Data accessibility in the chemical sciences: an analysis of recent practice in organic chemistry journals

• Sally Bloodworth,
• Cerys Willoughby and
• Simon J. Coles

Beilstein J. Org. Chem. 2025, 21, 864–876, doi:10.3762/bjoc.21.70

• optionally included. MassBank is a specific repository for small molecule and metabolomics mass spectral data [71][72]. Use open file formats. Where possible, do not provide data in proprietary formats. Become familiar with the data formats and standards in your area of research, IUPAC provide information

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• practitioner takes a piece of paper and imposes a series of folds in order to transform it into an object that has an intricate three-dimensional shape. This concept can also be applied in the molecular world. Starting with a flexible small molecule, a practitioner can impose certain changes to its chemical

• composition such that the new molecule has a better-defined three-dimensional shape. Such “small molecule origami” can offer practical benefits. For example, if a drug molecule is pre-organised into the target-binding conformation, it should exhibit the desirable twin characteristics of high potency (since

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• -natural amino acids are pivotal in protein engineering and drug development. Over 30% of approved small‑molecule drugs today contain non‑canonical amino acid building blocks [1][2]. In peptide and protein engineering, non‑natural amino acids significantly increase the respective range of tools used to

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• cyclic amino acids are common structural motifs in the design of small-molecule drugs and peptidomimetics [1]. For example, the clinically used anesthetics carfentanil (1) and remifentanil (2), the FDA-approved antipruritic medication defelikefalin (3), and the arginase inhibitor 4 [2] possess cyclic α,α

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

• preQ1 congeners into oligonucleotide strands at specific recognition sites. In addition, the potential of modified preQ1 for protein enzyme-independent RNA labeling has also been demonstrated [12][17]. In a recent study [4], sequence-specific RNA–small molecule crosslinking (Scheme 1B) was achieved in

• highly electrophilic warheads otherwise typically employed in RNA-small molecule crosslinking [18][19][20][21]. Instead, primary alkyl halides (or mesylates, Scheme 1, in particular compounds 3a, 3b and 4c) were found to be potent yet mild alkylators that minimize off-target reactivity, while providing

• reasonably fast labeling kinetics and up to quantitative conversion under quasi-physiological conditions [4]. Obviously, the rapid dissemination and widespread acceptance of such labeling methods depend on fast and simple access to the small molecule probes. Here, we report efficient synthetic routes to

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

• chimera (PROTAC) has made it a popular starting point to develop selective small-molecule degraders [2]. Currently, leveraging ubiquitination by the von Hippel–Lindau (VHL) protein or cereblon (CRBN) is the most successful method to achieve targeted protein degradation [3][4]. For initial studies, a short

• iVeliparib-AP6. As a common practice for small-molecule library synthesis, the identity and the purity of the reaction products of this simple, 3-step process were analyzed by LC–MS. Whereas the HPLC traces of the reaction mixtures showed one major product peak, the final product carried a barely noticeable

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

• literature in other areas relevant to the application of ML to chemical synthesis that are not covered by our review, such as small molecule discovery [8], drug discovery [9][10], retrosynthesis [11][12], and catalyst selection and design [13][14]. Review HTE platforms HTE platforms were designed to

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• activity of biologically relevant molecules [22], and compounds containing fluorine have seen huge success in medicine and agrochemicals, with over 30% of small molecule drugs [23][24] and 16% of pesticides [25] now containing fluorine atoms. A range of synthetically important fluorinated hetero- and

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

• corresponding nucleic acid sequence. Proteinaceous enzymes then go on to catalyze biosynthetic reactions that put together small molecule building blocks (BB) to generate natural products with extremely diverse chemical structures. Because the intricacy of this process is not fully understood, scientists still

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• maintaining a structural control that is as high as that in the small-molecule system, where complicated synthesis is more accepted. Employing cyclodextrin (CD) as a ring unit represents a reasonable option for reducing the synthetic cost because of its lower production cost compared with those of other

• typical ring molecules [31][32][33][34][35]. Meanwhile, the studies on CD-based rotaxane are generally divided into two aspects: (1) the construction of a complicated small-molecule framework and the evaluation of its properties, and (2) the development of a polymer material (e.g., polyrotaxane) with a

• rough structural control. Ideally, the accurate control of the structure of a small-molecule system is directly transferred to the corresponding polymer framework to implement a defined rotaxane structure on the latter for precise property control, although an existing huge gap between the studies on

The charge transport properties of dicyanomethylene-functionalised violanthrone derivatives

• Sondos A. J. Almahmoud,
• Joseph Cameron,
• Dylan Wilkinson,
• Michele Cariello,
• Claire Wilson,
• Alan A. Wiles,
• Peter J. Skabara and
• Graeme Cooke

Beilstein J. Org. Chem. 2024, 20, 2921–2930, doi:10.3762/bjoc.20.244

• , Glasgow, G12 8QQ, UK 10.3762/bjoc.20.244 Abstract The study of organic small molecule semiconductor materials as active components of organic electronic devices continues to attract considerable attention due to the range of advantages these molecules can offer. Here, we report the synthesis of three

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• (small-molecule concept) offer a distinctive advantage in the synthesis of new biologically active molecules, as they are synthetic bioisosters of purine bases. Imidazo[1,2-a]pyrimidine derivatives exhibit a wide range of pharmacological properties [4][5][6]. For example, this scaffold is a key

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

• study several small molecule probes were used including propargylamine, a glutamine derivative, N6-propargyladenosine and a tyrosine derivative to document the thiotriazole formation during CuAAC. The two selected examples of adenosine and glutamine-derived diagnostic ions are shown in Figure 8E. Since

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

• docking refinement algorithm integrated in the RosettaCarbohydrate framework [135], allowed the use of Rosetta macromolecular modelling and design software suite to perform docking calculations on glycans bound to proteins with a higher accuracy with respect to previous Rosetta’s protein−small molecule

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

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• ; fluorobenziodoxoles; halogen bonding; hypervalent iodine; Selectfluor; Introduction An important strategy in the drug discovery process is the incorporation of fluorine into biologically active molecules because fluorine can improve bioactivity and pharmacokinetic properties [1]. Consequently, 22% of all small

• -molecule drugs contain at least one fluorine atom [2]. Hypervalent iodine(III) fluorides, such as difluoroiodotoluene 1 and fluoroiodane 2, have been key to the development of numerous, new synthetic procedures for C–F bond formation over the last decade. Since difluoroiodotoluene 1 has low chemical

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• discussion will also encompass the design of biosynthetic intermediates and their analogs to achieve chemo-enzymatic total syntheses. Given our emphasis on natural products, this review does not cover the exquisite synthetic approaches involving biocatalysts for small-molecule pharmaceuticals. To gain a more

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

• pathways Methyltransferases can be classified based on various factors, such as their substrates (small molecule MTs, protein MTs, or RNA/DNA MTs), the atom that accepts the methyl group (oxygen = O-MTs, nitrogen = N-MTs, carbon = C-MTs, sulphur = S-MTs, or halide = H-MTs), metal or cofactor dependence

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• candidate precursor peptide and observation of a corresponding small molecule are unclear. For example, precursors rich in S/TxY core motifs are prevalent in nature, but do not correspond to a known molecule [7]. Therefore, we sought to rapidly identify the most promising candidates. This presented a

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• ; organocatalysis; pyrazoles; Introduction N-Heterocycles are attractive molecules owing to their extensive applications in small-molecule drugs, natural products, and agrochemical products [1][2][3]. Among the N-heterocycles, pyrazole is an important structural scaffold, found in several marketed drugs and

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• addition, the compatibility of the method with solid-phase synthesis is shown exemplarily. Keywords: azide; click reaction; CuAAC; pyrazole; triazene; triazole; Introduction Nitrogen-containing heterocycles are central scaffolds in medicinal chemistry and are incorporated in most small-molecule drugs [1

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• [8][9]. In the last few years we have been active in isatin modification using new synthetic approaches, anticipating the creation of new libraries of small-molecule hybrids with potential as cholinesterase inhibitors [10][11][12][13], important to treat neurodegenerative diseases, and anticancer

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

• multiple opportunities for various further chemical manipulations which may allow the discovery of novel bioactive small molecule tools. Recently, the fragment-based drug discovery (FBDD) approach has been emerged as a promising starting point for the new drug discovery, which typically involves the

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• groups, using a ribosome engineering approach in Streptomyces sp. CB02009 (Figure 2d) [48]. Seyedsayamdost et al. developed the high-throughput elicitor screening (HiTES) approach, a forward chemical genetics method that identifies small-molecule inducers of silent natural products (Figure 2e) [49]. Han

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• with emphasis on the structural diversity of small-molecule ligands. In this context, acyl-acyl carrier protein (acyl-ACP) thioesterase inhibitors have shown a remarkable variability. Fatty acid thioesterase (FAT) enzymes represent a family of proteins exclusively found in higher plants. They mediate