Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• protein – this concept is underexplored in the field of RNA drugging [37]. Recent studies suggest that the validation of RNA–small molecule interactions [38][39][40], drug efficacy or the identification of off-target effects of approved drugs on the transcriptome [41][42] could greatly benefit from

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• ], which in many cases is the only way to understand pure substituent effects (e.g., on catalysis). To enable the validation of this process, experimentalists must collect data relevant to benchmarking computations: binding constants, kinetic barriers, crystal structures. In turn, this process will be

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

• -throughput systems or in-house designed reaction modules; (iii) data collection by in-line/offline analytical tools; (iv) mapping the collected data points with the target objectives; (v) prediction of the next set of reaction conditions towards attaining optimal solutions; and (vi) experimental validation

Chemical glycobiology

• Elisa Fadda,
• Rachel Hevey,
• Benjamin Schumann and
• Ulrika Westerlind

Beilstein J. Org. Chem. 2025, 21, 8–9, doi:10.3762/bjoc.21.2

• methods that underlie modern glycobioinformatics approaches [15]. Validation of glycoprotein structure is an important aspect of contemporary structural biology, and Dialpuri et al. present the Privateer database to allow for facile quality control of such structures [16]. Finally, Barillot et al. bridge

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• (d,p) level of theory using the M062X/6-31G(d,p) optimized structures. Electronic energies obtained at both levels of theory (M062X/6-31G(d,p)//M062X/6-31G(d,p) and M062X/6-311++G(d,p)//M062X/6-31G(d,p)) were used together in subsequent estimations. Validation of the method against experimental data

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

• extensive effort. This involves complex parameter optimization, meticulous validation against experimental data, and careful consideration of diverse reaction conditions and possible reaction mechanisms [28][29]. Although some studies employ transition-state (TS) theory to simulate activation energies and

• ]. However, this approach requires careful validation of the training data coverage and the extrapolation ability of the surrogate models. Reaction-level descriptors based on DFT calculations of the TS structures of chemical reactions can provide valuable insights for predicting rate constants [113][114][115

Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling

• Jiapeng Guo,
• Weike Su and
• An Su

Beilstein J. Org. Chem. 2024, 20, 2408–2420, doi:10.3762/bjoc.20.205

• k (Figure 7a). Similar trends were reported in the nitration of nitrobenzene [40] and o-nitrotoluene [18], suggesting that the phenomenon observed in our study is not isolated. Validation, extrapolation, and optimization To validate the kinetic model and assess its ability to extrapolate, we

• beyond the modeling range (extending from the initial 1–5 minutes to 5–12 minutes in validation experiments). Compared to the original patent [2], the reaction time has been significantly reduced from tens of minutes to hours to less than 20 minutes while maintaining a lower sulfuric acid mass fraction

• ) Validation of reaction kinetic models with different mass fractions of sulfuric acid (from top to bottom: the theoretical response surfaces and experimental values are shown for sulfuric acid mass fractions of 94% and 98%, respectively). c) Response surface of the kinetic model under optimized conditions 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

• gel and subjected to MS analysis to identify the labeled proteins [77][78]. The in-gel analysis is often used for target validation with corresponding protein mutants or knockout cell lines, with loss of the identified probe–protein interaction leading to disappearance of the fluorescence band from

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• elements such as the chosen template structure (if any), the sequence alignment, and the choice of the modelling algorithm. To ensure a high accuracy of the predicted model, which should be at least comparable to that of experimental structures, several programs can be employed for model validation and

• , and the departure of the side chain χ torsion angles from expected values. Improvement and/or validation of modelled or experimentally solved structures can be also obtained by using CASP (critical assessment of protein structure prediction) [99], which consists of a free platform established in 1994

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

• to expand our in-house DEL BB collection, we sought to develop a synthetic route capable of providing a broad range of α-heteroaryl-α-amino acids in a cost-effective manner (Scheme 1c). Herein, we describe the synthesis and on-DNA validation of non-canonical α-heteroaryl-α-amino acids. We envisioned

• on gram scale starting from 2.1 g of 2-bromobenzothiazole (1i). The gram scale production showed comparable results to those obtained in the small-scale procedure, leading to the formation of 1.8 g (67% overall yield) of the final product 6i (Scheme 7, bottom). On-DNA validation Due to the large

• complexity of DELs, there is only limited opportunity to track the efficiency of individual reactions during library synthesis. Therefore, BBs need to pass validation before being used in library synthesis settings. For these bifunctional amino esters, we performed a three-step validation where they were

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• randomly shuffled cross-validation. Within each fold, the original training set is further split randomly into a new training set (90% of the original training set) and a validation set (10% of the original training set). This allows us to evaluate different models and estimate their performance. Hereafter

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• were obtained successfully (SSR = 85%, average yield of 37%) (Scheme 2). Chemical space generation Since validation of the GBB reaction showed that it is compatible with the main readily accessible chemical space criteria (at least 80% synthesizability) [30], we have aimed at the generation of the

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

• due to stronger unfavorable entropy, they are in general of lower affinity. The validation of this proof-of-concept and the dissection of thermodynamics of binding will help for the further development of lectin ligands that can be controlled by light. Keywords: carbohydrates; glycosyl azobenzenes

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• bond together with a DH, locates in the A1-type clade, in agreement with its stereoselectivity [35]. Lastly, we applied our prediction criteria for the previously mis-predicted or unpredictable β-module KRs, for example due to having both LDD and W motifs, for validation. Among nine KRs we analyzed

Monitoring carbohydrate 3D structure quality with the Privateer database

• Jordan S. Dialpuri,
• Haroldas Bagdonas,
• Lucy C. Schofield,
• Phuong Thao Pham,
• Lou Holland and
• Jon Agirre

Beilstein J. Org. Chem. 2024, 20, 931–939, doi:10.3762/bjoc.20.83

• scientists. The Privateer software is a validation and analysis tool that provides access to a number of metrics and links to external experimental resources, allowing users to evaluate structures using carbohydrate-specific methods. Here, we present the Privateer database, a free resource that aims to

• complement the growing glycan content of the PDB. Keywords: carbohydrates; database; N-glycans; N-glycosylation; polysaccharides; validation; website; Introduction Carbohydrate modelling is an important but often cumbersome stage in the macromolecular X-ray structure solution workflow. The accurate

• new resources, including services and databases [9][10][11][12][13], and standalone software [14][15][16][17][18]. Among these, the Privateer software package has been a key tool for glycoprotein and protein–carbohydrate complex validation: Privateer analyses the conformational plausibility of each

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• disruption plasmid, pGM160-ΔvarG. The cassette was sequenced for validation. The disruption plasmid was introduced into E coli S17-1 λpir by electroporation. Both Variovorax sp. H002 and E. coli S17-1 λpir were cultured overnight at 30 °C in 2xR2A and LB, respectively. The overnight cultures were washed with

• , Ser: serine, Pro: proline, Orn: ornithine). (b) Validation of var biosynthetic gene cluster. The plasmid constructed for the generation of the varG null-mutant strain (varG::cmR) using the cmR gene cassette (left), and HPLC-profile comparison of the Variovorax sp. H002 wild type strain and the varG

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• annotations and in vivo studies [8]. However, validation by in vitro approaches or biochemical analysis of the individual enzymes is lacking. Here, we verify that Hyg17 is a myo-inositol dehydrogenase and show that it has a distinct substrate scope. In addition, we use sequence similarity networks to compare

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• ) protodeauration (Scheme 1), the depth of experimental mechanistic validation achieved for allenes and alkynes have not been reproduced with alkenes. In an important foundational study by Toste, the expected alkylgold intermediate from intramolecular alkene hydroamination was isolated, however, turnover

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

• ), which we contrasted with the established R-type lectin Ricinus communis agglutinin 1 (RCA1). We also report binding of specific glycosaminoglycan subtypes and a general enhancement of binding by sulfation. Further validation using agglutination, thermal shift assays, and surface plasmon resonance

• ]. Multiple iterations of anisotropic restrained maximum likelihood refinement using REFMAC 5.8 [38] and manual building using Coot [39] were performed. Hydrogen atoms were added in their riding positions during refinement and 5% of the observations were set aside for cross-validation analysis. Upon

• inspection of the electron density maps, carbohydrate moieties were introduced and checked using Privateer [40]. The final model was validated using the wwPDB validation server (https://validate-rcsb-1.wwpdb.org). Structure figures were made using PyMol 2.5.7 and ChimeraX 1.6 [31]. The parameters for CH−π

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

• ; structure elucidation; Introduction For the validation of molecular structures, nuclear magnetic resonance (NMR) spectroscopy is an indispensable methodology in the daily routine of synthetic chemistry laboratories. Arguably, NMR experiments serve as the ‘eye of the synthetic chemist’ because they allow a

• grasp functionality would make it a preselected tool for the review process of chemistry publications. Future developments of NMRium include the processing of 2D NMR experiments, as well as a CASE- and prediction-supported assignment tool with an integrated validation function for assigned data [44

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

• the present study. For this study, a first set of 33 labelled experimental spectra obtained as described previously [4] were collected for training and validation of the model. The standard instrumental conditions for recording MS–IR data consist in a laser-enabled mass spectrometer equipped with a 3D

• category of molecules. Finally, 70% of them were used for training of the models, and 30% were used for validation. The composition of the datasets used for training, validation and tests is summarized in Table 1. Model architecture In this study we opted for a fully connected feed-forward network based on

• the trained model. Results and Discussion Model classification accuracy Our GlAIcomics model shows a classification accuracy of 100% on the validation set and 99.98% on the test set (S.M : dataset 2 in Table 1). The 8000 synthetic spectra of set 2 were sorted by noise level, amplitude modulation

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• -1121341), the AvH Research Hub project CECANAPROF (3.4-CMR-Hub) and the International Foundation for Science (grant I1-F-6554-1). Author Contributions Conceptualization, S.F.K. and M.S.; methodology, B.Y.G.M., E.G.M.A. and Y.M.-F.; validation, S.F.K. and M.S.; collection of the plant material and

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• intermediate 53 could be obtained in only 8 steps and at a large scale. Validation of this strategy allowed the authors to extend this approach to the total synthesis of alterbrassicicene D (54) and 3(11)-epoxyhypoestenone (55). 1.1.2 Other chemical series possessing a [5-8] unit; 1.1.2.1 Early-stage

Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• . This one might be useful for quantification purposes, provided some validation can be obtained using other appropriate methodologies. A shift of the 1000 cm−1 C–O band towards higher wavenumbers (Supporting Information File 1, Figure S4) occurs for each matrix when going from 100:0 to 0:100 ratio of

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• -like structures and prioritized based on the taxonomic distribution of the cluster. decRiPPter was successfully used for the identification of a new lanthipeptide subfamily, providing experimental validation of the algorithm [65]. A more advanced form of supervised learning is deep learning (Figure 4