Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• reactors; data processing; high-throughput experimentation; machine learning; reaction optimization; Introduction Organic synthesis plays a crucial role in drug discovery, polymer synthesis, materials science, agrochemicals, and specialty chemicals. Their synthesis and process optimization require

• review follows the steps presented in Figure 1. In the following section, we review the high-throughput platforms currently used to perform chemical reaction optimization. Thereafter, we discuss the development and use of analytical tools and data processing algorithms. After that, we discuss the latest

• analytics, and data processing methods to streamline repetitive experimental tasks, reduce manual intervention, and increase the rate of experimental execution in comparison to traditional manual experimentation. In conventional chemical synthesis, several sequential steps are typically undertaken

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• proposed, we believe more research in this direction can be beneficial to the performance and reliability of machine learning models. Ideally, a unified standard data processing workflow should be established in the future to benefit various reaction prediction and synthesis tasks. Reaction representations

• into real-time adaptive systems that learn from each experiment. The discussions in this review about global and local models underline the critical need for large, comprehensive, and coherent datasets. Advancements in data processing and model training methodologies, such as transfer learning and

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• set up labile, open and closed searches and how we recalculated the published MS data for different linkers in this review can be downloaded from the publicly available database (PRIDE data set identifier PXD043402) [65]. Furthermore, the data processing can be adjusted and paralleled accordingly

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• inhibition were averaged. The percentage of inhibition was derived by analyzing the 16 h growth curve data using the standard protocol established in our laboratory, comparing the growth curves obtained across the conducted experiments. All data processing and final figures were generated using Prism

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• isomer. Data processing of spectroscopic measurements was realized with the help of Microsoft® Excel® and Igor Pro from WaveMetrics, Inc (versions 7 to 9). Isothermal titration calorimetry: LecA was expressed and purified as previously described [42]. All experiments were performed at 25 °C with an

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• reported to one decimal point unless an additional digit was required to distinguish overlapping peaks. Software for data processing: MestReNova, version 11.0.0–17609 (MestReLab Research S.L.). High-resolution mass spectrometry (HRMS) data were recorded on a Waters Micromass LCT LC–TOF instrument using

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

• and storing entire NMRium projects in their current state, whether partially or fully analyzed. Features of NMRium What differentiates NMRium from most other NMR data processing software, specifically with respect to its educational application, is the ability to handle NMR data (proprietary format of

• (practical laboratory classes including examples of synthesis and compound characterization), NMRium provides a full 1D FT workflow and therefore an ideal possibility to introduce basic concepts of data processing, data presentation, and data evaluation. Spectra from most NMR instruments may be directly used

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

• ]. Advances in MS technologies tremendously enhanced the detection and informative fragmentation of glycopeptides in the past years [9]. The large amount of highly complex data acquired using these technologies shifted the major bottleneck in glycopeptide analysis to the data processing steps. Next to the

• been made in recent years in the development of bioinformatic tools to facilitate and automate data processing in glycopeptide-centered glycoproteomics [12]. Several reports have reviewed the functionalities and application areas of data analysis tools in the field of glycoproteomics [7][9][12][13]. MS

• other than IgG and IgA were not considered for further data processing (e.g., fibrinogen, alpha-1-antitrypsin, or clusterin, see Table S1A–E, Supporting Information File 1). Missed-cleavage variants were assigned for IgG1, IgG2/3, and IgA1/2 (Asn263) but not further considered because of their low

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• nomenclatures available to describe each monosaccharide, representing and encoding a glycan structure into a file is required for communication among scientists as well as for data processing. As a consequence, glycobiologists have proposed different graphical representations, with symbols or chemical

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

• to extraneous factors such as poor printing due to a flaw in the surface, spot overlap/fusion with adjacent spot or presence of dust particles are flagged with a “bad” (or some numeric value) flag, so as to be disregarded in the data processing. The software then provides a results file as an output

• photomultiplier tube gain (also called PMT Gain). The image produced is saved as a TIFF image, usually with headers which describe the scanner settings used to acquire the image, and the intensity at each pixel is saved as the relative fluorescence units (RFU) for those scan settings. Spot alignment and data

• processing Once the image is acquired, the image is aligned to an array map (for GenePix scanners this is called the GenePix Array List file or .gal file), which indicates the coordinates of the various spots by (row, column) numbers correlated to the material which was printed at those positions. The

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

• compared qualitatively and quantitatively. For capillary electrophoresis-based glycomics data processing, this is complicated by heterogenous glycan peaks which may not fit under a Gaussian approximation. As such, automated Gaussian fitting of these peaks will yield inaccurate representation of the glycans

Models of necessity

• Timothy Clark and
• Martin G. Hicks

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

• Figure 3, is the subject of this article. It means that just about all practical chemistry and most data-processing applications in chemistry depend entirely on bonding models that are not inherent in the, as far as we know correct, quantum mechanical description of the model. In reality, even the

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• . The APEX 2 v.2014.11.0 software was used for all data processing [53]. The structure was solved and refined with SHELX [54] programs, ShelXT and ShelXL by using OLEX 2 software [55]. Hydrogen atoms were placed at idealized positions and refined. Crystallographic data (excluding structure factors) for

Preparation of anthracene-based tetraperimidine hexafluorophosphate and selective recognition of chromium(III) ions

• Qing-Xiang Liu,
• Feng Yang,
• Zhi-Xiang Zhao,
• Shao-Cong Yu and
• Yue Ding

Beilstein J. Org. Chem. 2019, 15, 2847–2855, doi:10.3762/bjoc.15.278

• and excitation spectral lines were adjusted to 5 and 10 nm. The emission spectra were recorded in the range of 375–500 nm. The program Origin 8.0 was employed for data processing. UV–vis titrations For UV–vis titrations, the sample solutions were prepared analogously to fluorescence titrations. The

• concentration of 3 was adjusted to 1.0⋅10−6 M while the concentration of Cr3+ ranged between 0.0 and 36.0⋅10−6 M. The absorption spectra were recorded at 240–300 nm. Origin 8.0 was employed for data processing. X-ray analysis Diffraction data of 3 were collected by a Bruker Apex II CCD diffractometer [56

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• ) mode at −70 eV. The ion source temperature was 250 °C and the detector voltage was set to −2236.8 V. Ions in the mass range 35–250 amu were acquired at a rate of 100 spectra s−1. All samples were analyzed in triplicate. Data analysis Data processing was performed using the software ChromSpace (Markes

Efficiency Eff_syn of complex syntheses as multicomponent reactions, its algorithm and calculations based on concrete criteria

• Heiner Eckert

Beilstein J. Org. Chem. 2019, 15, 1425–1433, doi:10.3762/bjoc.15.142

• are highly suitable for electronic data processing (EDP). This algorithm is also suitable as a basis for fair cost assessment of complex chemical syntheses. Keywords: efficiency; efficiency algorithm; multicomponent; overall yield; synthesis algorithm; synthesis efficiency; synthesis evaluation

• syntheses and quantitatively compare them with alternative syntheses with regards to their synthesis efficiency Effsyn. The mathematical operations are highly suitable for electronic data processing (EDP), as is the algorithm itself. Due to the concrete criteria, this algorithm is also suitable as a basis

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

A permutation approach to the assignment of the configuration to diastereomeric tetrads by comparison of experimental and ab initio calculated differences in NMR data

• Przemysław J. Boratyński

Beilstein J. Org. Chem. 2017, 13, 2478–2485, doi:10.3762/bjoc.13.245

• the algorithm a permutation with a highest rank is identified. The major limitation is how accurately the experiment is predicted by the DFT calculation. This is, however, a central problem and any data processing will fail in cases where the computed data do not agree with the experiment

Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin

• Spyros D. Chatziefthimiou,
• Mario Inclán,
• Petros Giastas,
• Athanasios Papakyriakou,
• Konstantina Yannakopoulou and
• Irene M. Mavridis

Beilstein J. Org. Chem. 2017, 13, 1572–1582, doi:10.3762/bjoc.13.157

• radius detector. The DENZO and SCALEPACK [40] software were used for data processing and scaling, respectively. The unit cell parameters and their esds were determined by the least square method from the high resolution frames of the collected data. The structure was solved by the isomorphous replacement

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• results from automatic post-experiment data processing protocols [28]. The synergy among these components has recently given rise to completely automated data collection experiments [29]. Glycoproteins In recent years, the expression and production of recombinant proteins was of great benefit to the whole

Dynamics and interactions of ibuprofen in cyclodextrin nanosponges by solid-state NMR spectroscopy

• Monica Ferro,
• Franca Castiglione,
• Nadia Pastori,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2017, 13, 182–194, doi:10.3762/bjoc.13.21

• outcome of VCT data processing is a “dynamic fingerprint” that can be used for the characterization of the polymer-drug system. In general, the CP-VCT methodology can be exploited to provide a dynamic characterization of polymeric systems which are expected to be structurally similar, as recently

Mono- and multilayers of molecular spoked carbazole wheels on graphite

• Stefan-S. Jester,
• A. Vikas Aggarwal,
• Daniel Kalle and
• Sigurd Höger

Beilstein J. Org. Chem. 2014, 10, 2783–2788, doi:10.3762/bjoc.10.295

• (while imaging) by applying short voltage pulses. All STM images were calibrated by subsequent immediate acquisition of an additional image at reduced bias voltage, therefore the atomic lattice of the HOPG surface is visible, which is used as a calibration grid. Data processing, also for image

Self-assembled monolayers of shape-persistent macrocycles on graphite: interior design and conformational polymorphism

• Joscha Vollmeyer,
• Friederike Eberhagen,
• Sigurd Höger and
• Stefan-S. Jester

Beilstein J. Org. Chem. 2014, 10, 2774–2782, doi:10.3762/bjoc.10.294

• immediate acquisition of an additional image at reduced bias voltage, therefore the atomic lattice of the HOPG surface is visible, which is used as a calibration grid. Data processing, also for image calibration, was performed using the SPIP 5 (Image Metrology) software package. (a), (b) Two distinguishable

Anomalous diffusion of Ibuprofen in cyclodextrin nanosponge hydrogels: an HRMAS NMR study

• Monica Ferro,
• Franca Castiglione,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2014, 10, 2715–2723, doi:10.3762/bjoc.10.286

• of the investigated samples were carried out by varying Δ in the range of 0.05–0.2 s, while the δ values were in the range of 1.4–3 ms. The pulse gradients were incremented from 2 to 95% of the maximum gradient strength in a linear ramp. The temperature was set at 305 K (32 °C). Data processing and