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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Tools for generating and analyzing glycan microarray data

• Akul Y. Mehta,
• Jamie Heimburg-Molinaro and
• Richard D. Cummings

Beilstein J. Org. Chem. 2020, 16, 2260–2271, doi:10.3762/bjoc.16.187

• which is appropriately functionalized [24][25]. Such a slide can then be used to probe GBPs or pathogens using an ELISA-like sandwich assay at microscale. This enables a high-throughput screening of glycan-mediated interactions. In this review we describe how glycan microarrays are generated, how a

GlypNirO: An automated workflow for quantitative N- and O-linked glycoproteomic data analysis

• Toan K. Phung,
• Cassandra L. Pegg and
• Benjamin L. Schulz

Beilstein J. Org. Chem. 2020, 16, 2127–2135, doi:10.3762/bjoc.16.180

• automated software pipeline which integrates the complementary outputs of Byonic and Proteome Discoverer to allow high-throughput automated quantitative glycoproteomic data analysis. The output of GlypNirO is clearly structured, allowing manual interrogation, and is also appropriate for input into diverse

• at specific sites on selected plasma glycoproteins. GlypNirO will be a useful tool for enabling robust high-throughput quantitative glycoproteomics. Experimental Byonic and Proteome Discoverer analysis We identified glycopeptides and peptides using Byonic (Protein Metrics, v. 3.8.13) searching all

Clustering and curation of electropherograms: an efficient method for analyzing large cohorts of capillary electrophoresis glycomic profiles for bioprocessing operations

• Ian Walsh,
• Matthew S. F. Choo,
• Sim Lyn Chiin,
• Amelia Mak,
• Shi Jie Tay,
• Pauline M. Rudd,
• Yang Yuansheng,
• Andre Choo,
• Ho Ying Swan and
• Terry Nguyen-Khuong

Beilstein J. Org. Chem. 2020, 16, 2087–2099, doi:10.3762/bjoc.16.176

• , Faculty of Engineering, National University of Singapore (NUS), Singapore 117575 10.3762/bjoc.16.176 Abstract The accurate assessment of antibody glycosylation during bioprocessing requires the high-throughput generation of large amounts of glycomics data. This allows bioprocess engineers to identify

• antibody glycosylation accurately, high-throughput analysis of hundreds to thousands of profiles is required for the identification of critical process parameters that control the glycosylation CQAs [8]. For complete bioprocessing analysis, favorable glyco-analytical methods need to convey a qualitative

• description of the glycans, their relative abundance, and most importantly be high-throughput in terms of quantity, comprehensiveness, and speed of data generation. Capillary electrophoresis-laser-induced fluorescence (CE-LIF) is a glycomic analytical technology that has been adapted for automated and high

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• ), here exemplified by asparagusic acid. A persistent challenge in this evolution is the simultaneous and quantitative detection of cytosolic delivery and cytotoxicity in a high-throughput format. Here, we show that the combination of the HaloTag-based chloroalkane penetration assay (CAPA) with automated

• on the endosomal uptake and release. However, a better binding affinity to DNA does not necessarily mean a higher DNA transfection efficiency. As an example, two GCP-modified peptide tweezers 14 with nanomolar dissociation constants, identified by the high-throughput screening of a combinatorial

• ][58] has been suggested to further improve the standards set by the CAPA [59]. Standard high-throughput (HT) screening has been used regularly to facilitate studies on cellular uptake [60]. In standard assays, a single macroscopic parameter, usually the fluorescence intensity, is automatically

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• fragments thereof serve equally well as descriptors [70]. Thus, with very few exceptions based on physical observables such as the molecular electrostatic potential [35], cheminformatics, including the use of ML and AI, is based on Lewis structures. Even the widespread fingerprints used for very high

• -throughput screening [71] are based on the occurrence of patterns within the Lewis structure. For chemists, the Lewis structure represents both metadata for AI/ML and an essential language for communication. However, like language, the Lewis model is context dependent (aromatic bonds, boron bonding…) and

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• high-throughput reaction screening, both of which are progressive areas of chemical research [69][70][71][72][73]. 2 Heterogeneous photocatalysts Probably the first report of HPC was published by Renz in 1921, who observed the partial reduction of titania (TiO2) in the presence of glycerol when

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• desired. Recent years have seen the emergence of new methods of research in chemistry and process development, which include high-throughput experiments [3], autonomous self-optimising reactors [4][5][6], as well as predictions of reaction outcomes and of reaction conditions based on machine learning (ML

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• and at low cost which enables high-throughput chemical and genetic screening studies. It is often difficult or impossible to undertake comparable studies on parasitic worms due to the challenges of maintaining parasitic worms outside their host, although rodent models are available for many classes of

• anthelmintic drug targets from a parasitic worm [95][96]. These approaches are still in their infancy, but such genetic modifications can give rise to scorable phenotypes reflecting the properties of the parasite drug target which may in future lend themselves to high-throughput chemical and genetic (RNAi

• and viability Several groups have developed image acquisition and analysis systems for high-throughput phenotypic screening of parasites (Table 3), typically using the approach of thresholding difference images/movies to quantify motility, sometimes segmenting the image by recognising the organism of