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

• -orientation of one glycoligand in the presence of another glycoligand that remains unaffected. It seems to be obvious that an “optoglycomics” approach in the glycosciences in order to investigate carbohydrate function by light can lead to new insights into carbohydrate recognition. However, complex systems

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

• cyclic amines. Next, we will examine some important derivatives of amines, such as amides and sulfonamides. Throughout, the emphasis will mostly be on bioactive molecules, but finally this section will conclude by examining a different type of molecular function, namely, organocatalysis. When fluorine is

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

• , interaction and function. Furthermore, the synthesis of both isomers of trifluoroleucine was described. (2S,4R)-Trifluoroleucine could be isolated on a milligram-scale in good yields and excellent enantiomeric purities, representing a viable synthetic route for these building blocks adding another strategy to

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• function. Their chemical modification has been developed using iminoxyl radicals [28]. Although numerous methods exist for the functionalization of Trp in proteins, their application in the elaboration of ADCs is limited [29]. Given the many challenges in antibody modification as outlined above, it is

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

• cytotoxic activity of natural products by increasing the hydrophobicity, enhancing cell membrane permeability and binding affinity with intracellular targets [26]. Structure–activity relationships analysis of both hemisynthetic products 2 and 3 revealed a shared conjugated methylene olefinic function that

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

• function as aldehyde equivalent in reactions where iminium species are involved. In this case, the C–X bond of the dihaloalkanes can be activated by metal catalysis, allowing the incorporation of the C1 building block by a mechanism that does not involve the preformation of an imine/enamine intermediate

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

• , normalized against the resonance for residual CHCl3, was monitored as a function of irradiation time. The results are shown in Supporting Information File 1, Table S1. These same sets of experimental conditions were applied to a sample of ANTH. A gradual decrease in the % remaining of both ANTH and 9,10-ANTH

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• , since in a control experiment without RFTA the mixture was found to liquefy. This was due to the heat generated by LEDs and not by the grinding action. Thus, light irradiation fulfils a double function: the excitation of the photocatalyst and melting of the substrate, inducing mobility of the molecules

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

• with clear thermodynamic minima [410]. Although this approach might be forward-thinking in terms of materials access, cost, and scale, without precise property prediction it requires serendipity in terms of function-discovery within a “near infinite design space” [376]. Further, by definition

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

• Bingnan Wang Yong Lu Chuo Chen Department of Biochemistry, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA 10.3762/bjoc.21.28 Abstract Chemically induced dimerization is a powerful tool for studying protein function, wherein the IMiD (the “immunomodulatory

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• IR spectra of compounds 5a–6d containing an alkoxyfuropyran fragment shows that in the case of methyl esters 5a, 6a, and 6c the absorption band of the alkoxycarbonyl function is shifted to a lower frequency region (1714–1721 cm−1), while ethyl esters 5b, 6b, and 6d are characterized by higher

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• reaction yields as a function of the reaction-scale. As this latter increases, the obtained yields using [Ru(bpy)3]2+ under blue light decrease significantly to reach a yield loss of 31.6% at a 250× scale, while those using [Os(tpy)2]2+ under near-infrared light remain constant or even increase up to a

• systems can function as both photooxidants and photoreductants, engaging in either energy-transfer or electron-transfer processes with high efficiency [40]. Notably, D. Gryko et al. demonstrated their application in activating diazoalkanes through red-light-mediated photosensitization and photoredox

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• polymers (Scheme 1). The terpyridyl group and the pyridinium cation in the AB-type monomer G2 each function as a “sticker” to enable supramolecular polymerization in the presence of the macrocyclic component and zinc ions. The driving force for the recognition involves multiple cooperative interactions

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

• , the HTE can function as a self-driving platform where the next iteration of experiments is automatically selected by algorithm without human intervention. This section will highlight the key features of various HTE platforms, including benefits, limitations, and applications to organic molecule

• functions. These models learned the relationships between the reaction conditions and the target optimization objectives based on experimental data. In a second step, these models are efficiently probed to identify the most promising values for optimizing the objective function. In this section, we review

• objective function. In multiobjective optimizations, the algorithms will search for optimal conditions that either maximize or minimize each objective function. On the other hand, when competing objectives are optimized, the algorithm aims to discover the set of solutions where the improvement of one

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

• biology are facile and quantitative. But they do not tell us the function of a particular glycoform on a specific glycoprotein. To put glycans on the map, chemists needed to be inventive. At the time of writing this Editorial article, we are all early- and mid-career investigators who have learned from

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• recently showed that polymerizing negatively curved polycyclic arenes produced an amorphous covalent network. This network was able to mimic the structure and function of carbon schwarzites, serving as an anode material in lithium-ion batteries with high capacity [21]. Further exploration of bottom-up

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• the ester function, as previously reported [32][33][34][35]. The corresponding adducts 5a–f were isolated with good yields from 66 to 88%. In the case of hydrazides 5e and 5f, the mixture of diastereomers (1:1 ratio) could not be separated at this stage. Although no stereoselectivity is observed, it

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

• stress (OS) [25]. Alzheimer’s disease (AD) is commonly thought to emerge from a deficiency of the neurotransmitter acetylcholine (ACh) in neuronal and neuromuscular regions, according to the most recognized theory. This deficit may be caused by reduced synthesis or enzymatic function of

• benzodioxepinones 12 in all cases (Scheme 11). The synthesized compounds demonstrated excellent drug-like features. Parkinson disease (PD) Knoevenagel–Michael addition/cyclization (MCR 3 + 2): Sirtuins, a group of enzymes that rely on NAD+ to function as protein deacetylases, have garnered attention across multiple

• areas, including lifespan extension, obesity, age-associated diseases, neurological function, cardiovascular disorders, and cancer. Notably, the inhibition of sirtuin 2 (SIRT2) has demonstrated protective effects in both primary neuronal cultures and invertebrate models of PD [48]. SIRT2 is present in

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• bicyclopentyl radical philicities. In addition, we demonstrate that similar reaction conditions can be applied to the synthesis of the analogous CF3SF4-containing [2]staffane (CF3SF4-BCP-BCP-Cl, 3). Finally, we examined compound 3 by SC-XRD and found that it undergoes a phase transition as a function of rate of

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• that function as hydrogen-bond donors and acceptors. Additionally, the nitrogen atoms in the pyrrole units of the porphyrin structure can also act as Lewis bases, capable of donating electron pairs. These properties enable tetrapyrrolic macrocycles to act as effective binding sites or catalytically

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

• approaches to enable broader exploration New approaches have been developed to circumvent the aforementioned constraints and enable the exploration of a broader natural product chemical space. Existing approaches fall into two broad categories – sequence metagenomics (Figure 2a) and function metagenomics

• (Figure 2b). The former analyzes nucleic acid sequences to prioritize BGCs that are worth exploring [20]. For example, it has been shown that tracking characteristic biosynthetic or self-resistance gene(s) can facilitate the discovery of new congeners of a natural product family [21][22]. Function

• morphology of the host, etc. [25]. Sequence and function metagenomic approaches have been reviewed elsewhere and will not be covered herein [26][27][28]. This Perspective focuses on chemical structure metagenomics (Figure 2c), an emerging field that integrates bioinformatics, chemical synthesis, molecular

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

• in a high yield. In this reaction, the size of the end-capping agent is the key, as an extremely large reagent does not react well with the amino axle-end groups, whereas an extremely small reagent cannot function as an end-cap. This reaction exhibits the following multiple advantages compared with

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• ,1H-NOESY spectrum of compound 1c in DMSO-d6. Absorption (left) and normalized emission spectra (right) of compound 1i in various solvents (c = 10−5 M). Solvatochromic behavior of compounds 1c and 1i: plots of arithmetic mean of emission/absorption wavenumbers vs Kawsk–Chamma–Viallet polarity function

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• carried out as part of the investigation of the enzymatic function of cytochrome P-450 with low valent ruthenium complex catalysts. Various phenols 86 bearing para-substituents were transformed into the corresponding tert-butyldioxy dienones 87 smoothly using RuCl2(PPh3)3 as the catalyst (Scheme 31) [83

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• , see Scheme 1). In order to break the symmetry and to generate the acid function only on one side, benzyl protection was performed. From diols 1, 2, and 3 statistical mixtures of unprotected, mono-, and di-protected products were obtained, from which the isolation of the desired mono-protected products