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Search for "high throughput" in Full Text gives 97 result(s) in Beilstein Journal of Organic Chemistry.
Innovative synthesis of drug-like molecules using tetrazole as core building blocks
- Jingyao Li,
- Ajay L. Chandgude,
- Qiang Zheng and
- Alexander Dömling
Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85
- . During preclinical research large screening libraries are integral part of the structure-based drug design and high-throughput screening and facile, efficient synthetic methods to explore diverse chemical spaces are of great help [2][3][4]. However, due to the vastness of chemical space, generation of
Graphical Abstract
Figure 1: Tetrazole drugs, current assembly strategies, and novel building block strategy.
Scheme 1: Synthesis of tetrazole building blocks. Isolated yields.
Scheme 2: Substrate scope of Passerini products 3. Isolated yields.
Scheme 3: Substrate scope of Ugi products 4 and 5. Isolated yields.
Scheme 4: Synthesis of tetrazole building block 6. Isolated yield.
Methodology for awakening the potential secondary metabolic capacity in actinomycetes
- Shun Saito and
- Midori A. Arai
Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69
- groups, using a ribosome engineering approach in Streptomyces sp. CB02009 (Figure 2d) [48]. Seyedsayamdost et al. developed the high-throughput elicitor screening (HiTES) approach, a forward chemical genetics method that identifies small-molecule inducers of silent natural products (Figure 2e) [49]. Han
Graphical Abstract
Figure 1: Schematic diagram of methods to activate silent genes in actinomycetes as presented in this review....
Figure 2: Structures of secondary metabolites obtained from actinomycetes using artificial methods.
Figure 3: Structures of secondary metabolites obtained from actinomycetes by adjusting culture conditions.
Figure 4: Structures of secondary metabolites obtained by high-temperature culture of actinomycetes.
Figure 5: Structures of secondary metabolites obtained by co-culture of actinomycetes with other microorganis...
Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization
- Senze Qiao,
- Zhongyu Cheng and
- Fuzhuo Li
Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66
- stability, etc. Emerging research methods on bioinformatics, computational modeling, deep learning, protein engineering, and high-throughput screening will accelerate the pace of enzyme discovery to provide a broader platform of tools for employing chemoenzymatic strategies [64][87][88][89]. More
Graphical Abstract
Scheme 1: Brief introduction of thioesterase (TE) domain. (a) NRPS and PKS assembly lines. (b) Mechanism of T...
Scheme 2: Chemoenzymatic synthesis of tyrocidine A and its analogs. (a) First-gen chemoenzymatic synthesis of...
Scheme 3: Representative examples of NAC-activated thioesters-mediated biocatalytic macrolactamization.
Scheme 4: Chemoenzymatic synthesis of CDA, daptomycin and their analogs. (a) Biocatalytic macrocyclization of...
Scheme 5: Chemoenzymatic synthesis of surugamide B and related natural products. (a) Three synthetic strategi...
Scheme 6: Chemoenzymatic synthesis of the pikromycins. (a) Macrocyclization of 10-deoxymethynolide catalyzed ...
Scheme 7: Chemoenzymatic synthesis of the juevnimicins.
Scheme 8: Chemoenzymatic synthesis of the cryptophycins.
Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin
- Jon Lundstrøm,
- Emilie Gillon,
- Valérie Chazalet,
- Nicole Kerekes,
- Antonio Di Maio,
- Ten Feizi,
- Yan Liu,
- Annabelle Varrot and
- Daniel Bojar
Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31
- realm of therapeutics, lectins such as mistletoe lectins have shown promise in cancer therapy, by virtue of their ability to induce apoptosis in malignant cells [7]. Further, the creation of lectin arrays [8][9], which employ a diverse set of characterized lectins, has enabled high-throughput glycan
Graphical Abstract
Figure 1: Characterizing a new lectin from the melon Cucumis melo. (a) Evolutionary relationships of common R...
Figure 2: Characterizing the binding specificity of CMA1. (a, b) Lectin produced in mammalian cells was analy...
Figure 3: Assessing and quantifying in-solution binding of CMA1. (a) Erythrocyte agglutination assay. Using r...
Figure 4: Structural insights into the binding mechanism of CMA1. (a, b) Overall representation of the N-term...
Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target
- Milandip Karak,
- Cian R. Cloonan,
- Brad R. Baker,
- Rachel V. K. Cochrane and
- Stephen A. Cochrane
Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22
- a more viable strategy in contrast to other methodologies, as it offers the potential to generate ample quantities of lipid II analogues suitable for high-throughput screening endeavors. In recent years, a major focus of the Cochrane lab has been the chemical synthesis of bacterial polyprenyls to
Graphical Abstract
Figure 1: Structure of lipid II, with variable positions shown in red and antimicrobial-binding motifs highli...
Figure 2: List of i) glycosyl donors and ii) glycosyl acceptors used in this study.
Scheme 1: Synthesis of disaccharide pentapeptide core 7.
Scheme 2: Synthesis of lipid II (11) and its analogues 8–10.
NMRium: Teaching nuclear magnetic resonance spectra interpretation in an online platform
- Luc Patiny,
- Hamed Musallam,
- Alejandro Bolaños,
- Michaël Zasso,
- Julien Wist,
- Metin Karayilan,
- Eva Ziegler,
- Johannes C. Liermann and
- Nils E. Schlörer
Beilstein J. Org. Chem. 2024, 20, 25–31, doi:10.3762/bjoc.20.4
- rapid and comparatively easy deduction of structural features with the only requirement being the molecule's solubility in deuterated solvents. Therefore, NMR spectroscopy is of ubiquitous presence in many disciplines today. At the same time, with the high throughput analysis of samples that has been a
Graphical Abstract
Figure 1: NMRium.org user interface showing a 2D NMR quiz for an unknown compound with a given molecular form...
Figure 2: NMRium interface assignment functionality for a drag-and-drop example.
Figure 3: Analysis of overlapping signals with the NMRium ranges editor.
GlAIcomics: a deep neural network classifier for spectroscopy-augmented mass spectrometric glycans data
- Thomas Barillot,
- Baptiste Schindler,
- Baptiste Moge,
- Elisa Fadda,
- Franck Lépine and
- Isabelle Compagnon
Beilstein J. Org. Chem. 2023, 19, 1825–1831, doi:10.3762/bjoc.19.134
- single spectrum is arbitrarily chosen by the operator and serves as reference for all future analyses. The latest MS–IR developments brought the data collection down to few seconds [5]. This is a considerable step towards high throughput carbohydrate analysis, which must be accompanied by fast data
Graphical Abstract
Figure 1: (a) Fingerprint of an unknown monosaccharide. (b) Labelled reference spectra of monosaccharide stan...
Figure 2: Typical experimental MS–IR spectra of the four categories of monosaccharides included in the first ...
Figure 3: Synthetic IRMPD spectrum (grey trace) generated on the basis of a high resolution endogeneous exper...
Figure 4: Model accuracy dependance with experimental conditions, represented by the dataset augmentation par...
Figure 5: DNN Prediction results for third endogenous dataset (5 hexosamine samples and 7 other molecules). T...
Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent
- Stéphanie Hesse
Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110
- classes of heterocyclic compounds studied for a long time. Those scaffolds have attracted great attention since the introduction of various glitazones and epalrestat into clinical use for the treatment of type-II diabetes (Figure 1). Indeed, those compounds are often identified as hits in high throughput
Graphical Abstract
Figure 1: Examples of rhodanines and related five-membered heterocycles with interesting biological activitie...
Scheme 1: Synthesis of 5-benzylidenerhodanine derivatives. Conditions: areaction performed for 3 h at 60 °C. b...
Photoredox catalysis harvesting multiple photon or electrochemical energies
- Mattia Lepori,
- Simon Schmid and
- Joshua P. Barham
Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81
- first efforts in this direction [32][33]. Finally, both techniques are amenable to large-scale synthesis and ideally integrated with state-of-the-art reactor technology platforms, such as continuous flow reactors and high throughput screening plates. Various examples of scalability will be highlighted
Graphical Abstract
Figure 1: Oxidative and reductive activations of organic compounds harvesting photoredox catalysis.
Figure 2: General catalytic cycles of radical ion conPET (left) and radical ion e-PRC (right).
Figure 3: “Beginner’s guide”: comparison between advantages, capacities, and prospectives of conPET and PEC.
Figure 4: A) conPET reductive dehalogenation of aryl halides with PDI. B) Reductive C–H arylation with pyrrol...
Figure 5: A) Chromoselective mono- and disubstitution or polybrominated pyrimidines with pyrroles. B) Sequent...
Figure 6: A) Synthesis of pyrrolo[1,2-a]quinolines. B) Synthesis of ullazines.
Figure 7: A) Reductive phosphorylation of aryl halides via conPET. B) Selected examples from the substrate sc...
Figure 8: A) Reductive dehalogenation of aryl halides via conPET and selected examples from the substrate sco...
Figure 9: A) Reductive C–H arylation of aryl halides via conPET (top) and selected examples from the substrat...
Figure 10: A) Reductive hydrodehalogenation of aryl halides with Mes-Acr-BF4. B) Selected examples from the su...
Figure 11: A) Reductive hydrodechlorination of aryl chlorides with 4-DPAIPN. B) Proposed formation of CO2•−. C...
Figure 12: A) Reductive conPET borylation with 3CzEPAIPN (top) and selected examples from the substrate scope ...
Figure 13: Scale-up of conPET phosphorylation with 3CzEPAIPN.
Figure 14: A) Borylation of 1d. B) Characteristics and structure of PC1 with green and red parts showing the l...
Figure 15: A) Reductive C–H arylation scope with polysulfide conPET (top) and selected examples from the subst...
Figure 16: Scale-up of A) C–H arylation and B) dehaloborylation with polysulfide photocatalysis in continuous-...
Figure 17: A) Formation of [Ir1]0 and [Ir2]0 upon PET between [Ir1]+ and Et3N. B) Mechanism of multi-photon ta...
Figure 18: A) Reductive hydrodehalogenation of aryl halides via multi-photon tandem photocatalysis. B) Selecte...
Figure 19: A) Carbonylative amidation of aryl halides in continuous flow. B) Selected examples from the substr...
Figure 20: A) General scheme for reductive (RQ) and oxidative quenching (OQ) protocols using [FeIII(btz)3](PF6)...
Figure 21: A) Carbonylative amidation of alkyl iodides with [IrIII(ppy)2(dtbbpy)]PF6. B) Selected examples fro...
Figure 22: A) Carboxylative C–N bond cleavage in cyclic amines. B) Selected examples from the substrate scope....
Figure 23: A) Formal reduction of alkenes to alkanes via transfer hydrogenation. B) Selected examples from the...
Figure 24: A) Birch-type reduction of benzenes with PMP-BPI. B) Selected examples from the substrate scope (sc...
Figure 25: Proposed mechanism of the OH− mediated conPET Birch-type reduction of benzene via generation of sol...
Figure 26: Reductive detosylation of N-tosylated amides with Mes-Acr-BF4. B) Selected examples from the substr...
Figure 27: A) Reductive detosylation of N-tosyl amides by dual PRC. B) Selected examples from the substrate sc...
Figure 28: A) Mechanism of the dual PRC based on PET between [Cu(dap)2]+ and DCA. B) Mechanism of the dual PRC...
Figure 29: A) N–O bond cleavage in Weinreb amides with anthracene. B) N–O bond cleavage in Weinreb amides rely...
Figure 30: A) Pentafluorosulfanylation and fluoride elimination. B) Mechanism of the pentafluorosulfanylation ...
Figure 31: A) α-Alkoxypentafluorosulfanylation (top) and selected examples from the substrate scope (bottom). ...
Figure 32: A) Oxidative amination of arenes with azoles catalyzed by N-Ph PTZ. B) Selected examples from the s...
Figure 33: A) C(sp3)–H bond activation by HAT via chloride oxidation by *N-Ph PTZ•+. B) Proposed mechanism for...
Figure 34: A) Recycling e-PRC C–H azolation of electron-rich arenes with pyrazoles using Mes-Acr+ as a photoca...
Figure 35: A) Radical ion e-PRC direct oxidation of unactivated arenes using TAC+ as an electro-activated phot...
Figure 36: A) Radical ion e-PRC direct oxidation of unactivated arenes using TPA as an electro-activated photo...
Figure 37: Proposed mechanism (top) and mode of preassembly (bottom).
Figure 38: A) Possible preassemblies of reactive (left) vs unreactive (right) arenes. B) Calculated spin densi...
Figure 39: A) Recycling e-PRC C(sp2 )–H acetoxylation of arenes using DDQ as a photocatalyst. B) Proposed cata...
Figure 40: Gram scale hydroxylation of benzene in a recirculated flow setup.
Figure 41: A) Radical ion e-PRC vicinal diamination of alkylarenes using TAC+ as an electro-activated photocat...
Figure 42: A) Sequential oxygenation of multiple adjacent C–H bonds under radical ion e-PRC using TAC+ as an e...
Figure 43: A) Enantioselective recycling e-PRC cyanation of benzylic C–H bonds using ADQS as photocatalyst. B)...
Figure 44: Proposed tandem mechanism by Xu and co-workers.
Figure 45: A) Enantioselective recycling e-PRC decarboxylative cyanation using Cu(acac)2, Ce(OTf)3 and a box l...
Figure 46: A) Enantioselective recycling e-PRC benzylic cyanation using Cu(MeCN)4BF4, box ligand and anthraqui...
Figure 47: A) Radical ion e-PRC acetoxyhydroxylation of aryl olefins using TAC+ as an electro-activated photoc...
Figure 48: Selected examples from the substrate scope.
Figure 49: Photoelectrochemical acetoxyhydroxylation in a recirculated flow setup.
Figure 50: A) Radical ion e-PRC aminooxygenation of aryl olefins using TAC+ as an electro-activated photocatal...
Figure 51: A) Recycling e-PRC C–H alkylation of heteroarenes with organic trifluoroborates using Mes-Acr+ as p...
Figure 52: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using CeCl3·7H2O as catalyst. B) ...
Figure 53: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using Fe(NH4)2(SO4)2·6H2O as cata...
Figure 54: A) Recycling e-PRC C–H alkylation of heteroarenes with alkyl oxalates and 4CzIPN as photocatalyst. ...
Figure 55: A) Recycling e-PRC decarboxylative C–H carbamoylation of heteroarenes using 4CzIPN as photocatalyst...
Figure 56: A) Photoelectrochemical HAT-mediated hydrocarbon activation via the chlorine radical. B) Proposed m...
Figure 57: A) Selected examples from the substrate scope. B) Gram and decagram scale semi-continuous flow PEC ...
Figure 58: A) Photoelectrochemical HAT-mediated dehydrogenative coupling of benzothiazoles with aliphatic C–H ...
Figure 59: A) Photoelectrochemical HAT activation of ethers using electro-activated TAC+ as photocatalyst. B) ...
Figure 60: Selected examples from the substrate scope.
Figure 61: A) Photoelectrochemical HAT-mediated synthesis of alkylated benzimidazo-fused isoquinolinones using...
Figure 62: A) Decoupled photoelectrochemical cerium-catalyzed oxydichlorination of alkynes using CeCl3 as cata...
Figure 63: Proposed decoupled photoelectrochemical mechanism.
Figure 64: A) Decoupled photoelectrochemical ring-opening bromination of tertiary cycloalkanols using MgBr2 as...
Figure 65: A) Recycling e-PRC ring-opening functionalization of cycloalkanols using CeCl3 as catalyst. B) Prop...
Figure 66: Selected examples from the substrate scope of the PEC ring-opening functionalization.
Figure 67: A) Radical ion e-PRC reduction of chloro- and bromoarenes using DCA as catalyst and various accepto...
Figure 68: A) Screening of different phthalimide derivatives as catalyst for the e-PRC reduction of aryl halid...
Figure 69: Screening of different organic catalysts for the e-PRC reduction of trialkylanilium salts.
Figure 70: A) e-PRC reduction of phosphonated phenols and anilinium salts. B) Selected examples from the subst...
Figure 71: A) ConPET and e-PRC reduction of 4-bromobenzonitrile using a naphthalene diimide (NDI) precatalyst ...
Figure 72: A) Radical ion e-PRC reduction of phosphinated aliphatic alcohols with n-BuO-NpMI as catalyst. B) C...
Figure 73: Selected examples from the substrate scope.
Figure 74: A) Recycling e-PRC reductive dimerization of benzylic chlorides using a [Cu2] catalyst. B) Proposed...
Figure 75: A) Decoupled photoelectrochemical C–H alkylation of heteroarenes through deamination of Katritzky s...
Figure 76: Proposed mechanism by Chen and co-workers.
Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions
- Masahiro Hosoya,
- Yusuke Saito and
- Yousuke Horiuchi
Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55
- aerobic oxidation. Photographs of the various reactors. (a) Standard tube reactor. (b) Tube reactor with a static mixer. (c) Honeycomb reactor. Proposed catalytic cycle for aerobic oxidation using Fe(NO3)3/TEMPO. Flow setup for aerobic oxidation using various flow reactors. Flow setup for high-throughput
- reactors. Reaction rate for high-throughput aerobic oxidation using the honeycomb reactor. Substrate scope and additional screening for aerobic oxidation using the standard tube reactor and the honeycomb reactor. Supporting Information Supporting Information File 100: Experimental procedures
Graphical Abstract
Figure 1: Honeycomb reactor. (a) Photograph. (b) Schematic diagram.
Scheme 1: Proposed catalytic cycle for aerobic oxidation using Fe(NO3)3/TEMPO.
Figure 2: Time course of the heat of reaction for aerobic oxidation.
Scheme 2: Flow setup for aerobic oxidation using various flow reactors.
Figure 3: Photographs of the various reactors. (a) Standard tube reactor. (b) Tube reactor with a static mixe...
Scheme 3: Flow setup for high-throughput aerobic oxidation using the honeycomb reactor.
Scheme 4: Flow setup for substrate scope and additional screening.
Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles
- Péter Kisszékelyi and
- Radovan Šebesta
Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44
- enantioselective methods for the synthesis of cyclobutylboronates which could serve as important building blocks [86]. Utilizing high-throughput (HTS) chiral ligand screening, they have presented the highly asymmetric conjugate borylation of disubstituted cyclobutenones. Next, they thoroughly studied the
Graphical Abstract
Scheme 1: General scheme depicting tandem reactions based on an asymmetric conjugate addition followed by an ...
Scheme 2: Cu-catalyzed tandem conjugate addition of R2Zn/aldol reaction with chiral acetals.
Scheme 3: Cu-catalyzed asymmetric desymmetrization of cyclopentene-1,3-diones using a tandem conjugate additi...
Scheme 4: Stereocontrolled assembly of dialkylzincs, cyclic enones, and sulfinylimines utilizing a Cu-catalyz...
Scheme 5: Cu-catalyzed tandem conjugate addition/Mannich reaction (A). Access to chiral isoindolinones and tr...
Scheme 6: Cu-catalyzed tandem conjugate addition/nitro-Mannich reaction (A) with syn–anti or syn–syn selectiv...
Figure 1: Various chiral ligands utilized for the tandem conjugate addition/Michael reaction sequences.
Scheme 7: Cu-catalyzed tandem conjugate addition/Michael reaction: side-product formation with chalcone (A) a...
Scheme 8: Zn enolate trapping using allyl iodides (A), Stork–Jung vinylsilane reagents (B), and allyl bromide...
Scheme 9: Cu-catalyzed tandem conjugate addition/acylation through Li R2Zn enolate (A). A four-component coup...
Scheme 10: Selected examples for the Cu-catalyzed tandem conjugate addition/trifluoromethylthiolation sequence....
Scheme 11: Zn enolates trapped by vinyloxiranes: synthesis of allylic alcohols.
Scheme 12: Stereoselective cyclopropanation of Mg enolates formed by ACA of Grignard reagents to chlorocrotona...
Scheme 13: Domino aldol reactions of Mg enolates formed from coumarin and chromone.
Scheme 14: Oxidative coupling of ACA-produced Mg enolates.
Scheme 15: Tandem ACA of Grignard reagents to enones and Mannich reaction.
Scheme 16: Diastereodivergent Mannich reaction of Mg enolates with differently N-protected imines.
Scheme 17: Tandem Grignard–ACA–Mannich using Taddol-based phosphine-phosphite ligands.
Scheme 18: Tandem reaction of Mg enolates with aminomethylating reagents.
Scheme 19: Tandem reaction composed of Grignard ACA to alkynyl enones.
Scheme 20: Rh/Cu-catalyzed tandem reaction of diazo enoates leading to cyclobutanes.
Scheme 21: Tandem Grignard-ACA of cyclopentenones and alkylation of enolates.
Scheme 22: Tandem ACA of Grignard reagents followed by enolate trapping reaction with onium compounds.
Scheme 23: Mg enolates generated from unsaturated lactones in reaction with activated alkenes.
Scheme 24: Lewis acid mediated ACA to amides and SN2 cyclization of a Br-appended enolate.
Scheme 25: Trapping reactions of aza-enolates with Michael acceptors.
Scheme 26: Si enolates generated by TMSOTf-mediated ACA of Grignard reagents and enolate trapping reaction wit...
Scheme 27: Trapping reactions of enolates generated from alkenyl heterocycles (A) and carboxylic acids (B) wit...
Scheme 28: Reactions of heterocyclic Mg enolates with onium compounds.
Scheme 29: Synthetic transformations of cycloheptatrienyl and benzodithiolyl substituents.
Scheme 30: Aminomethylation of Al enolates generated by ACA of trialkylaluminum reagents.
Scheme 31: Trapping reactions of enolates with activated alkenes.
Scheme 32: Alkynylation of racemic aluminum or magnesium enolates.
Scheme 33: Trapping reactions of Zr enolates generated by Cu-ACA of organozirconium reagents.
Scheme 34: Chloromethylation of Zr enolates using the Vilsmeier–Haack reagent.
Scheme 35: Tandem conjugate borylation with subsequent protonation or enolate trapping by an electrophile.
Scheme 36: Tandem conjugate borylation/aldol reaction of cyclohexenones.
Scheme 37: Selected examples for the tandem asymmetric borylation/intramolecular aldol reaction; synthesis of ...
Scheme 38: Cu-catalyzed tandem methylborylation of α,β-unsaturated phosphine oxide in the presence of (R,Sp)-J...
Scheme 39: Cu-catalyzed tandem transannular conjugated borylation/aldol cyclization of macrocycles containing ...
Scheme 40: Stereoselective tandem conjugate borylation/Mannich cyclization: selected examples (A) and a multi-...
Scheme 41: Some examples of Cu-catalyzed asymmetric tandem borylation/aldol cyclization (A). Application to di...
Scheme 42: Atropisomeric P,N-ligands used in tandem conjugate borylation/aldol cyclization sequence.
Scheme 43: Selected examples for the enantioselective Cu-catalyzed borylation/intramolecular Michael addition ...
Scheme 44: Selected examples for the preparation of enantioenriched spiroindanes using a Cu-catalyzed tandem c...
Scheme 45: Enantioselective conjugate borylation of cyclobutene-1-carboxylic acid diphenylmethyl ester 175 wit...
Scheme 46: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 47: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 48: Cu-catalyzed tandem conjugate silylation/aldol condensation. The diastereoselectivity is controlled...
Scheme 49: Chiral Ru-catalyzed three-component coupling reaction.
Scheme 50: Rh-Phebox complex-catalyzed reductive cyclization and subsequent reaction with Michael acceptors th...
Scheme 51: Rh-catalyzed tandem asymmetric conjugate alkynylation/aldol reaction (A) and subsequent spiro-cycli...
Scheme 52: Rh-bod complex-catalyzed tandem asymmetric conjugate arylation/intramolecular aldol addition (A). S...
Scheme 53: Co-catalyzed C–H-bond activation/asymmetric conjugate addition/aldol reaction.
Scheme 54: (Diisopinocampheyl)borane-promoted 1,4-hydroboration of α,β-unsaturated morpholine carboxamides and...
Figure 2: Some examples of total syntheses that have been recently reviewed.
Scheme 55: Stereoselective synthesis of antimalarial prodrug (+)-artemisinin utilizing a tandem conjugate addi...
Scheme 56: Amphilectane and serrulatane diterpenoids: preparation of chiral starting material via asymmetric t...
Scheme 57: Various asymmetric syntheses of pleuromutilin and related compounds based on a tandem conjugate add...
Scheme 58: Total synthesis of glaucocalyxin A utilizing a tandem conjugate addition/acylation reaction sequenc...
Scheme 59: Installation of the exocyclic double bond using a tandem conjugate addition/aminomethylation sequen...
Scheme 60: Synthesis of the taxol core using a tandem conjugate addition/enolate trapping sequence with Vilsme...
Scheme 61: Synthesis of the tricyclic core of 12-epi-JBIR-23/24 utilizing a Rh-catalyzed asymmetric conjugate ...
Scheme 62: Total synthesis of (−)-peyssonoside A utilizing a Cu-catalyzed enantioselective tandem conjugate ad...
Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities
- Jorge de Lima Neto and
- Paulo Henrique Menezes
Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31
- tools and new assay technologies for high throughput screening (HTS) could lead to the discovery of new analogues with more potent activities. Moreover, the study on the application of these compounds to neglected tropical diseases (NTDs), which include Chagas disease, leishmaniasis, and human African
Graphical Abstract
Figure 1: Structures of some members of the combretastatin D series, corniculatolides, and isocorniculatolide...
Scheme 1: Biosynthetic pathway proposed by Pettit and co-workers.
Scheme 2: Biosynthetic pathway towards corniculatolides or isocorniculatolides proposed by Ponnapalli and co-...
Scheme 3: Retrosynthetic approaches.
Scheme 4: Attempt of total synthesis of 2 by Boger and co-workers employing the Mitsunobu approach [27].
Scheme 5: Total synthesis of combretastatin D-2 (2) reported by Boger and co-workers employing an intramolecu...
Scheme 6: Formal synthesis of combretastatin D-2 (2) by Deshpande and co-workers using the Mitsunobu conditio...
Scheme 7: Total synthesis of combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 8: Divergent synthesis of (±)-1 form combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 9: Enantioselective synthesis of 1 by Rychnovsky and Hwang employing Jacobsen catalyst [41].
Scheme 10: Synthesis of fragment 57 by Couladouros and co-workers [43,45].
Scheme 11: Formal synthesis of compound 2 by Couladouros and co-workers [43,45].
Scheme 12: Synthesis of fragment 66 by Couladouros and co-workers [44,45].
Scheme 13: Synthesis of fragment 70 by Couladouros and co-workers [44,45].
Scheme 14: Synthesis of fragment 77 by Couladouros and co-workers [44,45].
Scheme 15: Synthesis of combretastatins 1 and 2 by Couladouros and co-workers [44,45].
Scheme 16: Formal synthesis of compound 2 by Gangakhedkar and co-workers [48].
Scheme 17: Synthesis of fragment 14 by Cousin and co-workers [50].
Scheme 18: Synthesis of fragment 91 by Cousin and co-workers [50].
Scheme 19: Formal synthesis of compound 2 by Cousin and co-workers [50].
Scheme 20: Synthesis of 2 diolide by Cousin and co-workers [50].
Scheme 21: Synthesis of combretastatin D-4 (4) by Nishiyama and co-workers [54].
Scheme 22: Synthesis of fragment 112 by Pettit and co-workers [55].
Scheme 23: Synthesis of fragment 114 by Pettit and co-workers [55].
Scheme 24: Attempt to the synthesis of compound 2 by Pettit and co-workers [55].
Scheme 25: Synthesis of combretastatin-D2 (2) starting from isovanilin (80) by Pettit and co-workers [55].
Scheme 26: Attempted synthesis of combretastatin-D2 (2) derivatives through an SNAr approach [55].
Scheme 27: Synthesis of combretastatin D-4 (4) by Pettit and co-workers [55].
Scheme 28: Synthesis of combretastatin D-2 (2) by Harras and co-workers [57].
Scheme 29: Synthesis of combretastatin D-4 (4) by Harras and co-workers [57].
Scheme 30: Formal synthesis of combretastatin D-1 (1) by Harras and co-workers [57].
Scheme 31: Synthesis of 11-O-methylcorniculatolide A (5) by Raut and co-workers [69].
Scheme 32: Synthesis of isocorniculatolide A (7) and O-methylated isocorniculatolide A 8 by Raut and co-worker...
Scheme 33: Synthesis of isocorniculatolide B (10) and hydroxyisocorniculatolide B 175 by Kim and co-workers [71].
Scheme 34: Synthesis of compound 9, 178, and 11 by Kim and co-workers [71].
Scheme 35: Synthesis of combretastatin D-2 prodrug salts [55].
Figure 2: ED50 values of the combretastatin D family against murine P388 lymphocytic leukemia cell line (appr...
Figure 3: IC50 of compounds against α-glucosidase [19].
Modern flow chemistry – prospect and advantage
- Philipp Heretsch
Beilstein J. Org. Chem. 2023, 19, 33–35, doi:10.3762/bjoc.19.3
- application, rendering this technology rather a supportive tool than a general solution [15]. Still, having this option available significantly lowers the barrier of inventing novel technological solutions and allows for high-throughput optimization in reactor design. Since different types of reactions
On drug discovery against infectious diseases and academic medicinal chemistry contributions
- Yves L. Janin
Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141
- review [62] focusing on hit selection (triage) is probably a good general starting point to describe the problem which academics are facing: “It is increasingly clear that academic high-throughput screening (HTS) and virtual HTS triage suffers from a lack of scientists trained in the art and science of
- antibacterial research department of GSK reported the results of their genome-driven seven-year long quest for original antibiotics. This target-based approach actually failed although 300 bacterial genes had been considered and 70 high-throughput screening campaigns, focusing on the corresponding proteins, had
- second original class of bacterial gyrases inhibitors. In 2004, the nitro-bearing derivative 11, resulting from a high-throughput phenotypic-based screening, was patented by Pharmacia/Pfizer for its antibacterial properties [122][123]. Even if this compound was also effective in vivo, many synthesis and
Graphical Abstract
Figure 1: Structure of halicin (1).
Figure 2: Structures of compounds 2–7.
Figure 3: Structures of compounds 8–12.
Figure 4: Structures of compounds 13–17.
Figure 5: Structures of compounds 18–21.
Figure 6: Structures of compounds 22–36 and SAR of compound 22.
Figure 7: Structures of compounds 37 and 38.
Figure 8: Structures of compounds 39–44.
Scheme 1: Retrosynthesis of pyrazolones A and B.
Scheme 2: Reaction conditions: i: HF, SbF6, CCl4. ii: (CF3SO2)2Zn, t-BuO2H, CH2Cl2/H2O.
Figure 9: Structures of compounds 49–61.
Figure 10: Structures of compounds 62–65.
Figure 11: Structures of compounds 66 and 67.
Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions
- José G. Hernández,
- Karen J. Ardila-Fierro,
- Dajana Barišić and
- Hervé Geneste
Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20
- conduct a high-throughput screening we initially carried out the milling experiments in Eppendorf vials before using standard milling jars made of stainless steel or poly(methyl methacrylate) (PMMA). This simple approach accelerated the optimization of the milling and reaction parameters [26]. From a
Graphical Abstract
Scheme 1: Examples of mechanochemical reactions using NFSI.
Scheme 2: Mechanochemical fluorination of arenes 1 with NFSI. (a) Product distributions and reaction conditio...
Figure 1: Time-resolved 2D plots of the mechanochemical reaction of: (a) 1c (0.59 mmol), NFSI (1.0 equiv), an...
Scheme 3: (a–f) Reactions of substrates 3 with NFSI. Reaction conditions: Substrates 3 (0.734 mmol) were mill...
Scheme 4: Regioselective C-3 mechanochemical amidation of 5 with NFSI.
A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis
- Theodore Groth,
- Rudiyanto Gunawan and
- Sriram Neelamegham
Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119
- public high-throughput ChIP-Seq and RNA-Seq data to identify putative TF–glycogene relationships across 29 different cancer types. Approximately three glycogenes were regulated by a given TF based on our filtering criteria, with this number ranging from 1–10. These findings are tissue-specific, as TF and
Graphical Abstract
Figure 1: A systems glycobiology framework to link multi-OMICs data. a) Cell signaling proceeds to trigger TF...
Figure 2: Analysis workflow: ChiP-Seq provides evidence of TF binding to promoter regions with 0 ≤ RP ≤ 1, qu...
Figure 3: Summary of TFs enriched to glycosylation pathways for luminal and basal breast cancer: The TFs foun...
Figure 4: Luminal breast cancer signaling pathway enrichment and glycogene connections. a) TF-to-glycogene co...
Figure 5: Basal breast cancer signaling pathway enrichments and glycogene connections. a) TF-to-glycogene com...
Figure 6: Summary of TF–glycopathway enrichments across all cancer types: TF enrichments to glycopathways acr...
Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications
- Nikita Brodyagin,
- Martins Katkevics,
- Venubabu Kotikam,
- Christopher A. Ryan and
- Eriks Rozners
Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116
Graphical Abstract
Figure 1: Structure of DNA and PNA.
Figure 2: PNA binding modes: (A) PNA–dsDNA 1:1 triplex; (B) PNA–DNA–PNA strand-invasion triplex; (C) the Hoog...
Figure 3: Structure of P-form PNA–DNA–PNA triplex from reference [41]. (A) view in the major groove and (B) view ...
Figure 4: Structures of backbone-modified PNA.
Figure 5: Structures of PNA having α- and γ-substituted backbones.
Figure 6: Structures of modified nucleobases in PNA to improve Hoogsteen hydrogen bonding to guanine and aden...
Figure 7: Proposed hydrogen bonding schemes for modified PNA nucleobases designed to recognize pyrimidines or...
Figure 8: Modified nucleobases to modulate Watson–Crick base pairing and chemically reactive crosslinking PNA...
Figure 9: Examples of triplets formed by Janus-wedge PNA nucleobases (blue). R1 denotes DNA, RNA, or PNA back...
Figure 10: Examples of fluorescent PNA nucleobases. R1 denotes DNA, RNA, or PNA backbones.
Figure 11: Endosomal entrapment and escape pathways of PNA and PNA conjugates.
Figure 12: (A) representative cell-penetrating peptides (CPPs), (B) conjugation designs and linker chemistries....
Figure 13: Proposed delivery mode by pHLIP-PNA conjugates (A) the transmembrane section of pHLIP interacting w...
Figure 14: Structures of modified penetratin CPP conjugates with PNA linked through either disulfide (for stud...
Figure 15: Chemical structure of C9–PNA, a stable amphipathic (cyclic-peptide)–PNA conjugate.
Figure 16: Structures of PNA conjugates with a lipophilic triphenylphosphonium cation (TPP–PNA) through (A) th...
Figure 17: Structures of (A) chloesteryl–PNA, (B) cholate–PNA and (C) cholate–PNA(cholate)3.
Figure 18: Structures of PNA–GalNAc conjugates (A) (GalNAc)2K, (B) triantennary (GalNAc)3, and (C) trivalent (...
Figure 19: Vitamin B12–PNA conjugates with different linkages.
Figure 20: Structures of (A) neomycin B, (B) PNA–neamine conjugate, and (C) PNA–neosamine conjugate.
Figure 21: PNA clamp (red) binding to target DNA containing a mixture of sequences (A) PNA binds with higher a...
Figure 22: Rolling circle amplification using PNA openers (red) to invade a dsDNA target forming a P-loop. A p...
Figure 23: Molecular beacons containing generic fluorophores (Fl) and quenchers (Q) recognizing a complementar...
Figure 24: (A) Light-up fluorophores such as thiazole orange display fluorescence enhancement upon binding to ...
Figure 25: Templated fluorogenic detection of oligonucleotides using two PNAs. (A) Templated FRET depends on h...
Figure 26: Lateral flow devices use a streptavidin labeled strip on nitrocellulose paper to anchor a capture P...
A new glance at the chemosphere of macroalgal–bacterial interactions: In situ profiling of metabolites in symbiosis by mass spectrometry
- Marine Vallet,
- Filip Kaftan,
- Veit Grabe,
- Fatemeh Ghaderiardakani,
- Simona Fenizia,
- Aleš Svatoš,
- Georg Pohnert and
- Thomas Wichard
Beilstein J. Org. Chem. 2021, 17, 1313–1322, doi:10.3762/bjoc.17.91
- understanding the macroalgal–bacterial interactions. The chemosphere was proposed as a region that supports chemical mediator-based cross-kingdom interactions [3]. High-throughput sequencing analysis provides the abundance and composition of the bacterial community on macroalgal surfaces [5][6]. It does not
Graphical Abstract
Figure 1: Untargeted comparative metabolomics using AP-SMALDI-HRMS highlighted metabolites involved in Ulva–b...
Figure 2: Identification of significant features associated with axenic or bacterial symbiont-associated alga ...
Figure 3: Visualisation of algae Ulva mutabilis grown under axenic conditions or with bacterial symbionts Ros...
A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries
- Guido Gambacorta,
- James S. Sharley and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90
Graphical Abstract
Figure 1: Representative shares of the global F&F market (2018) segmented on their applications [1].
Figure 2: General structure of an international fragrance company [2].
Figure 3: The Michael Edwards fragrance wheel.
Figure 4: Examples of oriental (1–3), woody (4–7), fresh (8–10), and floral (11 and 12) notes.
Figure 5: A basic depiction of batch vs flow.
Scheme 1: Examples of reactions for which flow processing outperforms batch.
Scheme 2: Some industrially important aldol-based transformations.
Scheme 3: Biphasic continuous aldol reactions of acetone and various aldehydes.
Scheme 4: Aldol synthesis of 43 in flow using LiHMDS as the base.
Scheme 5: A semi-continuous synthesis of doravirine (49) involving a key aldol reaction.
Scheme 6: Enantioselective aldol reaction using 5-(pyrrolidin-2-yl)tetrazole (51) as catalyst in a microreact...
Scheme 7: Gröger's example of asymmetric aldol reaction in aqueous media.
Figure 6: Immobilised reagent column reactor types.
Scheme 8: Photoinduced thiol–ene coupling preparation of silica-supported 5-(pyrrolidin-2-yl)tetrazole 63 and...
Scheme 9: Continuous-flow approach for enantioselective aldol reactions using the supported catalyst 67.
Scheme 10: Ötvös’ employment of a solid-supported peptide aldol catalyst in flow.
Scheme 11: The use of proline tetrazole packed in a column for aldol reaction between cyclohexanone (65) and 2...
Scheme 12: Schematic diagram of an aminosilane-grafted Si-Zr-Ti/PAI-HF reactor for continuous-flow aldol and n...
Scheme 13: Continuous-flow condensation for the synthesis of the intermediate 76 to nabumetone (77) and Microi...
Scheme 14: Synthesis of ψ-Ionone (80) in continuous-flow via aldol condensation between citral (79) and aceton...
Scheme 15: Synthesis of β-methyl-ionones (83) from citral (79) in flow. The steps are separately described, an...
Scheme 16: Continuous-flow synthesis of 85 from 84 described by Gavriilidis et al.
Scheme 17: Continuous-flow scCO2 apparatus for the synthesis of 2-methylpentanal (87) and the self-condensed u...
Scheme 18: Chen’s two-step flow synthesis of coumarin (90).
Scheme 19: Pechmann condensation for the synthesis of 7-hydroxyxcoumarin (93) in flow. The setup extended to c...
Scheme 20: Synthesis of the dihydrojasmonate 35 exploiting nitro derivative proposed by Ballini et al.
Scheme 21: Silica-supported amines as heterogeneous catalyst for nitroaldol condensation in flow.
Scheme 22: Flow apparatus for the nitroaldol condensation of p-hydroxybenzaldehyde (102) to nitrostyrene 103 a...
Scheme 23: Nitroaldol reaction of 64 to 105 employing a quaternary ammonium functionalised PANF.
Scheme 24: Enantioselective nitroaldol condensation for the synthesis of 108 under flow conditions.
Scheme 25: Enatioselective synthesis of 1,2-aminoalcohol 110 via a copper-catalysed nitroaldol condensation.
Scheme 26: Examples of Knoevenagel condensations applied for fragrance components.
Scheme 27: Flow apparatus for Knoevenagel condensation described in 1989 by Venturello et al.
Scheme 28: Knoevenagel reaction using a coated multichannel membrane microreactor.
Scheme 29: Continuous-flow apparatus for Knoevenagel condensation employing sugar cane bagasse as support deve...
Scheme 30: Knoevenagel reaction for the synthesis of 131–135 in flow using an amine-functionalised silica gel. ...
Scheme 31: Continuous-flow synthesis of compound 137, a key intermediate for the synthesis of pregabalin (138)...
Scheme 32: Continuous solvent-free apparatus applied for the synthesis of compounds 140–143 using a TSE. Throu...
Scheme 33: Lewis et al. developed a spinning disc reactor for Darzens condensation of 144 and a ketone to furn...
Scheme 34: Some key industrial applications of conjugate additions in the F&F industry.
Scheme 35: Continuous-flow synthesis of 4-(2-hydroxyethyl)thiomorpholine 1,1-dioxide (156) via double conjugat...
Scheme 36: Continuous-flow system for Michael addition using CsF on alumina as the catalyst.
Scheme 37: Calcium chloride-catalysed asymmetric Michael addition using an immobilised chiral ligand.
Scheme 38: Continuous multistep synthesis for the preparation of (R)-rolipram (173). Si-NH2: primary amine-fun...
Scheme 39: Continuous-flow Michael addition using ion exchange resin Amberlyst® A26.
Scheme 40: Preparation of the heterogeneous catalyst 181 developed by Paixão et al. exploiting Ugi multicompon...
Scheme 41: Continuous-flow system developed by the Paixão’s group for the preparation of Michael asymmetric ad...
Scheme 42: Continuous-flow synthesis of nitroaldols catalysed by supported catalyst 184 developed by Wennemers...
Scheme 43: Heterogenous polystyrene-supported catalysts developed by Pericàs and co-workers.
Scheme 44: PANF-supported pyrrolidine catalyst for the conjugate addition of cyclohexanone (65) and trans-β-ni...
Scheme 45: Synthesis of (−)-paroxetine precursor 195 developed by Ötvös, Pericàs, and Kappe.
Scheme 46: Continuous-flow approach for the 5-step synthesis of (−)-oseltamivir (201) as devised by Hayashi an...
Scheme 47: Continuous-flow enzyme-catalysed Michael addition.
Scheme 48: Continuous-flow copper-catalysed 1,4 conjugate addition of Grignard reagents to enones. Reprinted w...
Scheme 49: A collection of commonly encountered hydrogenation reactions.
Figure 7: The ThalesNano H-Cube® continuous-flow hydrogenator.
Scheme 50: Chemoselective reduction of an α,β-unsaturated ketone using the H-Cube® reactor.
Scheme 51: Incorporation of Lindlar’s catalyst into the H-Cube® reactor for the reduction of an alkyne.
Scheme 52: Continuous-flow semi-hydrogenation of alkyne 208 to 209 using SACs with H-Cube® system.
Figure 8: The standard setups for tube-in-tube gas–liquid reactor units.
Scheme 53: Homogeneous hydrogenation of olefins using a tube-in-tube reactor setup.
Scheme 54: Recyclable heterogeneous flow hydrogenation system.
Scheme 55: Leadbeater’s reverse tube-in-tube hydrogenation system for olefin reductions.
Scheme 56: a) Hydrogenation using a Pd-immobilised microchannel reactor (MCR) and b) a representation of the i...
Scheme 57: Hydrogenation of alkyne 238 exploiting segmented flow in a Pd-immobilised capillary reactor.
Scheme 58: Continuous hydrogenation system for the preparation of cyrene (241) from (−)-levoglucosenone (240).
Scheme 59: Continuous hydrogenation system based on CSMs developed by Hornung et al.
Scheme 60: Chemoselective reduction of carbonyls (ketones over aldehydes) in flow.
Scheme 61: Continuous system for the semi-hydrogenation of 256 and 258, developed by Galarneau et al.
Scheme 62: Continuous synthesis of biodiesel fuel 261 from lignin-derived furfural acetone (260).
Scheme 63: Continuous synthesis of γ-valerolacetone (263) via CTH developed by Pineda et al.
Scheme 64: Continuous hydrogenation of lignin-derived biomass (products 265, 266, and 267) using a sustainable...
Scheme 65: Ru/C or Rh/C-catalysed hydrogenation of arene in flow as developed by Sajiki et al.
Scheme 66: Polysilane-immobilized Rh–Pt-catalysed hydrogenation of arenes in flow by Kobayashi et al.
Scheme 67: High-pressure in-line mixing of H2 for the asymmetric reduction of 278 at pilot scale with a 73 L p...
Figure 9: Picture of the PFR employed at Eli Lilly & Co. for the continuous hydrogenation of 278 [287]. Reprinted ...
Scheme 68: Continuous-flow asymmetric hydrogenation using Oppolzer's sultam 280 as chiral auxiliary.
Scheme 69: Some examples of industrially important oxidation reactions in the F&F industry. CFL: compact fluor...
Scheme 70: Gold-catalysed heterogeneous oxidation of alcohols in flow.
Scheme 71: Uozumi’s ARP-Pt flow oxidation protocol.
Scheme 72: High-throughput screening of aldehyde oxidation in flow using an in-line GC.
Scheme 73: Permanganate-mediated Nef oxidation of nitroalkanes in flow with the use of in-line sonication to p...
Scheme 74: Continuous-flow aerobic anti-Markovnikov Wacker oxidation.
Scheme 75: Continuous-flow oxidation of 2-benzylpyridine (312) using air as the oxidant.
Scheme 76: Continuous-flow photo-oxygenation of monoterpenes.
Scheme 77: A tubular reactor design for flow photo-oxygenation.
Scheme 78: Glucose oxidase (GOx)-mediated continuous oxidation of glucose using compressed air and the FFMR re...
Scheme 79: Schematic continuous-flow sodium hypochlorite/TEMPO oxidation of alcohols.
Scheme 80: Oxidation using immobilised TEMPO (344) was developed by McQuade et al.
Scheme 81: General protocol for the bleach/catalytic TBAB oxidation of aldehydes and alcohols.
Scheme 82: Continuous-flow PTC-assisted oxidation using hydrogen peroxide. The process was easily scaled up by...
Scheme 83: Continuous-flow epoxidation of cyclohexene (348) and in situ preparation of m-CPBA.
Scheme 84: Continuous-flow epoxidation using DMDO as oxidant.
Scheme 85: Mukayama aerobic epoxidation optimised in flow mode by the Favre-Réguillon group.
Scheme 86: Continuous-flow asymmetric epoxidation of derivatives of 359 exploiting a biomimetic iron catalyst.
Scheme 87: Continuous-flow enzymatic epoxidation of alkenes developed by Watts et al.
Scheme 88: Engineered multichannel microreactor for continuous-flow ozonolysis of 366.
Scheme 89: Continuous-flow synthesis of the vitamin D precursor 368 using multichannel microreactors. MFC: mas...
Scheme 90: Continuous ozonolysis setup used by Kappe et al. for the synthesis of various substrates employing ...
Scheme 91: Continuous-flow apparatus for ozonolysis as developed by Ley et al.
Scheme 92: Continuous-flow ozonolysis for synthesis of vanillin (2) using a film-shear flow reactor.
Scheme 93: Examples of preparative methods for ajoene (386) and allicin (388).
Scheme 94: Continuous-flow oxidation of thioanisole (389) using styrene-based polymer-supported peroxytungstat...
Scheme 95: Continuous oxidation of thiosulfinates using Oxone®-packed reactor.
Scheme 96: Continuous-flow electrochemical oxidation of thioethers.
Scheme 97: Continuous-flow oxidation of 400 to cinnamophenone (235).
Scheme 98: Continuous-flow synthesis of dehydrated material 401 via oxidation of methyl dihydrojasmonate (33).
Scheme 99: Some industrially important transformations involving Grignard reagents.
Scheme 100: Grachev et al. apparatus for continuous preparation of Grignard reagents.
Scheme 101: Example of fluidized Mg bed reactor with NMR spectrometer as on-line monitoring system.
Scheme 102: Continuous-flow synthesis of Grignard reagents and subsequent quenching reaction.
Figure 10: Membrane-based, liquid–liquid separator with integrated pressure control [52]. Adapted with permission ...
Scheme 103: Continuous-flow synthesis of 458, an intermediate to fluconazole (459).
Scheme 104: Continuous-flow synthesis of ketones starting from benzoyl chlorides.
Scheme 105: A Grignard alkylation combining CSTR and PFR technologies with in-line infrared reaction monitoring....
Scheme 106: Continuous-flow preparation of 469 from Grignard addition of methylmagnesium bromide.
Scheme 107: Continuous-flow synthesis of Grignard reagents 471.
Scheme 108: Preparation of the Grignard reagent 471 using CSTR and the continuous process for synthesis of the ...
Scheme 109: Continuous process for carboxylation of Grignard reagents in flow using tube-in-tube technology.
Scheme 110: Continuous synthesis of propargylic alcohols via ethynyl-Grignard reagent.
Scheme 111: Silica-supported catalysed enantioselective arylation of aldehydes using Grignard reagents in flow ...
Scheme 112: Acid-catalysed rearrangement of citral and dehydrolinalool derivatives.
Scheme 113: Continuous stilbene isomerisation with continuous recycling of photoredox catalyst.
Scheme 114: Continuous-flow synthesis of compound 494 as developed by Ley et al.
Scheme 115: Selected industrial applications of DA reaction.
Scheme 116: Multistep flow synthesis of the spirocyclic structure 505 via employing DA cycloaddition.
Scheme 117: Continuous-flow DA reaction developed in a plater flow reactor for the preparation of the adduct 508...
Scheme 118: Continuous-flow DA reaction using a silica-supported imidazolidinone organocatalyst.
Scheme 119: Batch vs flow for the DA reaction of (cyclohexa-1,5-dien-1-yloxy)trimethylsilane (513) with acrylon...
Scheme 120: Continuous-flow DA reaction between 510 and 515 using a shell-core droplet system.
Scheme 121: Continuous-flow synthesis of bicyclic systems from benzyne precursors.
Scheme 122: Continuous-flow synthesis of bicyclic scaffolds 527 and 528 for further development of potential ph...
Scheme 123: Continuous-flow inverse-electron hetero-DA reaction to pyridine derivatives such as 531.
Scheme 124: Comparison between batch and flow for the synthesis of pyrimidinones 532–536 via retro-DA reaction ...
Scheme 125: Continuous-flow coupled with ultrasonic system for preparation of ʟ-ascorbic acid derivatives 539 d...
Scheme 126: Two-step continuous-flow synthesis of triazole 543.
Scheme 127: Continuous-flow preparation of triazoles via CuAAC employing 546-based heterogeneous catalyst.
Scheme 128: Continuous-flow synthesis of compounds 558 through A3-coupling and 560 via AgAAC both employing the...
Scheme 129: Continuous-flow photoinduced [2 + 2] cycloaddition for the preparation of bicyclic derivatives of 5...
Scheme 130: Continuous-flow [2 + 2] and [5 + 2] cycloaddition on large scale employing a flow reactor developed...
Scheme 131: Continuous-flow preparation of the tricyclic structures 573 and 574 starting from pyrrole 570 via [...
Scheme 132: Continuous-flow [2 + 2] photocyclization of cinnamates.
Scheme 133: Continuous-flow preparation of cyclobutane 580 on a 5-plates photoreactor.
Scheme 134: Continuous-flow [2 + 2] photocycloaddition under white LED lamp using heterogeneous PCN as photocat...
Figure 11: Picture of the parallel tube flow reactor (PTFR) "The Firefly" developed by Booker-Milburn et al. a...
Scheme 135: Continuous-flow acid-catalysed [2 + 2] cycloaddition between silyl enol ethers and acrylic esters.
Scheme 136: Continuous synthesis of lactam 602 using glass column reactors.
Scheme 137: In situ generation of ketenes for the Staudinger lactam synthesis developed by Ley and Hafner.
Scheme 138: Application of [2 + 2 + 2] cycloadditions in flow employed by Ley et al.
Scheme 139: Examples of FC reactions applied in F&F industry.
Scheme 140: Continuous-flow synthesis of ibuprofen developed by McQuade et al.
Scheme 141: The FC acylation step of Jamison’s three-step ibuprofen synthesis.
Scheme 142: Synthesis of naphthalene derivative 629 via FC acylation in microreactors.
Scheme 143: Flow system for rapid screening of catalysts and reaction conditions developed by Weber et al.
Scheme 144: Continuous-flow system developed by Buorne, Muller et al. for DSD optimisation of the FC acylation ...
Scheme 145: Continuous-flow FC acylation of alkynes to yield β-chlorovinyl ketones such as 638.
Scheme 146: Continuous-flow synthesis of tonalide (619) developed by Wang et al.
Scheme 147: Continuous-flow preparation of acylated arene such as 290 employing Zr4+-β-zeolite developed by Kob...
Scheme 148: Flow system applied on an Aza-FC reaction catalysed by the thiourea catalyst 648.
Scheme 149: Continuous hydroformylation in scCO2.
Scheme 150: Two-step flow synthesis of aldehyde 655 through a sequential Heck reaction and subsequent hydroform...
Scheme 151: Single-droplet (above) and continuous (below) flow reactors developed by Abolhasani et al. for the ...
Scheme 152: Continuous hydroformylation of 1-dodecene (655) using a PFR-CSTR system developed by Sundmacher et ...
Scheme 153: Continuous-flow synthesis of the aldehyde 660 developed by Eli Lilly & Co. [32]. Adapted with permissio...
Scheme 154: Continuous asymmetric hydroformylation employing heterogenous catalst supported on carbon-based sup...
Scheme 155: Examples of acetylation in F&F industry: synthesis of bornyl (S,R,S-664) and isobornyl (S,S,S-664) ...
Scheme 156: Continuous-flow preparation of bornyl acetate (S,R,S-664) employing the oscillating flow reactor.
Scheme 157: Continuous-flow synthesis of geranyl acetate (666) from acetylation of geraniol (343) developed by ...
Scheme 158: 12-Ttungstosilicic acid-supported silica monolith-catalysed acetylation in flow.
Scheme 159: Continuous-flow preparation of cyclopentenone 676.
Scheme 160: Two-stage synthesis of coumarin (90) via acetylation of salicylaldehyde (88).
Scheme 161: Intensification process for acetylation of 5-methoxytryptamine (677) to melatonin (678) developed b...
Scheme 162: Examples of macrocyclic musky odorants both natural (679–681) and synthetic (682 and 683).
Scheme 163: Flow setup combined with microwave for the synthesis of macrocycle 686 via RCM.
Scheme 164: Continuous synthesis of 2,5-dihydro-1H-pyrroles via ring-closing metathesis.
Scheme 165: Continuous-flow metathesis of 485 developed by Leadbeater et al.
Figure 12: Comparison between RCM performed using different routes for the preparation of 696. On the left the...
Scheme 166: Continuous-flow RCM of 697 employed the solid-supported catalyst 698 developed by Grela, Kirschning...
Scheme 167: Continuous-flow RORCM of cyclooctene employing the silica-absorbed catalyst 700.
Scheme 168: Continuous-flow self-metathesis of methyl oleate (703) employing SILP catalyst 704.
Scheme 169: Flow apparatus for the RCM of 697 using a nanofiltration membrane for the recovery and reuse of the...
Scheme 170: Comparison of loadings between RCMs performed with different routes for the synthesis of 709.
A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent
- Ke Wu,
- Yichen Ling,
- An Ding,
- Liqun Jin,
- Nan Sun,
- Baoxiang Hu,
- Zhenlu Shen and
- Xinquan Hu
Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69
- ]. This method with long perfluorinated alkyl chains is attractive in parallel synthesis and also in high-throughput biological screening. However, both the modified LR and the fluorous solvents are rather expensive and not practical for scaling up. Besides, basic aqueous solutions were utilized as well
Graphical Abstract
Figure 1: Generation of the six-membered byproduct A from thionation reactions using Lawesson’s reagent.
Figure 2: Work-up procedure for the reaction with LR.
Figure 3: Modified process for the synthesis of 2e via phase separation.
Scheme 1: Modified process for the synthesis of pincer ligand 4.
Scheme 2: Modified process for the synthesis of pincer-type ligand 6.
Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases
- Olga Gherbovet,
- Fernando Ferreira,
- Apolline Clément,
- Mélanie Ragon,
- Julien Durand,
- Sophie Bozonnet,
- Michael J. O'Donohue and
- Régis Fauré
Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30
- toolbox, providing informationally rich high-throughput screens that can not only attribute an activity to putative enzymes but also procure some qualitative details on enzyme properties. In this respect, the availability of easy-to-use chromogenic substrates that can provide both qualitative and
- natural or synthetic compounds [9][10]. The latter, which are used in high-throughput screening (HTS) assays, fall into three categories. The simplest are feruloyl esters of chromogenic moieties [11][12][13][14], such as p-nitrophenol or short-chain alkyl groups (e.g., methyl ferulate). More elaborate and
- ] containing 5-O-feruloylated α-ʟ-arabinofuranosyl moieties, but lower than that (40 IU/mg, unpublished data) measured using the more labile 4NTC–Fe. Therefore, although 4NTC–Fe is a practical synthetic probe for both the high-throughput screening and the preliminary characterization of the Fae activity [13
Graphical Abstract
Figure 1: Alternative syntheses (A) and full structures (B) of the 5-bromo-4-chloro-3-indolyl or 4-nitropheny...
Scheme 1: Chemoenzymatic synthesis of (±)-4-O-(2-hydroxy-4-nitrophenyl)-1-O-trans-feruloyl-1,2,4-butanetriol ...
Figure 2: (A) Spectrometric monitoring (at 530 nm) of 4NTC released after the action of Fae on 12 in the pres...
19F NMR as a tool in chemical biology
- Diana Gimenez,
- Aoife Phelan,
- Cormac D. Murphy and
- Steven L. Cobb
Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28
- reviewed in detail by Dalvit and Vulpetti [41][42]. The main advantages of these methods for lead compound screening is that they offer a platform not only for the rapid high-throughput screening of multiple protein small ligands, but also for the direct screening of functional inhibitors of much larger
Graphical Abstract
Figure 1: Selected examples of 19F-labelled amino acid analogues used as probes in chemical biology.
Figure 2: (a) Sequences of the antimicrobial peptide MSI-78 and pFtBSer-containing analogs and cartoon repres...
Figure 3: (a) Chemical structures of a selection of trifluoromethyl tags. (b) Comparative analysis showing th...
Figure 4: (a) First bromodomain of Brd4 with all three tryptophan residues displayed in blue and labelled by ...
Figure 5: (a) Enzymatic hydroxylation of GBBNF in the presence of hBBOX (b) 19F NMR spectra showing the conve...
Figure 6: (a) In-cell enzymatic hydrolysis of the fluorinated anandamide analogue ARN1203 catalyzed by hFAAH....
Figure 7: (a) X-ray crystal structure of CAM highlighting the location the phenylalanine residues replaced by...
Figure 8: 19F PREs of 4-F, 5-F, 6-F, 7-FTrp49 containing MTSL-modified S52CCV-N. The 19F NMR resonances of ox...
Figure 9: 19F NMR as a direct probe of Ud NS1A ED homodimerization. Schematic representation showing the loca...
Figure 10: (a) Representative spectrum of a 182 μM sample of Aβ1-40-tfM35 at varying times indicating the majo...
Figure 11: Illustration of the conformational switch induced by SDS in 4-tfmF-labelled α-Syn. Also shown are t...
Figure 12: (a) Structural models of the Myc‐Max (left), Myc‐Max‐DNA (middle) and Myc‐Max‐BRCA1 complexes (righ...
Figure 13: (a) Side (left) and bottom (right) views of the pentameric apo ELIC X-ray structure (PDB ID: 3RQU) ...
Figure 14: (a) General structure of a selection of recently developed 19F-labelled nucleotides for their use a...
Figure 15: Monitoring biotransformation of the fluorinated pesticide cyhalothrin by the fungus C. elegans. The...
Figure 16: Following the biodegradation of emerging fluorinated pollutants by 19F NMR. The spectra are from cu...
Figure 17: Discovery of new fluorinated natural products by 19F NMR. The spectrum is of the culture supernatan...
Figure 18: Application of 19F NMR to investigate the biosynthesis of nucleocidin. The spectra are from culture...
Figure 19: Detection of new fluorofengycins (indicated by arrows) in culture supernatants of Bacillus sp. CS93...
Figure 20: Measurement of β-galactosidase activity in MCF7 cancer cells expressing lacZ using 19F NMR. The deg...
Figure 21: Detection of ions using 19F NMR. (a) Structure of TF-BAPTA and its 19F iCEST spectra in the presenc...
Figure 22: (a) The ONOO−-mediated decarbonylation of 5-fluoroisatin and 6-fluoroisatin. The selectivity of (b)...
Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification
- Steffen Lippold,
- Arnoud H. de Ru,
- Jan Nouta,
- Peter A. van Veelen,
- Magnus Palmblad,
- Manfred Wuhrer and
- Noortje de Haan
Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253
- approach is applicable when the identity and elution behavior of the glycopeptides of interest is known and is aided by quality criteria such as mass accuracy and isotopic pattern matching. Furthermore, such approaches allow quantification in a high-throughput manner, which is advantageous e.g., in clinal
- provides a powerful workflow towards high-throughput glycopeptide analysis. Experimental Sample, chemicals, and enzymes Human plasma Visucon-F was obtained from Affinity Biologicals (Ancaster, ON, Canada). Affinity matrix beads for IgG (CaptureSelect FcXL, capacity 25–35 g/L) and IgA (CaptureSelect IgA
Graphical Abstract
Figure 1: Integration of automated glycopeptide identification by Byonic and GlycopeptideGraphMS (aided by Op...
Figure 2: Representative IgG and IgA glycopeptide clusters detected by GlycopeptideGraphMS.
Figure 3: Representative GlycopeptideGraphMS output for peptides of interest. Assigned compositions were iden...
Figure 4: Comparison of quantification results obtained by manual integration of EICs in Skyline (black), aut...
Secondary metabolites of Bacillus subtilis impact the assembly of soil-derived semisynthetic bacterial communities
- Heiko T. Kiesewalter,
- Carlos N. Lozano-Andrade,
- Mikael L. Strube and
- Ákos T. Kovács
Beilstein J. Org. Chem. 2020, 16, 2983–2998, doi:10.3762/bjoc.16.248
- for 30 s, 62 °C for 30 s, 72 °C for 30 s, and finally, 72 °C for 5 min. All V3-V4 amplicons were purified using the NucleoSpin gel and PCR cleanup kit (Macherey-Nagel) and pooled in equimolar ratios. The amplicon pool was submitted to Novogene Europe Company Limited (United Kingdom) for high
- -throughput sequencing on an Illumina NovaSeq 6000 platform with 2 million reads (2 × 250 bp paired-end reads). Raw sequence data is available at NCBI: PRJNA658074. Sequencing data preprocessing The multiplexed sequencing data was imported into the QIIME 2 pipeline (version 2020.6) [65][66]. The paired-end
Graphical Abstract
Figure 1: Overview of the NRPs surfactin, plipastatin, bacillibactin, and iturin as well as the hybrid NRP-PK...
Figure 2: Overview of the experimental setup. A soil suspension, obtained from a soil sample, was used as an ...
Figure 3: The taxonomic summaries are showing the relative abundance of the most abundant genera for each rep...
Figure 4: Diversity analyses of the soil sample (“Soil”), 12 h preincubated soil suspensions (“Pre”), and unt...
Figure 5: Abundance ratios for each genus and replicate (points) in the control community compared to the WT-...
Figure 6: The relative abundance of Lysinibacillus in the untreated (“Control”) and treated mock communities ...
Figure 7: Growth curves of L. fusiformis M5 exposed to spent media from 48 h B. subtilis cultures and without...
Figure 8: Growth curves of L. fusiformis M5 exposed to different concentrations of surfactin, the highest con...
Figure 9: Overview on the biosynthetic pathways of surfactin (A), plipastatin (B), and bacillaene (C) produce...
Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors
- Emine Kayahan,
- Mathias Jacobs,
- Leen Braeken,
- Leen C.J. Thomassen,
- Simon Kuhn,
- Tom van Gerven and
- M. Enis Leblebici
Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202
- and the problems related to scaling up are comparable. Our aim is to give an overview on the scale-up of photochemical reactions by discussing transport phenomena and technical challenges. In addition, we are assessing several high-throughput structured photoreactors using the PSTY to reveal the
Graphical Abstract
Figure 1: The momentum transport affects the mass transfer and the light field. All transport phenomena need ...
Figure 2: Common photomicroreactor designs: (a) Straight channel, (b) serpentine channel, (c) square serpenti...
Figure 3: Benchmarked photoreactors: (a) Microcapillaries in parallel, (b) microcapillaries in series, (c) fl...
Figure 4: Photochemical reactions that are detailed in Table 1.
Figure 5: Structured reactors designed for enhancing the mass transfer: (a) Packed bed photoreactor, (b) mono...
Figure 6: Comparison of the LED board designs of photomicroreactors: (a) CC array design, (b) MC array design...
Figure 7: Illustration of the light scattering phenomenon inside a photocatalytic flow reactor.
Figure 8: Efficiency of the absorption process in scattering situations with respect to pure absorption situa...
Figure 9: Different types of distributors: (a) Traditional or consecutive manifold, (b) bifurcation unit dist...
