Cyrille Sabot

Université de Rouen Normandie | UR · Département de Chimie

We showcase the successful combination of photochemistry and kinetic target‐guided synthesis (KTGS) for rapidly pinpointing enzyme inhibitors. KTGS is a fragment‐based drug discovery (FBDD) methodology in which the biological target (BT) orchestrates the construction of its own ligand from fragments featuring complementary reactive functionalities....

Coumarins still remain one of the most widely explored fluorescent dyes, with a broad spectrum of applications spanning various fields, such as molecular imaging, bioorganic chemistry, materials chemistry, or medical sciences. Their fluorescence is strongly based on a push‐pull mechanism involving an electron‐donating group (EDG), mainly located at...

We showcase the successful combination of photochemistry and kinetic target‐guided synthesis (KTGS) for rapidly pinpointing enzyme inhibitors. KTGS is a fragment‐based drug discovery (FBDD) methodology in which the biological target (BT) orchestrates the construction of its own ligand from fragments featuring complementary reactive functionalities....

Cross-linking mass spectrometry (XL-MS) has become a very useful tool for studying protein complexes and interactions in living systems. It enables the investigation of many large and dynamic assemblies in their native state, providing an unbiased view of their protein interactions and restraints for integrative modeling. More researchers are turni...

Cross-linking Mass Spectrometry (XL-MS) has become a very useful tool for studying protein complexes and interactions in living systems. It enables the investigation of many large and dynamic assemblies in their native state, providing an unbiased view of their protein interactions, and restraints for integrative modeling. More researchers are turn...

Glycan metabolic engineering is a powerful tool for studying the glycosylation in living plant cells. The use of modified monosaccharides such as deoxy or fluorine-containing glycosides has been reported as a powerful pharmacological approach for studying the carbohydrate metabolism. 1,3,4-tri-O-acetyl-2-fluoro-l-fucose (2F-Fuc) is a potent inhibit...

Photophysical properties of quinoxalin‐2(1H)‐ones have long been neglected, in particular compared with those of coumarins, their oxygenated counterparts, despite their complementarity in terms of absorbance and fluorescence windows. This review provides first an overview of the synthesis of quinoxalin‐2(1H)‐ones, focusing on the most recent contri...

Proteins are able to irreversibly assemble biologically active ligands from building blocks bearing complementary reactive functions due their spatial proximity, through a kinetic target‐guided synthetic process (also named in situ click chemistry). Although linkages thus formed are mostly passive, some of them have shown to significantly contribut...

The selective functionalization of biomolecules such as proteins, nucleic acids, lipids or carbohydrates is a focus of persistent interest due to their widespread use, ranging from basic chemical biology research to gain insight into biological processes to the most promising biomedical applications, including the development of diagnostics or targ...

Broad scope one‐pot diazirine synthesis strategies have been developed using two different oxidants depending on the nature of the starting material. In all cases, an inexpensive commercial solution of ammonia (NH3) in methanol (MeOH) was employed, avoiding the difficult use of liquid ammonia. With aliphatic ketones, t‐butyl hypochlorite (t‐BuOCl)...

Described herein is a compact benzophenone-quinoxalinone photoaffintiy labelling hybrid system with caged fluorescence properties. Upon visible blue LED irradiation (λmax 450 nm), this photo-crosslinker is able to covalently capture proteins...

Kinetic target-guided synthesis (KTGS) is a promising tool for the discovery of biologically active compounds. It relies on the identification of potent ligands that are covalently assembled by the biological targets themselves from a pool of reagents. Significant effort is devoted to developing new KTGS strategies; however, only a handful of bioco...

Phenols are well-known precursors of cyclohexadienones, which have widespread applications in organic synthesis. In contrast, their hydroxypyridine counterparts have not been explored yet. An unprecedented oxidative dearomatization of a 3-hydroxypyridine involving an unexpected deformylation step is reported. The chemical reactivity of the resultin...

The copper-catalyzed alkyne-azide cycloaddition (CuAAC) is one of the most powerful chemical strategies for selective fluorescent labeling of biomolecules in in vitro or biological systems. In order to accelerate the ligation process and ensure efficient formation of conjugates under diluted conditions, external copper(I) ligands or sophisticated c...

A brief literature survey reveals that metal-free ligation such as the maleimide-based cycloaddition with electron-rich (hetero)dienes is a widespread tool for the assembly of (bio)molecular systems with applications in biotechnology, materials science, polymers and bio-organic chemistry. Despite their everyday use, only scattered data about their...

The fluorescein isothiocyanate FITC is one of the most extensively used fluorescent probe for the labelling of biomolecules. The isothiocyanate function reacts with lysine residues of proteins to provide a chemically stable thiourea linkage without releasing any by-product. However, diversification of isothiocyanate-based reagents is still hampered...

Chemoselective, biocompatible ligation reactions are the key components for efficient and modular access to biomolecular scaffolds. Tetrazine ligation leads to the formation of a mixture of isomers, which results in...

Non‐protein thiols such as GSH, Hcy, or Cys, are present at different concentration levels in the body depending on the thiol species and their localization (plasma, cell, urine etc…). They play vital roles in controlling redox‐mediated biological processes, and abnormal levels of biothiols are related to a variety of syndromes. In few years, fluor...

Since their first use in bioconjugation more than 50 years ago, maleimides have become privileged chemical partners for the site selective modification of proteins through thio-Michael addition of biothiols and, to a lesser extent, via Diels‒Alder (DA) reactions in combination with biocompatible dienes. Prominent examples include immunotoxins and m...

Correction for ‘Metal-free oxidative ring contraction of benzodiazepinones: an entry to quinoxalinones’ by Hasan Mtiraoui, et al. , Org. Biomol. Chem. , 2017, 15 , 3060–3068.

Quinoxalinones are widely exploited for their biological activities, but more rarely for their fluorescence behavior, partly due to a lack of data. Herein, we investigated the photophysical properties of selected 3-benzoylquinoxalin-2-ones and their NaBH4-reduced products, obtained by the rearrangement of benzodiazepin-2-ones. To illustrate their p...

The first synthesis of the proposed structures of chaetoviridins A 1–4 has been achieved in 10 steps by controlling the syn- or anti-aldol side chain. The angular lactone has been regioselectively introduced by condensation of a chiral dioxin-4-one to cazisochromene. Comparison of the NMR and circular dichroism data of the synthesized and reported...

A novel and practical synthesis of 3-benzoylquinoxalin-2(1H)-ones from benzodiazepin-2-ones in two steps from commercially available starting materials is reported. The reaction was achieved in the presence of N-bromosuccinimide in DMSO which served both as a solvent and an oxidant. Significantly, the yet unknown ketone to alcohol fluorescence turn...

A series of novel O-triazolyl-1,5-benzodiazepin-2-ones 6a–o and O-isoxazolyl-1,5-benzodiazepin-2-ones 7a–o was synthesized via a Cu(I)-catalyzed 1,3-dipolar alkyne–azide coupling reaction of N-substituted-1,5-benzodiazepine–alkyne derivatives 3a–c with various aromatic azides 4a–e and nitrile oxides 5a–e, respectively. The chemical structures of sy...

Fluorogenic reactions are largely underrepresented in the toolbox of chemoselective ligations despite their tremendous potential, particularly in chemical biology and biochemistry. In this respect, we have investigated in full detail the fluorescence behaviour of the azaphthalamide, a scaffold which is generated through a hetero-Diels–Alder reactio...

A new family of fluorescent 1,5-benzodiazepin-2-one (HBD) borate complexes was prepared in good yields, and fully characterized by means of MS, NMR and IR spectroscopy, as well as X-ray crystal structure analysis for compound 13. Unlike their uncomplexed congeners, most of these cyclic boranils were emissive both in solution and the solid state, wi...

Fluorescent coumarins are an important class of small-molecule organic fluorophores ubiquitous in different well-established and emerging fields of research including, among others, biochemistry and chemical biology. The present work aims at covering the poor detectability of coumarin-based conjugates by mass spectrometry while keeping important ph...

Photoluminescent materials, that are now ubiquitous in our everyday life, have particularly attracted the attention of the scientific community these last few years due to potential important applications such as in bio-imaging, sensing or optoelectronics. In this context, relatively few different families of molecules have been reported to exhibit...

The 5-alkoxyoxazole ring system has proved to be a useful and versatile building block that is involved in a variety of chemical transformations (e.g., hetero-Diels–Alder reactions, formal 1,3-dipolar cycloadditions, photochemical [2+2] cycloadditions, Claisen rearrangements, and ring-opening processes). 5-Alkoxyoxazoles have provided synthetic acc...

Since the recent discovery that hydrogen sulfide plays a key role in many biological and physiological processes, the development of novel methods to efficiently detect this molecule has become an intensive field of research. In this context, fluorimetric strategies have become one of the methods of choice. However, very few different reducible che...

The kinetic target-guided synthesis (KTGS) strategy is an unconventional approach to lead discovery that takes advantage of the presence of the biological target itself in order to irreversibly assemble the best inhibitors from an array of building blocks. This strategy has grown over the last two decades notably after the introduction of the in si...

Diversification of existing chemoselective ligations is required to efficiently access complex and well-defined biomolecular assemblies with unique and valuable properties. The development and bioconjugation applications of a novel Diels-Alder-based irreversible site-specific ligation are reported. The strategy is based on a Kondrat'eva cycloadditi...

A complete experimental and theoretical study of the thermally-controlled metal-free decarboxylative hetero-Diels-Alder (HDA) reaction of 5-alkoxyoxazoles with acrylic acid is reported. This strategy offers a new entry to valuable 2,6-difunctionalized 3-hydroxypyridines from readily available 2- and 4-disubstituted 5-alkoxyoxazoles. The reaction co...

The irreversible Michael addition of thiols to acrylamides is reported as a new tool for the kinetic target-guided synthesis. In an unprecedented enzymatic hydrolysis/thio-Michael addition procedure, potent and selective acetylcholinesterase inhibitors are assembled by the enzyme using both its esterasic and templating ability.

A complete experimental and theoretical study of the thermally controlled metal-free decarboxylative hetero-Diels−Alder (HDA) reaction of 5- alkoxyoxazoles with acrylic acid is reported. This strategy offers a new entry to valuable 2,6-difunctionalized 3-hydroxypyridines from readily available 2- and 4- disubstituted 5-alkoxyoxazoles. The reaction...

The enzyme-directed synthesis is an emerging fragment-based lead discovery approach in which the biological target is able to assemble its own multidentate ligands from a pool of building blocks. Here, we report for the first time the use of the human acetylcholinesterase (AChE) as an enzyme for the design and synthesis of new potent heterodimeric...

The first synthesis and photophysical properties of a fluorecently-labeled camptothecin derivative namely camptothecin-FI (CPT-FI), an antitumoral agent that targets topoisomerase I, are reported. The preparation of this fluorescent conjugate is based on a highly convergent and flexible approach which enables the rapid chemical modification of the...

A modified Kondrat'eva cycloaddition involving an unprecedented thermally controlled metal-free decarboxylative aromatization affords an expedient access to natural 3-hydroxypyridine/piperidine systems.

A rapid and general access to diversely substituted 5-alkoxyoxazoles 2 (i.e., R(1), R(2) = alkyl, phenyl) from easily accessible α-triflyloxy/hydroxy esters 1 and nitriles with good yields (41-76%) is reported. The versatility of the cyclization is shown for a range of substrates with high selectivity toward triflates over mesylates and proved to b...

A general and single-step access to polysubstituted 3-hydroxypyridine scaffolds via hetero-Diels-Alder (HDA) reactions between readily prepared 5-ethoxyoxazoles and dienophiles is reported. The HDA reaction, run in the presence of Nd(OTf)(3) at room temperature, was successfully applied to various 5-ethoxyoxazoles showing good functional group tole...

An oxidative Prins-pinacol tandem process mediated by a hypervalent iodine reagent has been developed. This oxidative version of the famous tandem process fits within the concept of "aromatic ring umpolung" and allows the stereoselective transformation of simple phenols into highly elaborated spirocyclic dienone cores containing several quaternary...

A novel, convergent approach to the antitumor agent camptothecin has been developed with a rhodium (II)-catalyzed intramolecular [3+2] cycloaddition as the key step.

Center stage: An oxidative Prins-pinacol tandem process mediated by a hypervalent iodine reagent has been accomplished. The strategy allows rapid access to highly functionalized spirocyclic cores (see scheme) present in many natural products. A first application to the formal synthesis of (?)-platensimycin has been achieved.

The first total synthesis of (±)-17-norcamptothecin, a novel camptothecin analog possessing an α-hydroxy-γ-lactone E-ring, has been accomplished by using a short and flexible route. The stability of this new compound in aqueous medium has been evaluated through fluorescence spectroscopy.

Treatment of various substituted phenols in the presence of (diacetoxyiodo)benzene promotes the formation of a phenoxenium ion, a very electrophilic species able to react with various nucleophiles leading rapidly to a plethora of different cores present in natural products via several novel oxidative processes. This strategy fits within the concept...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Treatment of various dienimides in the presence of a Lewis acid and (trimethylsiloxy)furan leads to the corresponding aniline furan‐2(5 H )‐ones. The same treatment with furan yields a triaryl product and, surprisingly, a byproduct with a pentacyclo[5.4.0.0.0.0]undecane main core. The formation of this birdcage system containing nine stereogenic ce...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

An oxidative Wagner-Meerwein transposition involving different functionalities mediated by a hypervalent iodine reagent has been accomplished. The strategy fits within the concept of "aromatic ring umpolung" and allows rapid access to highly functionalized cores.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The expedient synthesis of a novel chiral (1S,2S)-N-[(2-isothiocyanato)cyclohexyl] trifluoromethanesulfonamide and its use as a derivatizing auxiliary for the straightforward determination of optical purity of chiral amines are reported.

A concise total synthesis of (+/-)-aspidospermidine has been achieved in twelve steps from inexpensive 4-ethylphenol, based on an oxidative Hosomi-Sakurai reaction via the concept of "aromatic ring umpolung".

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

An oxidative Friedel-Crafts reaction involving different aromatic compounds mediated by a hypervalent iodine reagent has been performed, using polysubstituted phenols. The strategy fits within the concept of "aromatic ring umpolung", which opens up novel opportunities in chemical synthesis. The reaction takes place in useful yields, and allows rapi...

Treatment of unfunctionalized acyclic ketoaldehydes with a catalytic amount of 1,5,7-triazabicyclo[4.4.0]dec-5-ene induces a direct intramolecular 5- and 6-enolexo aldolization, furnishing 2-ketocyclopentanols and 2-ketocyclohexanols in good-to-excellent yields. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

An oxidative allylation process mediated by a hypervalent iodine reagent has been performed on polysubstituted phenols. This reaction, occurring in useful to good yields, leads to a rapid access to dienones containing a quaternary carbon center.

Concise diastereoselective syntheses of the marine (+/-)-panacene and terrestrial (+/-)-desbromopanacene have been achieved in a few steps based on a concept of "aromatic ring umpolung". The synthetic avenue to the (+/-)-panacene involved a novel oxymercuration strategy to produce the correct configuration of the bromoallene moiety.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Treatment of various substituted phenols in the presence of iodobenzene diacetate, perfluorinated alcohols and furan, allylsilanes or cyclic enol ethers promotes an oxidative annulation process in moderate to useful yields. In only one step, this method produces different heterocyclic rings such as dihydrofuranobenzofurans, tetrahydrofuranobenzofur...

Treatment of unfunctionalized acyclic ketoaldehydes with a catalytic amount of 1,5,7-triazabicyclo[4.4.0]dec-5-ene induces a direct intramolecular 5- and 6-enolexo aldolization, furnishing 2-ketocyclopentanols and 2-ketocyclohexanols in good-to-excellent yields. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).

Treatment of various substituted phenols in the presence of allyltrimethylsilane, iodobenzene diacetate, and perfluorinated alcohol promotes oxidative formal [2+3] cycloaddition in moderate to useful yields.

Ionic liquids are remarkably suitable and clean media for performing nonenzymatic kinetic resolution (KR) of amines through enantioselective N-acetylation: high levels of selectivity were obtained with a large variety of amines at room temperature (up to s = 30).

We describe the first effective H/D exchange reaction with acidic substrates in CDCl(3) at room temperature. The particularly mild reaction conditions involved (solvent, base, and temperature) allow the chemoselective deuteration of ketones over esters. An NMR study was conducted with the aim of rationalizing the results obtained in the presence of...

Aminolysis of esters by using the organocatalyst 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) is reported. Secondary and tertiary amides were synthesized from alkyl or aryl esters with a variety of primary and secondary amines in good to excellent yields (60–94%) under solvent-free conditions (SFC).