Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• biosynthetic pathway for brassicicenes, which share the same carbon skeleton and similar oxidation and unsaturation states as cotylenol and cotylenin A [36]. In a previous study, Oikawa and co-workers reported the identification of brassicicene BGC in Pseudocercospora fijiensis [37]. By heterologous expression

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• Compact Data Analyst (Bruker software) to provide accurate and high-resolution mass per charge of molecular ions in the sample and generate molecular formulae using a Bruker Smart Formula manually. Microbial isolation and identification The Pseudomonas sp. UIAU-6B strain was isolated from a sediment

• sample collected off the heavy metal-contaminated Oyun River in Nigeria. The isolation and identification of the bacterial strain UIAU-6B has been previously reported [15]. Small-scale culture Pure colonies of the Pseudomonas sp. UIAU-6B were inoculated into 100 mL of SGG (10 g of glucose, 10 g of

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• , known entities and they were identified based on their high-resolution mass spectra. The mass spectrometric identification and purity determination of the products have been carried out by using an Agilent 7250 GC-QTOF mass spectrometer operated in electron impact ionization (EI, 70 eV) mode using a 30m

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• well-established that it is featured in nearly every organic chemistry textbook. However, despite their versatility, enamines themselves are not easily handling compounds in experimental settings. Their sensitivity to hydrolysis complicates their isolation and identification, and following the

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• diverse scaffolds have been reported in the literature, the identification and use of novel PCs with tunable and diverse optical and redox properties can pave the way to uncharted reactivity. In this context, sulfur-based cores, widely used as acceptors in photoelectric materials [9][10][11][12][13][14

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• (C8F17)2 [36]. These results make it clear that monitoring photoirradiated solutions by UV–vis spectroscopy must be accompanied by complementary analyses to enable accurate interpretation of the changes in the UV–vis spectra and identification of the photoproducts. The next comparative photostability

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

• biotechnological applications, including the identification of queuosinylation sites in cellular RNA [13], RNA and DNA labeling [14][15], and mRNA photocaging [16]. The latter applications rely on the promiscuity of the tRNA-modifying enzyme tRNA-guanine transglycosylase (TGT), which can incorporate functionalized

• 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

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

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

• exploiting emergent geometric rules and post-assembly modifications; (3) improved screening and collection of detailed structure–activity-relationship (SAR) data for modular systems to allow systematic design, rational and computational development, and identification of novel activity. These developments

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• drug”) class of PROTAC molecules with a PEG linker is frequently used to promote targeted protein degradation. The standard protocol for their synthesis involves nucleophilic aromatic substitution of 4-fluorothalidomide with a PEG-amine. We report herein the identification of a commonly ignored

• sulfonate to the byproduct by reacting it with taurine allows for easy decontamination. This method may facilitate the purification of other similar reactions and improve the quality of related pomalidomide derivatives. The structures of veliparib and iVeliparib-AP6. Identification of the cryptic impurity

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

• with feedback DOE facilitated the rapid identification of appropriate solvents. Notably, the use of DMSO, DMF, and pyridine led to an enhanced yield of the monoalkylated product. An experimental setup was developed for single-droplet studies of visible-light photoredox catalysis using an oscillatory

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• ], therefore it is no surprise that sponges are highly sought after for novel bioactive metabolites and have been a major focus of marine natural product drug discovery for over 70 years. The identification of ianthelliformisamines A–C from the Australian marine sponge Suberea ianthelliformis, which displayed

• available [16] but neither of these compounds has been fully characterised with only the total synthesis of 7 being reported in the literature [8]. Our study reports the first identification of 6 and 7 from a natural origin and the first full characterisation of these molecules using NMR, UV, and MS data

• commercially available primary amine, 1-(3-aminopropyl)pyrrolidin-2-one completed the total synthesis of the natural product in an overall yield of 1.5%. The NMR data comparison of the natural product and our synthetic compound was essentially identical. Due to our interest in the identification of potential

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• makes them invaluable in accelerating drug discovery processes. The synergy between multicomponent chemistry and medicinal chemistry offers a highly attractive and competitive approach to accelerate drug discovery and development, facilitating the identification and the optimization of novel therapeutic

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• would be fractionated further, tested again, and this process would be performed iteratively until a pure compound is obtained. Notably, BGF is not limited to the identification of metabolites with antimicrobial activity or those of bacterial origin. It is applicable to the screening of natural products

• failed to match a nonribosomal code in the algorithm training dataset and were deemed “unpredictable” [37]. It is also possible that the A domain in question aligned so poorly to prototypical A domains that prevented the proper identification of the nonribosomal code itself [70]. Regardless of the

• . Fractionation is an iterative process guided by screening for the desired bioactivity until the isolation of a pure compound. This workflow was invented by Selman Waksman and has facilitated the identification of the vast majority of natural products known to date. However, it has fallen out of favor due to

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• fluoride ion, respectively. Volcanic 1.3.3, a Python package for the NaviCat platform, was used to generate 3D volcano plots, facilitating the identification of the most appropriate catalyst for the coupling reaction being considered [27]. Volcano plots Volcano plots are a visualisation of the Sabatier

• –CH(CH3) bond. Additionally, the (S)-epoxide enantiomer was employed consistently. Symmetric FLP scaffolds – achiral environment Following the initial exploration and preliminary results, our attention shifted toward the identification of a suitable catalyst. Drawing inspiration from the literature

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

• , proline-containing diketopiperazines were identified for the first time in snake scent glands, although an artificial formation from amino acids likely present in the secretion cannot be excluded. Keywords: carboxylic acids; identification; mass spectrometry; pheromones; snakes; Introduction Located in

• components of the SGS bouquet obtained from animals living in a zoo, including the identification of unique fatty acids of medium chain length not reported before from nature. Similar acids are not known from any other snake. In addition, small amounts of diketopiperazines were found for the first time in

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

• cavity (b) and in the center of the upper rim plane. Therefore, the narrow rim with the H-bonded primary OH groups can be considered as a major attractor (anchor, hot spot) for the incoming water molecules. The identification of this hot spot location provides very useful information for modelling the γ

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

• Andreas Wiest Pavel Kielkowski LMU Munich, Department of Chemistry, Butenandtstr. 5-13, 81377 Munich, Germany 10.3762/bjoc.20.199 Abstract Identification of interactions between proteins and natural products or similar active small molecules is crucial for understanding of their mechanism of

• identification rates and may help to identify otherwise difficult to find interactions between active compounds and proteins, which may result from unperturbed conditions, and thus are of high physiological relevance. Keywords: chemical proteomics; diagnostic ions; mass spectrometry; target identification

• disease [2][3]. In parallel, mass spectrometry (MS) has been crucial in many areas centered around the characterization of NPs [4]. First to annotate their often complex structures using diverse fragmentation techniques [4]. Nowadays, MS is applied for the identification of NPs’ cellular protein targets

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

• , balancing high enantioselectivity with a broader substrate scope. CSC enabled the identification of two well-performing, general catalysts. A different generality metric was proposed by Betinol et al. [133] (Figure 13). The authors performed clustering on the reaction space of interest representing the

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

• exhibit poor performance during early project stages where the training data is limited and model exploitation might lead to analog identification with limited scaffold diversity. Here, we present ActiveDelta, an adaptive approach that leverages paired molecular representations to predict improvements

• regimes by enabling faster and more accurate identification of more diverse molecular hits against critical drug targets. Keywords: active learning; drug design; machine learning; molecular optimization; potency predictions; Introduction Active learning is a powerful concept in molecular machine

• learning that allows algorithms to guide iterative experiments to improve model performance and identify the most optimal molecular solutions [1]. Many prominent studies have shown the potential for active learning to accelerate and de-risk the identification of optimal chemical reaction conditions [2][3

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

• physical functions [3]. Glycoscience encompasses the comprehensive study of glycans focusing on their structural, biosynthetic, biological and evolutionary aspects [4], thus playing a central role in the identification and characterisation of the glycome’ structure and function, and in unveiling its

• homology modelling. It guides the user in building protein homology models at different levels of complexity. This program builds a homology model by employing four main steps: (i) identification of structural template(s), (ii) alignment of target sequence and template structure(s), (iii) model-building

• on Voronoi tessellation and alpha spheres. It consists of three main programs: Fpocket for pocket identification, Tpocket for benchmarking pocket detection, and Dpocket for collecting pocket descriptor values. Written in C, Fpocket is well-suited for developing new scoring functions and extracting

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

• ; flow chemistry; Negishi; on-DNA chemistry; Introduction DNA-encoded chemical library (DEL) technology is a powerful tool for hit identification [1][2]. DELs are chemically synthesized libraries in which every member is covalently attached to a unique DNA sequence serving as a molecular “barcode” [3

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

• . Brunschweiger et al. employed the compartmentation strategy to overcome synthetic problems related to the preparation of a DNA-encoded GBB library [17]. DNA-encoded libraries (DELs) are widely used in screening projects, allowing the synthesis of a huge number of compounds as pools, and the identification of

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

• (bottom row) and connected the points in each series by lines to assist in visual identification. The shading represents the 95% confidence interval of the value. Supporting Information The COMPAS-2 dataset is freely available online at the Poranne Group repository: https://gitlab.com/porannegroup/compas

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

• CloPt2, they are Cys18 and His 92. These residues maintained a distance and structural positions like the catalytic residues in PCAT1 (where the catalytic residues are Cys21 and His99). A similar procedure was carried out for CloM1 and CloM2, leading to the identification of the closest sequences within

• Bioinformatic analyses Lanthipeptides identification For the search of lanthipeptides, a LanM class II lanthionine synthetase enzyme gene was selected using a MIBiG [38] search of experimentally characterized lanthipeptide BGCs. 28 LanM enzyme amino acid sequences underwent analysis with BLASTP [39] on the BV