Institut des Sciences Moléculaires de Marseille

Electronic and steric ligand effects both play major roles in organometallic chemistry and consequently in metal-mediated catalysis. Quantifying such parameters is of interest to better understand not only the parameters governing catalyst performance but also reaction mechanisms. Nowadays, ligand molecular architectures are becoming significantly more elaborate and existing models describing ligand sterics prove lacking. This review presents the development of a more general method to determine the steric parameter of organometallic ligands. Two case studies are presented: the tertiary phosphines and the N-heterocyclic carbenes.

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTStereocontrolled Domino ReactionsHélène Pellissier*View Author Information Aix-Marseille Université, UMR CNRS 7313 Institut des Sciences Moléculaires de Marseille Equipe Chirosciences, Case 561, Campus Saint Jérôme Avenue Esc. Normandie-Niemen, 13397 Marseille Cedex 20, France*Tel.: +33 4 91 28 27 65. E-mail: [email protected]Cite this: Chem. Rev. 2013, 113, 1, 442–524Publication Date (Web):November 16, 2012Publication History Received5 July 2012Published online16 November 2012Published inissue 9 January 2013https://pubs.acs.org/doi/10.1021/cr300271khttps://doi.org/10.1021/cr300271kreview-articleACS PublicationsCopyright © 2012 American Chemical SocietyRequest reuse permissionsArticle Views13508Altmetric-Citations606LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Addition reactions,Aldehydes,Chemical reactions,Multicomponent reactions,Stereoselectivity Get e-Alerts

Abstract While tremendous advances have been made in asymmetric synthesis, the resolution of racemates is still the most important industrial approach to the synthesis of chiral compounds. The use of enzymes for the kinetic resolution (KR) of racemic substrates to afford enantiopure compounds in high enantioselectivity and good yield has long been a popular strategy in synthesis. However, transition metal‐mediated and more recently organocatalyzed KRs have gained popularity within the synthetic community over the last two decades due to the progress made in the development of chiral catalysts for asymmetric reactions. Many catalytic non‐enzymatic procedures have been developed providing high enantioselectivity and yield for both products and recovered starting materials. Indeed, the non‐enzymatic KR of racemic compounds based on the use of a chiral catalyst is presently an area of great importance in asymmetric organic synthesis. The goal of this review is to provide an update on the principal developments of catalytic non‐enzymatic KR covering the literature since 2004. This review is subdivided into seven sections, according to the different types of compounds that have been resolved through catalytic non‐enzymatic KR, such as alcohols, epoxides, amines, alkenes, carbonyl derivatives, sulfur compounds and ferrocenes. Abbreviations: Ac: acetyl; acac: acetylacetone; AQN: anthraquinone; Ar: aryl; Atm: atmosphere; BINAM: 1,1′‐binaphthalenyl‐2,2′‐diamine; BINAP: 2,2′‐bis(diphenylphosphanyl)‐1,1′‐binaphthyl; BINEPINE: phenylbinaphthophosphepine; BINOL: 1,1′‐bi‐2‐naphthol; Bmim: 1‐butyl‐3‐methylimidazolium; Bn: benzyl; Boc: tert ‐butoxycarbonyl; Box: bisoxazoline; BSA: bis(trimethylsilyl)acetamide; Bu: butyl; Bz: benzoyl; c: cyclo; CBS: Corey–Bakshi–Shibata; Cbz: benzyloxycarbonyl; COD: cyclooctadiene; COE: cyclooctene; Cy: cyclohexyl; Dba: ( E,E )‐dibenzylideneacetone; DBU: 1,8‐diazabicyclo[5.4.0]undec‐7‐ene; DCC: N,N′ ‐dicyclohexylcarbodiimide; de : diastereomeric excess; DEAD: diethyl azodicarboxylate; Dec: decanyl; DHQD: dihydroquinidine; Difluorphos: 5,5′‐bis(diphenylphosphino)‐2,2,2′,2′‐tetrafluoro‐4,4′‐bi‐1,3‐benzodioxole; DIPEA: diisopropylethylamine: DKR: dynamic kinetic resolution; DMAP: 4‐dimethylaminopyridine; DMSO: dimethyl sulfoxide; DNA: deoxyribonucleic acid; DOSP: N ‐(dodecylbenzenesulfonyl)prolinate; DTBM: di‐ tert ‐butylmethoxy; ee : enantiomeric excess; Et: ethyl; equiv.: equivalent; Fu: furyl; Hex: hexyl; HIV: human immunodeficiency virus; HMDS: hexamethyldisilazide; KR: kinetic resolution; L: ligand; LDA: lithium diisopropylamide; MAO: methylaluminoxane; Me: methyl; Ms: mesyl; MTBE: methyl tert ‐butyl ether; Naph: naphthyl; nbd: norbornadiene; NBS: N ‐bromosuccinimide; NIS: N ‐iodosuccinimide; Pent: pentyl; Ph: phenyl; Piv: pivaloyl; PMB: p ‐methoxybenzoyl; Pr: propyl Py: pyridyl; r.t.: room temperature; s : selectivity factor; Segphos: 5,5′‐bis(diphenylphosphino)‐4,4′‐bi‐1,3‐benzodioxole; ( S,S′,R,R′) ‐Tangphos: (1S,1 S′ ,2 R ,2 R′ )‐1,1′‐di‐ tert ‐butyl‐(2,2′)‐diphospholane; TBS: tert ‐butyldimethylsilyl; TBDPS: tert ‐butyldiphenylsilyl; TCCA: trichloroisocyanuric acid ; TEA: triethylamine; TEMPO: tetramethylpentahydropyridine oxide; THF: tetrahydrofuran; Thio: thiophene; Tf: trifluoromethanesulfonyl; TMS: trimethylsilyl; Tol: tolyl; Ts: 4‐toluenesulfonyl (tosyl)

Cells have evolved multiple mechanisms to apprehend and adapt finely to their environment. Here we report a new cellular ability, which we term "curvotaxis" that enables the cells to respond to cell-scale curvature variations, a ubiquitous trait of cellular biotopes. We develop ultra-smooth sinusoidal surfaces presenting modulations of curvature in all directions, and monitor cell behavior on these topographic landscapes. We show that adherent cells avoid convex regions during their migration and position themselves in concave valleys. Live imaging combined with functional analysis shows that curvotaxis relies on a dynamic interplay between the nucleus and the cytoskeleton-the nucleus acting as a mechanical sensor that leads the migrating cell toward concave curvatures. Further analyses show that substratum curvature affects focal adhesions organization and dynamics, nuclear shape, and gene expression. Altogether, this work identifies curvotaxis as a new cellular guiding mechanism and promotes cell-scale curvature as an essential physical cue.

Pseudomonas aeruginosa regulates the production of many exoproteins and secondary metabolites via a hierarchical quorum-sensing cascade through LasR and RhlR and their cognate signal molecules N-(3-oxododecanoyl)-L-homoserine lactone (3O-C12-HSL) and N-(butanoyl)-L-homoserine lactone (C4-HSL). In this study, we found that transcription of the quorum sensing-regulated genes lecA (coding for PA-IL lectin), lasB (coding for elastase), and rpoS appeared to be growth phase dependent and their expression could not be advanced to the logarithmic phase in cells growing in batch culture by the addition of exogenous C4-HSL and 3O-C12-HSL. To identify novel regulators responsible for this growth phase dependency, a P. aeruginosa lecA::lux reporter strain was subjected to random transposon mutagenesis. A number of mutants affected in lecA expression were found that exhibited altered production of multiple quorum sensing-dependent phenotypes. While some mutations were mapped to new loci such as clpA and mvaT and a putative efflux system, a number of mutations were also mapped to known regulators such as lasR, rhlR, and rpoS. MvaT was identified as a novel global regulator of virulence gene expression, as a mutation in mvaT resulted in enhanced lecA expression and pyocyanin production. This mutant also showed altered swarming ability and production of the LasB and LasA proteases, 3O-C12-HSL, and C4-HSL. Furthermore, addition of exogenous 3O-C12-HSL and C4-HSL to the mvaT mutant significantly advanced lecA expression, suggesting that MvaT is involved in the growth phase-dependent regulation of the lecA gene.

Organo-click reaction: A new and complementary method to Huisgen's metal-catalyzed triazole synthesis is described using unactivated ketones and arylazides as the substrates and proline as an organocatalyst. Dramatic acceleration was observed for this reaction using microwave activation and high regio- and chemoselectivities were obtained for a wide range of ketones and arylazides (see scheme). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Over the past decade, ruthenium-mediated metathesis transformations, including polymerization reactions, cross-metathesis, ring-closing metathesis, enyne metathesis, ring-rearrangement metathesis, and also tandem processes, represent one of the most studied families of organic reactions. This has translated into the development of a large number of structurally diverse catalysts. Whereas most of these investigations are focused on determining catalytic performance, only rare examples of studies dealing with chemoselectivity have been reported to date. Usually, variations are observed in product conversions but rarely in product distributions. In this critical review, we provide an overview of the stereochemistry of newly formed C=C bonds either in ring-closing or cross-metathesis as a function of the catalyst structure. A discussion of disparities encountered in macrocyclisation reactions leading (or not) to the formation of dimeric products is also presented. Since distinctive metathesis products could be isolated as a function of the ligand borne by the ruthenium centre--phosphine or N-heterocyclic carbene in the dissymetrization of trienes, enyne metathesis and ring rearrangements, these topics are also discussed (72 references).

The design of highly emissive and stable blue emitters for organic light emitting diodes (OLEDs) is still a challenge, justifying the intense research activity of the scientific community in this field. Recently, a great deal of interest has been devoted to the elaboration of emitters exhibiting a thermally activated delayed fluorescence (TADF). By a specific molecular design consisting into a minimal overlap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) due to a spatial separation of the electron-donating and the electron-releasing parts, luminescent materials exhibiting small S 1 –T 1 energy splitting could be obtained, enabling to thermally upconvert the electrons from the triplet to the singlet excited states by reverse intersystem crossing (RISC). By harvesting both singlet and triplet excitons for light emission, OLEDs competing and sometimes overcoming the performance of phosphorescence-based OLEDs could be fabricated, justifying the interest for this new family of materials massively popularized by Chihaya Adachi since 2012. In this review, we proposed to focus on the recent advances in the molecular design of blue TADF emitters for OLEDs during the last few years.

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A CPL intensity of up to 3 × 10⁻² is achieved in π-extended 6-helicene derivatives, owing to an intense helicene-mediated exciton coupling. Corresponding top-emission CP-OLEDs afforded a promising <italic>g</italic>_El of around 8 × 10⁻³.

Abstract Since the first definition of domino reactions by Tietze in 1993, an explosive number of these fascinating reactions has been developed, allowing the easily building of complex chiral molecular architectures from simple materials to be achieved in a single step. Even more interesting, the possibility to join two or more reactions in one asymmetric domino process catalyzed by chiral metal catalysts has rapidly become one challenging goal for chemists, due to economical advantages, such as avoiding costly protecting groups and time‐consuming purification procedures after each step. The explosive development of enantioselective metal‐catalyzed domino including multicomponent reactions is a consequence of the considerable impact of the advent of asymmetric transition metal catalysis. This review aims to update the last developments of enantioselective one‐, two‐ and multicomponent domino reactions mediated by chiral metal catalysts, covering the literature since the beginning of 2006. Abbreviations: Ac: acetyl; AQN: anthraquinone; Ar: aryl; bdpp: 2,4‐bis(diphenylphosphino)pentane; BINAP: 2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl; BINEPINE: phenylbinaphthophosphepine; BINIM: binapthyldiimine; BINOL: 1,1′‐bi‐2‐naphthol; BIPHEP: 2,2′‐bis(diphenylphosphino)‐1,1′‐biphenyl; Bn: benzyl; Boc: tert ‐butoxycarbonyl; Box: bisoxazoline; BOXAX: 2,2′‐bis(oxazolyl)‐1,1′‐binaphthyl; BPTV: N‐benzene‐fused phthaloyl‐valine; Bu: butyl; Bz: benzoyl; Cat: catechol; Chiraphos: 2,3‐bis(diphenylphosphine)butane; cod: cyclooctadiene; Cy: cyclohexyl; DABCO: 1,4‐diazabicyclo[2.2.2]octane; dba: ( E,E )‐dibenzylideneacetone; DBU: 1,8‐diazabicyclo[5.4.0]undec‐7‐ene; DCE: dichloroethane; de : diastereomeric excess; DHQ: hydroquinine; DHQD: dihydroquinidine; DIFLUORPHOS: 5,5′‐bis(diphenylphosphino)‐2,2,2′,2′‐tetrafluoro‐4,4′‐bi‐1,3‐benzodioxole; DIPEA: diisopropylethylamine; DMF: dimethylformamide; DMSO: dimethyl sulfoxide; DOSP: N ‐ p ‐dodecylbenzenesulfonylprolinate; DPEN: 1,2‐diphenylethylenediamine; dtb: di‐ tert ‐butyl; dtbm: di‐ tert ‐butylmethoxy; E: electrophile; ee : enantiomeric excess; Et: ethyl; FBIP: ferrocene bis‐imidazoline bis‐palladacycle; Fc: ferrocenyl; FOXAP: ferrocenyloxazolinylphosphine; Hex: hexyl; HFIP: hexafluoroisopropyl alcohol; HMPA: hexamethylphosphoramide; i Pr‐DuPhos: 1,2‐bis(2,5‐diisopropylphospholano)benzene; Josiphos: 1‐[2‐(diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphine ethanol adduct; L: ligand; MCPBA: 3‐chloroperoxybenzoic acid; Me: methyl; Me‐DuPhos: 1,2‐bis(2,5‐dimethylphospholano)benzene; MEDAM: bis(dimethylanisyl)methyl; MOM: methoxymethyl; Naph: naphthyl; NMI: N ‐methylimidazole; MWI: microwave irradiation; Norphos: 2,3‐bis(diphenylphosphino)‐bicyclo[2.2.1]hept‐5‐ene; Ns: nosyl (4‐nitrobenzene sulfonyl); Nu: nucleophile; Oct: octyl; Pent: pentyl; Ph: phenyl; PHAL: 1,4‐phthalazinediyl; Pin: pinacolato; PINAP: 4‐[2‐(diphenylphosphino)‐1‐naphthalenyl]‐ N ‐[1‐phenylethyl]‐1‐phthalazinamine; Pr: propyl; Py: pyridyl; PYBOX: 2,6‐bis(2‐oxazolyl)pyridine; QUINAP: 1‐(2‐diphenylphosphino‐1‐naphthyl)isoquinoline; QUOX: quinoline‐oxazoline; Segphos: 5,5′‐bis(diphenylphosphino)‐4,4′‐bi‐1,3‐benzodioxole; Solphos: 7,7′‐bis(diphenylphosphino)‐3,3′,4,4′‐tetrahydro‐4,4′‐dimethyl‐8,8′‐bis‐2 H ‐1,4‐benzoxazine; SPRIX: spirobis(isoxazoline); SYNPHOS: 6,6′‐bis(diphenylphosphino)‐2,2′,3,3′‐tetrahydro‐5,5′‐bi‐1,4‐benzodioxin; Taniaphos: [2‐diphenylphosphinoferrocenyl]( N , N ‐dimethylamino)(2‐diphenylphosphinophenyl)methane; TBS: tert ‐butyldimethylsilyl; TC: thiophene carboxylate; TCPTTL: N ‐tetrachlorophthaloyl‐ tert ‐leucinate; TEA: triethylamine; Tf: trifluoromethanesulfonyl; TFA: trifluoroacetic acid; THF: tetrahydrofuran; TMS: trimethylsilyl; Tol: tolyl; Ts: 4‐toluenesulfonyl (tosyl); C 3 ‐Tunephos: 1,13‐bis(diphenylphosphino)‐7,8‐dihydro‐6 H ‐dibenzo[ f,h ][1,5]dioxonin; VAPOL: 2,2′‐diphenyl‐[3,3′‐biphenanthrene]‐4,4′‐diol

Mitochondrial respiration (oxidative phosphorylation, OXPHOS) is an emerging target in currently refractory cancers such as pancreatic ductal adenocarcinoma (PDAC). However, the variability of energetic metabolic adaptations between PDAC patients has not been assessed in functional investigations. In this work, we demonstrate that OXPHOS rates are highly heterogeneous between patient tumors, and that high OXPHOS tumors are enriched in mitochondrial respiratory complex I at protein and mRNA levels. Therefore, we treated PDAC cells with phenformin (complex I inhibitor) in combination with standard chemotherapy (gemcitabine), showing that this treatment is synergistic specifically in high OXPHOS cells. Furthermore, phenformin cooperates with gemcitabine in high OXPHOS tumors in two orthotopic mouse models (xenografts and syngeneic allografts). In conclusion, this work proposes a strategy to identify PDAC patients likely to respond to the targeting of mitochondrial energetic metabolism in combination with chemotherapy, and that phenformin should be clinically tested in appropriate PDAC patient subpopulations.

Three is a lucky number: An enantioselective transformation of allylic alcohols into β-chiral saturated alcohols has been developed by combining two distinct metal- and organocatalyzed catalytic cycles. This waste-free triple cascade process merges an iron-catalyzed borrowing-hydrogen step with an aminocatalyzed nucleophilic addition reaction.

Molecular and macromolecular chiral π-conjugated diketopyrrolopyrrole (DPP)-helicene derivatives were prepared and their chiroptical properties examined experimentally and theoretically. Exciton coupling leads to red and near-infrared circularly polarized absorption and luminescence arising from the achiral DPP units in the helical environment, highlighting an interesting synergy between the chiral helicene and the organic dye.

Various cultivars of Perilla frutescens (L.) (var. crispa and var. frutescens) Britt. were harvested in China and Japan. They were easily differentiated on the basis of their foliage color, that varied from red to green. Water extracts of dried plants were investigated for their antioxidant activity (AA) and their polyphenolic compounds compared. Among them, cinnamic acid derivatives (coumaroyl tartaric acid, caffeic acid and rosmarinic acid), flavonoids (apigenin 7-O-caffeoylglucoside, scutellarein 7-O-diglucuronide, luteolin 7-O-diglucuronide, apigenin 7-O-diglucuronide, luteolin 7-O-glucuronide, and scutellarein 7-O-glucuronide) and anthocyanins (mainly cis-shisonin, shisonin, malonylshisonin and cyanidin 3-O-(E)-caffeoylglucoside-5-O-malonylglucoside) were quantified. AA assays are based on the inhibition of the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). The DPPH radical scavenging activity was calculated as Trolox [(+/-)-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid] equivalent antioxidant capacity (TEAC). The mean amount of total phenolics of the water extracts (4-29 micromol/100 mL) and the TEAC value calculated (23-167 micromol TE/100 mL) confirmed the high antioxidant activity of these leaf water extracts. These results were highly correlated within some o-dihydroxylated polyphenolic compounds and AA.

p53 exerts its tumor suppressor function mainly through transcriptional induction of target genes involved in several processes, including cell cycle checkpoints, apoptosis, and regulation of cell redox status. p53 antioxidant function is dependent on its transcriptional activity and proceeds by sequential induction of antioxidant and proapoptotic targets. However, none of the thus far renowned p53 targets have proved able to abolish on their own the intracellular reactive oxygen species (ROS) accumulation caused by p53 deficiency, therefore pointing to the existence of other prominent and yet unknown p53 antioxidant targets. Here, we show that TP53INP1 represents such a target. Indeed, TP53INP1 transcript induction on oxidative stress is strictly dependent on p53. Mouse embryonic fibroblasts (MEF) and splenocytes derived from TP53INP1-deficient (inp1(-/-)) mice accumulate intracellular ROS, whereas overexpression of TP53INP1 in p53-deficient MEFs rescues ROS levels to those of p53-proficient cells, indicating that TP53INP1 antioxidant function is p53 independent. Furthermore, accumulation of ROS in inp1(-/-) cells on oxidant challenge is associated with decreased expression of p53 targets p21/Cdkn1a, Sesn2, TAp73, Puma, and Bax. Mutation of p53 Ser(58) (equivalent to human p53 Ser(46)) abrogates transcription of these genes, indicating that TP53INP1-mediated p53 Ser(58) phosphorylation is implicated in this process. In addition, TP53INP1 deficiency results in an antioxidant (N-acetylcysteine)-sensitive acceleration of cell proliferation. Finally, TP53INP1 deficiency increases oxidative stress-related lymphoma incidence and decreases survival of p53(+/-) mice. In conclusion, our data show that TP53INP1 is a major actor of p53-driven oxidative stress response that possesses both a p53-independent intracellular ROS regulatory function and a p53-dependent transcription regulatory function.

ABSTRACT Since the 1970s, increase in fire frequency has been observed in all European Mediterranean regions. The objectives of this study were (1) to determine the effects of wildfire frequency on the recovery at short‐ and long‐term of soil chemical and microbial properties and (2) to identify the mechanisms underlying the recovery of these sites properties. Soils from 17 plots (Maures mountains range, Var, France) were classified into 5 wildfire regimes (i.e. not burned since at least 57 years ago, infrequently and frequently burned‐with time since fire between 4 and 17 years). Soil samples from these plots were analysed for their nutrient content, chemical functions of soil organic matter (SOM) using FT‐MIR spectroscopy and microbial mineralising activities. Our results showed that the frequent wildfire regime slowed down the recovery in the short term of SOM spectroscopic properties and nutrient availability. Both low quantity and low quality (i.e. high percentage of aromatic and phenolic organic forms) of soil organic matter were found to be related to soil microbial recovery at 4 years after frequent wildfires. The frequent wildfires improved the recovery in net nitrification and nitrate content, leading to an increase in catabolic evenness and a recovery in microbial C‐substrate utilisation profiles between 4 and 17 years. However, frequent wildfires slowed down the recovery of hydrolytic enzyme pool (i.e. FDA hydrolases) and phenol oxidase activity, both involved in soil C cycling. Overall, our observations suggest that 4 fires in 50 years is a threshold beyond which soil quality may be endangered. Copyright © 2011 John Wiley &amp; Sons, Ltd.

The copper-catalyzed conjugate addition of Grignard reagents to 3-substituted cyclic enones allows the formation of all-carbon chiral quaternary centers. We demonstrate in this article that N-heterocyclic carbenes act as efficient chiral ligands for this transformation. High enantioselectivities (up to 96% ee) could be obtained for a variety of substrates.

During the past decades, the development of emissive materials for organic light-emitting diodes (OLEDs) in infrared region has focused the interest of numerous research groups as these devices can find interest in applications ranging from optical communication to defense. To date, metal complexes have been most widely studied to elaborate near-infrared (NIR) emitters due to their low energy emissive triplet states and their facile access. In this review, an overview of the different metal complexes used in OLEDs and enabling to get an infrared emission is provided.

Polycyclic structures fused at a central carbon are of great interest due to their appealing conformational features and their structural implications in biological systems. Although progress in the development of synthetic methodologies towards such structures has been impressive, the stereoselective construction of such quaternary stereocentres remains a significant challenge in the total synthesis of natural products. This review highlights the progress in the formation of 1-oxaspiro[4.n]alkan-2-ones (2≤n≤7) with concomitant formation of the quaternary spiro centre.