide range α-aminoboronic derivatives, including α,α-disubstituted analogues.
Herein, we describe the bromomethyl acyl boronate linchpin--an enabling reagent for condensation-driven assembly of novel bis(heteroaryl) motifs. This building block is readily accessible from commercially available starting materials. A variety 2-amino- and 2-methylpyridines were reacted with MIDA-protected acylboronate to afford 2-boryl imidazo[1,2-a]pyridine indolizine derivatives, respectively, in excellent yields. Subsequent condensation hydroxyamidines hydrazonamides converted...
Described herein is the preparation of oxalyl boronate building blocks and their application for construction heterocycles. The unit, readily accessible through commercially available starting materials, enables a modular approach synthesis imidazoles. A variety aromatic, heteroaromatic, alkyl carboxaldehydes were condensed with boronates to afford substituted boryl imidazoles in regiocontrolled fashion. Subsequent palladium-catalyzed cross-coupling haloarenes furnished desired...
Abstract Herein, we demonstrate the use of α‐boryl aldehydes and acyl boronates in synthesis aminoboronic acid derivatives. This work highlights untapped potential boron‐substituted iminium ions offers insights into behavior N ‐methyliminodiacetyl (MIDA) during condensation tautomerization processes. The preparative value this contribution lies demonstration that various amines, including linear cyclic peptides, can be readily conjugated with boron‐containing fragments. A mild deprotection...
The use of α-boryl enamine and enamide linchpins in the synthesis nitrogen heterocycles has been demonstrated. Boryl enamines provide ready access to corresponding α-halo aldehydes, which undergo regioselective annulation form borylated thiazoles. A condensation/amidation sequence converts aldehydes into stable enamides without concomitant C → N migration. We also show that palladium-catalyzed cyclization leads synthetically versatile isoindolones. These molecules can be subsequently used...
Pairing of mutually reactive functional groups in the same molecule affords enabling opportunities chemical synthesis. Kinetically amphoteric molecules exemplify this scenario and help avoid pitfalls protecting-group chemistry by exploiting innate reactivity groups. In perspective, we highlight recent development MIDA (N-methyliminodiacetyl) α-boryl aldehydes as building blocks that act linchpins synthesis heterocycles. This short review includes topics ranging from metal-catalyzed...
Inhibition of murine double minute 2 (MDM2)-p53 protein-protein interaction with small molecules has been shown to reactivate p53 and inhibit tumor growth. Here, we describe rational, structure-guided, design novel isoindolinone-based MDM2 inhibitors. X-ray crystallography, quantum mechanics ligand-based design, metabolite identification all contributed toward the discovery potent
The development of a palladium-catalyzed sp(3)-sp(2) Suzuki-Miyaura cross-coupling B-alkyl-N-methyliminodiacetyl (B-alkyl MIDA) boronates and (hetero)aryl bromides is reported. This transformation tolerant variety functional groups (F, NO2, CN, Cl, COCH3, CHO). B-Alkyl MIDA allow an efficient reaction directed toward the synthesis unsymmetrical methylene diaryls as well alkylated arenes in good to excellent yields.
The ubiquitously expressed protein tyrosine phosphatase SHP2 is required for signaling downstream of receptor kinases (RTKs) and plays a role in regulating many cellular processes. Genetic knockdown pharmacological inhibition suppresses RAS/MAPK inhibit the proliferation RTK-driven cancer cell lines. Here, we describe first reported fragment-to-lead campaign against SHP2, where X-ray crystallography biophysical techniques were used to identify fragments binding multiple sites on SHP2....
Vicinal aziridine-containing diamines have been obtained with high syn-stereoselectivity from readily available aziridine aldehyde dimers in the Petasis borono-Mannich reaction. Subsequent solvent- and/or nucleophile-dependent ring-opening of ring yields functionalized 1,2- and 1,3-diamines regioselectivity. The opening is also influenced by substitution at C3 position aziridine. A mechanistic rationale for highly syn-selective three-component reaction proposed.
Tolerant: Stabile Acylboronate mit MIDA-Borylgruppen (MIDA=N-Methyliminodiacetyl; [B]) wurden durch aufeinanderfolgende oxidative Manipulationen am borgebundenen Kohlenstoffzentrum (grün im Schema) synthetisiert. Chemoselektive Reaktionen dieser acylierten Organoborbausteine führten zu einer Reihe multifunktionalisierter Borderivate und ermöglichten Zugang wertvollen borylierten Heterocyclen (siehe Schema). Detailed facts of importance to specialist readers are published as "Supporting...
Abstract Described herein is the preparation of oxalyl boronate building blocks and their application for construction heterocycles. The unit, readily accessible through commercially available starting materials, enables a modular approach synthesis imidazoles. A variety aromatic, heteroaromatic, alkyl carboxaldehydes were condensed with boronates to afford substituted boryl imidazoles in regiocontrolled fashion. Subsequent palladium‐catalyzed cross‐coupling haloarenes furnished desired...
Fragment-based drug discovery (FBDD) has become an established method for the identification of efficient starting points programs. In recent years, electrophilic fragment screening garnered increased attention from both academia and industry to identify novel covalent hits tool compound or development against challenging targets. Herein, we describe design characterization acrylamide-focused library campaign extracellular signal-regulated kinase 2 (ERK2) using high-throughput protein...
We describe chemistry that allows synthesis and evaluation of borofragments <italic>via</italic> conjugation boron warheads with heterocycles biological significance.
Herein, we describe the rhodium-catalyzed C-H amination reaction of 1,2-boryl sulfamate esters derived from amphoteric α-boryl aldehydes. Depending on substitution pattern boryl ester, a diverse range five- or six-membered ring heterocycles are accessible using this transformation. The highly chemoselective nature functionalization preserves alkyl boronate functional group, which enables synthesis B-C-N and B-C-C-N motifs that present in number hydrolase inhibitors.
Abstract Herein, we demonstrate the use of α‐boryl aldehydes and acyl boronates in synthesis aminoboronic acid derivatives. This work highlights untapped potential boron‐substituted iminium ions offers insights into behavior N ‐methyliminodiacetyl (MIDA) during condensation tautomerization processes. The preparative value this contribution lies demonstration that various amines, including linear cyclic peptides, can be readily conjugated with boron‐containing fragments. A mild deprotection...
β-Glucocerebrosidase (GBA/GCase) mutations leading to misfolded protein cause Gaucher's disease and are a major genetic risk factor for Parkinson's dementia with Lewy bodies. The identification of small molecule pharmacological chaperones that can stabilize the increase delivery degradation-prone mutant GCase lysosome is strategy under active investigation. Here, we describe first use fragment-based drug discovery (FBDD) identify GCase. fragment hits were identified by using X-ray...
Herein we report the development of an α-allylation reaction α-boryl aldehydes that preserves carbon–boron bond under Pd0/PdII catalysis. A variety and allylic alcohols participate in this chemoselective transformation. The α-allylated products were obtained as single regioisomers.
The factors determining diastereoselectivity observed in the multicomponent conversion of amino acids, aziridine aldehyde dimers, and isocyanides into chiral piperazinones have been investigated. Amino acid-dependent selectivity for either trans- or cis-substituted piperazinone products has achieved. An experimentally determined model three-component reaction driven by dimers predictive value different substrate classes. Moreover, this is useful reconciling previously reported observations...
Genistein was efficiently synthesized from (2,4,6-trihydroxyphenyl)ethanone by a novel five-step procedure involving the formation of an enamino ketone, followed ring closure and Suzuki coupling reaction using palladium acetate poly(ethylene glycol).