Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• ) is depicted as ribbon diagram and the ligands are displayed as stick models (glycoclusters 1 and 2: EE: blue; ZZ: violet; EZ: green; ZE: red). Superposition of the isomers shows the similarity of the binding of the terminal mannoside antenna within the FimH CRD and the different orientations of the

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• products can serve as effective scaffold for the design and synthesis of derivatives with improved biological activities [5][6][7]. Massarilactones are produced by marine and endophytic fungi and bear close biogenetic similarity to several other fungal PKS1-derived metabolites including rosigenin, the

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• products are very appealing biologically relevant scaffolds due to their structural similarity to aminocarboxylic acids [80]. Moreover, the stereochemistry at the phosphorus center is conserved during the reaction. The reaction could also be performed with CH2Br2 and CH2I2 as the C1 building blocks and

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• azobenzenes, spiropyranes and diarylethenes in organic solvents [3][13][15]. There are two strategies of applying diazocines in photopharmacology. The first one exploits the structural similarity of the tricyclic diazocine framework to the tricyclic structure of, e.g., tetrahydrodibenzazocines [16][17] and

• switching properties even in an aqueous environment and are therefore promising switches in photopharmacological applications. a) Structural similarity of N-acetyl diazocine 1 with known 17βHSD3-inhibitor tetrahydrodibenzazocine (THB) [17] and parent diazocine with steroid scaffolds [18]. b) Parent

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

• , screening for particularly stable assemblies [405][411] screens out cages with the taut, dynamic properties found in biological systems [100][146][395][401][412]. Therefore, despite the apparent similarity between porous organic cages (solid state) and robust organic cages (solution state), current leading

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• of 1, an ECD spectrum was measured and compared to a simulated Boltzmann-averaged spectrum (Figure S11, Supporting Information File 1). The similarity factor for each stereoisomer was calculated (Table S1, Supporting Information File 1) [12]. The two diastereomers displaying the highest similarity

• factor between experimental and calculated spectrum are (2’S,3’S,12S) and (2’S,3’S,12R) (Figure 3) differing only at stereocenter C-12. As seen in Figure 3 and Table S1 (Supporting Information File 1), a differentiation between these two diastereomers based on the ECD spectra and similarity factor is not

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• positions. The similarity of the 19F NMR spectra of F and alkoxy-substituted derivatives, Fn, showing 6 single peaks, corresponding to the 8 different fluorine atoms at almost identical positions (Figures S8–S14 and S21 in Supporting Information File 1), confirms that the pattern of the annulation reaction

• F···F repulsion on different rings. G11 exhibits a similar twist between the two triphenylene cores. Further, the calculated HOMO electron cloud of F1 (−5.8 eV; −5.89 eV for PH1) and G11 (−5.60 eV) both are located on a triphenylene core, which explains the similarity of their UV–vis absorption

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• at the para- or meta-position can also induce partial ruffling of the porphyrin core (Table 5). Of all para-functionalized structures, porphyrin 33 bears the most similarity to that of compound 26, with minimal ruffling observed and the overall magnitudes of out-of-plane and in-plane distortions are

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• , 167, and 208 (Figure S4 in Supporting Information File 1). We compared these spectra with those published by Christie et al. on various octadecanoate DMOX derivatives [23][24]. The peak pattern of Bd–Fd showed high similarity to that of the DMOX derivative of 5-enoates. Characteristic ions for

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

• their single-component counterparts. The similarity between these systems made it difficult to assess whether the mixture of gelators resulted in self-sorted or co-assembled fibres using TEM alone. By developing distinct fluorescent probes which could selectively aggregate with, and subsequently stain

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

• reactions is to reference similar chemical reactions using reaction similarity search [174][175] and adopt the reaction conditions used in the literature. ML can leverage the large-scale reaction databases to build global models that can predict reaction conditions for diverse and novel chemical reactions

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

• , since the mechanism of enantioinduction is similar for multiple reactions catalysed by a privileged catalyst class, these ’related’ reactions can in principle be modelled together. The reactions are assumed to be mechanistically transferable. The similarity of multiple reactions led to two different

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

Finding the most potent compounds using active learning on molecular pairs

• Zachary Fralish and
• Daniel Reker

Beilstein J. Org. Chem. 2024, 20, 2152–2162, doi:10.3762/bjoc.20.185

• splits that were generated to mimic real-world medicinal chemistry project data sets [23] such that the external data simulates learning from historic data to predict undiscovered “future” compounds instead of simply being selected from a separate cluster based on chemical similarity (Supporting

• (p = 0.7). To further evaluate the ability of the algorithms to select diverse hits, we evaluated the Tanimoto similarity of their top selected hits compared to their nearest neighbors in the training data. AD-CP selected the molecules least similar to the training set (0.83 ± 0.16, p = 0.0003

• performance for paired approaches. For example, it has been shown that similarity-based pairing during training compound generation for Siamese neural networks can significantly improve model efficiency [36]. Additionally, active learning-based subsampling is an autonomous and adaptive approach that has been

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• artificial systems. Additionally, 5-deazaflavins have emerged as prospective antitumor agents [9][10]. Surprisingly, among the broad family of flavin derivatives, 5-deazaalloxazines have received less attention regarding their photophysical properties, despite their close similarity to the above-mentioned 5

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• demonstrates that increasing the diversity of conjugated cyclic building blocks does not have a notable impact on the relative distribution of molecular shapes. In contrast to their relatively high geometric similarity, the molecular properties of the two datasets vary substantially. We compared the

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

• similarity within the sequences resulting from the BLAST search. Identification and selection of CloA1 and CloA2 BGCs For Clostridia, there were 37 predicted BGCs (15 of these with at least one precursor and one biosynthetic gene, Table S2 in Supporting Information File 1), with 76 precursor peptides

• cluster of C. cellulovorans 743, clostrisin and cellulosin were compared with known lanthipeptides, generating a similarity network made using the percent identity between the precursor peptides from all experimentally characterized lanthipeptides to date (Figure 3A). We found it noteworthy to examine the

• . cellulovurans has directed their evolution to serve completely different biological activities. The amino acid sequence of the precursors shares some similarity with the characterized peptides: for clostrisin with FlvA.2g [42], enterocin Wβ [45], plantaricin Wβ [46], and thusin α [47], and cellulosin with

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

• PoyB and PoyC indicate their high structural similarity with a RMSD of 0.907 Å (552 to 552 atoms) and a sequence similarity of 64.56% (Figure 10). PoyC is the first enzyme in the class B rSAM MTs to perform Cβ-methylations, and exclusive methylates ʟ-configured amino acids. Furthermore, PoyC contains a

• and NMR analysis of the natural product, no knockout studies were performed to identify which enzyme is responsible for the S-methylation. The authors propose LopH as the most likely enzyme, as it shares modest sequence and structural similarity with other MTs. This also hints at a possible new MT

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• linkages in agarose, respectively (Figure 2). However, based on sequence similarity, agarases are alternatively classified into different families of glycoside hydrolases (GHs): GH-96 and GH-117 for α-agarases, and GH-16, GH-50, GH-86, and GH-118 for β-agarases [106]. All agarases characterized from

• structural similarity to two other β-agarases, ZgAgaA and ZgAgaB, from Zobellia galactanivorans, which is a model marine bacterium for the bioconversion of algal biomass [29][107][108][109]. The crystal structure suggested that the thermostability of rAgaA likely derives from the numerous surface salt

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

• value. This is slightly different from our previous approach. However, because of the higher complexity of the reaction and the similarity of aromatic C–H sites, we purposely allow the QM workflow and the ML model to assess more sites as ‘1’ or true site. When the pKa value is within 1.5 pKa units, we

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

• , extended Bemis–Murcko scaffolds were generated by cutting off the side chains of the molecules and retaining ring systems and linkers between them. After removal of duplicates, Tanimoto similarity coefficients were calculated for each pair of the molecules in the compared databases (T = 1 and 0 for similar

• . It was rich in both drug-like and “beyond rule-of-five” compounds and had considerable uniqueness as compared to the available collections (as was shown by Tanimoto similarity and t-distributed stochastic neighbor embedding (t-SNE) comparative analyses). Still, 432 members of the generated chemical

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

• possessed Q at this residue. This substitution can be reasonable, as it serves as a hydrogen bond donor to activate the β-keto moiety of a substrate [31][32]. Additionally, the presence of K (4), which activates the catalytic tyrosine, was more conserved in C2-type KRs. In general, C2-KRs show similarity to

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• diarylhalonium salts in halogen-bonding catalysis [13][14][15][16][17][18][19]. Crabtree has outlined the similarity in molecular orbitals (MO) formed in halogen bonds and hypervalent bonds (and hydrogen bonds) [20]. Recently, we [21], and Legault and Huber [22], independently investigated the connection between

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• functional groups at C6 (Figure 4). The goals were to evaluate the scope of electrophile-mediated cyclization and diversify the gersemiane skeleton for bioactivity assays. A structural similarity search of 5 and 6 revealed that several natural products, including the coral gersemiols [24] and plagicosin N

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• accelerated by enzymes. These enzymes share a similar mechanism of cytosine deamination and a similar tertiary structure. Despite this similarity, individual enzymes are selective for the corresponding cytosine-containing substrates with little or no cross-reactivity. Cytosine deaminase, which is present in