New tandem Ugi/intramolecular Diels–Alder reaction based on vinylfuran and 1,3-butadienylfuran derivatives

• Yuriy I. Horak,
• Roman Z. Lytvyn,
• Andrii R. Vakhula,
• Yuriy V. Homza,
• Nazariy T. Pokhodylo and
• Mykola D. Obushak

Beilstein J. Org. Chem. 2025, 21, 444–450, doi:10.3762/bjoc.21.31

• reactions, for instance, have contributed to high-throughput screening for drug discovery, facilitating the identification of new therapeutic compounds. [9][10]. A notable example is ivosidenib, approved in 2018, which was synthesized using the Ugi reaction to target mutated IDH1 in acute myeloid leukemia

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• with the Negishi cross-coupling step in a continuous flow manner [41][42][43]. Continuous flow chemistry offers superior control over reaction parameters compared to traditional batch methods. This approach leads to reproducible reactions, improved safety features, and it can facilitate high-throughput

• screening and rapid optimization [46][47]. Homogenous heating and mixing in flow reactors can lead to higher reaction rates and yields. In terms of photochemistry, continuous flow setups provide enhanced light irradiation as well [48][49]. These advantages make flow chemistry a powerful tool for chemical

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• peptide structures. The remaining challenges include combining various post-translational modifications and developing a medium to high throughput screening approach to subject interesting peptide drug candidates to various MTs and perform SAR studies (structure–activity relationship). Overall, RiPP MTs

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• developing novel inhibitors of integrin function, we identified a drug candidate (10n) through high throughput screening (HTS) that inhibits the integrin complex formation, which is an important step for integrin activation. The binding inhibitor 10n was effective as IC50 of 190 μM in AlphaScreen system, and

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

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

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

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

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

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

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 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

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

• 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

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

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

• 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

Models of necessity

• Timothy Clark and
• Martin G. Hicks

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

• -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

• 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

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• compounds makes them attractive for library generations and sequential biological testing [15][16]. Although several classical synthetic procedures were developed [17][18][19][20][21], more effective and facile syntheses for a large number of compounds are still required for high throughput screening in

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• , remain to be explored [152]. One major bottleneck in these studies is the lack of high-throughput screening tools for terpenoid production and characterization. Most terpenoids do not have any chromogenic groups and their detection still relies on liquid chromatography–mass spectrometry setups, limiting

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• found to be 36, 62 and 10 μM, respectively. High-throughput screening initiatives have gained popularity in the past two decades and have become the prevailing approach to identify leads in medicinal chemistry research [77][78]. However, due to the intrinsic features of PPIs, these are not amenable to

• targeted the ZipA/FtsZ protein–protein interaction was first investigated by scientists at Wyeth Research. In this study, a fluorescence polarization-based high-throughput screening of 250,000 corporate compounds led to the identification of pyridylpyrimidine 34 (Figure 8), which was shown to be the most

• a challenge. Thus far, extensive in silico and high throughput screening campaigns of libraries of compounds, combinatorial synthesis and structure-based design approaches, biophysical screening techniques (i.e., fluorescence polarization, surface plasmon resonance and differential scanning

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• generation of protein mutant libraries and high throughput screening processes to select for variants with improved traits. Protein mutant libraries are produced from gene libraries, which are generated by random mutagenesis at DNA level. Often polymerase chain raction (PCR)-based methods like error-prone

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• discovery process [47]. The chemical library has to go through high-throughput screening (about 100,000 compounds/day approximately) using robots [48]. In multistep synthesis off-line analysis actually becomes a bottleneck as it does not allow the real-time changes to be imposed at the inlet conditions for

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• in diterpene biosynthetic routes entail time-consuming genome-mining and high-throughput screening technologies [64][65]. Additionally, the number of currently available, even partly annotated plant genomes and crystal structures of diterpene synthases is still limited. Yet, in order to establish