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

• facilitated a site-specific covalent linkage to the antibody, resulting in the formation of a DAR 2 ADC precursor. For their ADC design strategy, the group selected a polyethylene glycol (PEG) linker, as it enhances the water solubility of the ADC, while the payload consists of the cytotoxic agent DM1, which

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

• polyethylene glycol (PEG) linker of various lengths is typically used to build a small library to identify a lead compound. For example, iVeliparib-AP6 (Figure 1) developed through this practice is a PROTAC that degrades poly(ADP-ribose) polymerase 2 (PARP2) selectively [5]. Results and Discussion The

• by which glutarimide displacement affects quality control analysis, we tested a series of amines and compared the retention times of 8 and 9 (Table 1). Rather surprisingly, the length of amino-PEG-OH had no effect on the relative retention time of 8 and 9. The byproduct co-eluted with the desired

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• Remi Peters Levy A. Charleston Karinan van Eck Teun van Berlo Daniela A. Wilson Institute of Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands 10.3762/bjoc.21.5 Abstract Polysarcosine emerges as a promising alternative to polyethylene glycol (PEG

• -polystyrene block copolymers (PEG-PS) stand out for their versatility and adaptability. These copolymers exhibit a remarkable propensity for self-assembly, allowing the formation of vesicles capable of undergoing diverse shape transformations. Notably, they can adopt the distinctive stomatocyte morphology

• , characterized by a concave shape with a central cavity [1]. Such structures hold significant potential for drug delivery applications as nanomotors, offering both encapsulation capability and controlled release functionalities [2][3]. Moreover, researchers have explored novel shapes utilizing PEG-PS copolymers

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

• generally comprises a linear polymer-chain-like polyethylene glycol (PEG) and many rings, the loss of a few rings at the end-capping step is not expected to cause a severe issue during polyrotaxane synthesis, as applicable in small-rotaxane-molecule synthesis. Harada and Kamachi first synthesized

• pseudopolyrotaxane by simply mixing α-CD and PEG in water [40]. In this reaction, all the components were soluble in water, although the product did not dissolve. This indicated that pseudopolyrotaxane could be collected by the simple filtration of the reaction mixture. This pseudopolyrotaxane synthesis also

• depended on the cavity size, the same as small-molecule inclusion. For example, PEG forms stable pseudopolyrotaxane structures with α, β, and γ-CDs, although polypropylene glycol (PPG) only forms a stable pseudopolyrotaxane structure with β-CD [41]. In addition to these linear polymer chains, various types

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

• large tag, which significantly changes the molecular weight of the given protein. The shift on the gel can be then visualized by protein-specific antibody or coomassie staining. The linkers applied to perform the gel shift assay contain a linear PEG polymer with an approximate size ranging from one to

• dozens of kilodaltons. The main advantage of the gel shift assay is to obtain quantitative information of the protein’s probe modification extent, considering high efficiency of the click reaction. Given the bulkiness of the PEG–azide linker, the bioorthogonal reaction needs some optimization, including

• presence of the PEG moiety, which has likely only minimal influence on the diagnostic peaks’ generation. Taken together, consideration of the oxonium-biotin and dehydrobiotin diagnostic ions increases the confidence in the identified probe–peptide conjugates. Next, selective elution of the probe–peptide

Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• encoding for the target protein, amino acids and nucleoside triphosphates as substrates, an energy regeneration system and other additives such as polyethylene glycol (PEG) [9]. Although CFPS has been used and improved since the 1960s, there are challenges in its application such as low production volumes

• influence on the synthesis performance of CFPS. Polymers, DES, and organic solvents were considered to modify the fluid properties. Polymers and deep eutectic solvents (DES) as additives in CFPS Polymers (PEG, methylcellulose (MC), and carboxymethylcellulose (CMC)) and DES (choline chloride/urea, betaine

• lower viscosity than that of the E. coli cytoplasm [25]. The amount of macromolecules in the CFPS system is 167–265 g/L, only slightly less than in a living cell. The calculation is based on the estimated concentrations of macromolecules in the cell extract, tRNA, plasmid, and PEG. Although the

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• ). Firstly, we chose NaOH to optimize the reaction conditions. Apparently, in the absence of a solubilizer, no reaction occurred due to poor solubility of 1a in boiling water (Table 1, entry 6). Macrogol 400 (PEG-400) is emerging as an environmentally friendly nonionic solubilizer due to its unique merits

• , such as nontoxicity, inexpensiveness, nonflammability, low volatility and good water solubility, which are consistent with the concept of green chemistry [74][75]. Therefore, we tested the reaction in the presence of PEG-400 (Table 1, entries 7–9). It was found that the reaction uniquely produced 3a in

• 48% yield when using 3.0 equiv of PEG-400 as solubilizer (Table 1, entry 8), and further increasing the PEG-400 loading could not remarkably improve the yield of 3a (Table 1, entry 9). With this in mind, we selected 3.0 equiv of PEG-400 as solubilizer in our study. Next, we examined the influence of

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• -pot process can be conducted in various solvents such as in PEG 400 [79], ionic liquids like 1-butyl-3-methylimidazolium hydroxide ((Bim)OH) [80], the nanoionic liquid 1-methylimidazolium trinitrocarbide ([[HMIM]C(NO2)3]) [81], N-methylpyridinium tosylate (NMPYT) [82], or glucose-based strong eutectic

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• achieved. Product 21 could be resubjected to the reaction conditions, affording difluoride 22 in 46% yield. Metal fluorides are an economical source of nucleophilic fluorine, but are sparingly soluble in organic solvents. To overcome this, in 2012, Fuchigami and co-workers used polyethylene glycol (PEG) to

• dissolve caesium fluorides and facilitate an electrochemical benzylic C(sp3)–H fluorination of triphenylmethane (Figure 39) [97]. The authors suggested that PEG complexed the metal ion, increasing the nucleophilicity of the fluoride ion. Product 23 was achieved in 85% isolated yield after a small

• PEG and CsF. Electrochemical benzylic C(sp3)–H fluorination with caesium fluoride and fluorinated alcohol HFIP. Electrochemical secondary and tertiary benzylic C(sp3)–H fluorination. GF = graphite felt. DCE = 1,2-dichloroethane. Electrochemical primary benzylic C(sp3)–H fluorination of electron-poor

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• -soluble C60 and C70 derivatives by covalently attaching biocompatible water-soluble polymers, such as polyethylene glycol (PEG) [37][38] and PVP [39]. Although these C60– and C70–polymer conjugates revealed high water-solubility, it was found that they, especially the PEG conjugates, formed micelle-like

• C60–peptide conjugates in this study. In addition to the water solubility introduced by the peptides, these conjugates have a superior biocompatibility compared to those with synthetic polymers, such as PEG and PVP. We utilized the previously reported biscarboxylic acid derivative 3, which was

• a similar peptide (GABA-(Lys)5-peptide-PEG) on resin for the reaction with compound 3. Initial trials, using 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and N-methylmorpholine (NMM), respectively, as a coupling reagent and a base, and 5 equiv of peptide on

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• catalytic arrangements of the most enantioselective catalysts, including anchoring on polystyrene beads [8][9], magnetic nanoparticles [10], or block copolymers composed of PEG-poly(Glu) [11]. These modifications have facilitated the recycling of the catalysts, offering numerous advantages, including

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• Fe3O4@PEG-SO3H complex were added in ethanol for a time period of 5 to 10 minutes, yielding 88–98% of isolated product with only aromatic aldehydes showing a meaningful reactivity (Scheme 23) [122]. In 2022, Boroujeni et al. employed a Cu(II) complex coated in Fe3O4@SiO2 nanoparticles which worked as an

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

• ), did not give rise to any diffraction. Multiple layer plate or needles clusters were obtained in the presence of PEGs, but only showed weak diffraction (≈3.5 Å). Finally, in the presence of 20% PEG 8K, 0.2 M MgCl2, and 0.1 M Tris HCl pH 8.5, single diamond-shaped crystals were obtained after 1–2 days

• were used and led to more than 30 hits after one to three days. Pill-like crystals were obtained with high salt concentration that could be reproduced by hand in the laboratory. Plates and needles clusters were obtained with PEG containing solutions. For CMA1-Nter, protein at a concentration of 2.9–3.5

• mg/mL was crystallized using hanging drop and vapor diffusion methods with a 2 µL drop in 1:1 ratio at 20 °C. Bipyramidal single crystals were obtained after one or two days in a solution containing 10–12% PEG Smear Medium, 0.1 M MES pH 6.5, 1× divalent (5 mM of CaCl2, MgCl2, CsCl2, CdCl2, NiCl2, and

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• synthesis of N-substituted pyrroles 29 in the yields of 85–97% using squaric acid as catalyst. In this reaction, various amines 28 and 2,5-DMTHF (2) were reacted in greener solvents like water, deep eutectic solvent (DEC) and polyethylene glycol (PEG) under thermal or ultrasonic irradiation (Scheme 13a

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• biomedical applications, in particular as an alternative to the hydrophilic poly(ethylene glycol) (PEG), which is the polymer of choice for many biomedical applications due to its high solubility, low cytotoxicity and biocompatibility [3][4][5][6][7][8][9]. However, an ongoing discussion about pre-existing

• K. HFIP was supplemented with 3 g/L potassium triflate, and the flow rate was adjusted to 0.50 mL/min. Calibration was performed using PEG standards with molar masses ranging from 0.1–1,000 kg/mol. Before every measurement, samples were filtered through 0.2 µm PTFE filters, Roth (Karlsruhe, Germany

• typically set from 1000 m/z to 7000 m/z. After parameter optimization, the instrument was calibrated with PEG standards depending on the m/z range of the individual sample. Samples were prepared with sinapinic acid (3,5-dimethoxy-4-hydroxycinnamic acid, SA) as matrices using the dried-droplet spotting

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• interactions [5][6][7]. For example, a binding curve generated for the interaction between an RGD-peptide (C-PEG6-GGRGDGP) and its integrin (α5,β1) target is shown in Figure 4 below. A PEG-linker was added to the RGD-peptide so that the peptide would not be buried in the polymer coating the surface of the

• array, a scenario that would make it unavailable for binding to the integrin receptor in the subsequent analytical experiment. The PEG-6-linker was selected because it was effective and readily available from commercial sources. This linker was functionalized with a cysteine on the end opposite the

• peptides were placed on the array along with a fluorescent dye (LRSC, lissamine rhodamine) that was used to make sure the placement chemistry was working. The array used was coated with the borate ester diblock copolymer (Figure 2), and the peptides were attached to this polymer through a PEG-6 linker in

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• for the halogenation of organic substrates. For example, Banerjee and co-workers reported the mono-, di-, and trihalogenation of aromatics by controlling the stoichiometry of the N-halosuccinimide (NXS) and PEG-400 as the grinding auxiliary in a mechanical grinder (Scheme 1a) [3]. N-Halosuccinimides

• José G. Hernández Bochum, Medellín, October 2022 ORCID® iDs Lars Borchardt - https://orcid.org/0000-0002-8778-7816 José G. Hernández - https://orcid.org/0000-0001-9064-4456 a) Mechanochemical PEG-400-assisted halogenation of phenols and anilines using NXS. b) Halogenation of azobenzenes with NXS

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• catalyst-free halogenation of phenols and anilines via liquid-assisted grinding using PEG-400 as the grinding auxiliary. A series of mono-, di-, and tri-halogenated phenols and anilines was synthesized in good to excellent yields within 10–15 min in a chemoselective manner by controlling the stoichiometry

• of N-halosuccinimides (NXS, X = Br, I, and Cl). It was observed that PEG-400 plays a key role in controlling the reactivity of the substrates and to afford better regioselectivity. Almost exclusive para-selectivity was observed for the aromatic substrates with free o- and p-positions for mono- and

• reaction time, and mild reaction conditions are a few noticeable merits of this environmentally sustainable mechanochemical protocol. Keywords: automated grinding; chemoselectivity; mechanochemistry; N-bromosuccinimide; PEG-400; regioselectivity; stoichiometry-controlled halogenation; Introduction Aryl

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• materials to inductively heat up glass reactors. For the Biginelli reaction solubility of the starting urea (22) as well as the products 24a and 24b were an issue being overcome by using a solvent mixture of PEG/DMF 1:1. Also the proline-catalyzed asymmetric Mannich reaction was achieved with cyclohexanone

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• , Saugus, MA, USA). The DART ion source was operated with helium gas (approximately 4.0 L/min flow rate), the gas heater (350 °C), and the source grid (350 V). The data acquisition range was from m/z 50 to 1000. Polyethylene glycol (PEG 600) was used for the exact mass calibration. General synthetic

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• catalysis. The catalytic activity of Co@imine-POP was investigated in a Sonogashira coupling of bromobenzene and phenylacetylene under different reaction conditions. The optimized reaction conditions were found to be 1.7 mol % of the Co@imine-POP catalyst, PEG as solvent and 80 °C reaction temperature

• , recyclable, and selective for the coupling between aryl halides and phenylacetylene in PEG as the solvent (Scheme 22). The effect of various reaction parameters such as solvent, base, temperature, and catalyst loading was assessed by the model reaction between bromobenzene and phenylacetylene. Optimization

• studies revealed PEG-200 and K3PO4 as suitable solvent and base, respectively. Aryl halides with electron-donating and electron-withdrawing groups afforded the corresponding products in good yields with 0.15 mmol of catalyst in PEG at 60 °C. A three-component coupling of alkyne with a heterogeneous

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• bond from β-NQS. Method A: NaOH, EtOH/H2O, 40 °C, 2 h; Method B: t-BuOK, PEG-300, rt, 6–10 min. C=C bond formation from β-NQS and substituted acetonitriles. Funding Fellowships granted by CNPq (301873/2019-4 and 306011/2020-4), CAPES (Financial Code 001), and FAPERJ (E-26/203.191/2017, E-26/202.800

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• synthesis of monodisperse polyethylene glycols (PEGs) and their derivatives usually involves using an acid-labile protecting group such as DMTr and coupling the two PEG moieties together under basic Williamson ether formation conditions. Using this approach, each elongation of PEG is achieved in three steps

• – deprotection, deprotonation and coupling – in two pots. Here, we report a more convenient approach for PEG synthesis featuring the use of a base-labile protecting group such as the phenethyl group. Using this approach, each elongation of PEG can be achieved in two steps – deprotection and coupling – in only

• one pot. The deprotonation step, and the isolation and purification of the intermediate product after deprotection using existing approaches are no longer needed when the one-pot approach is used. Because the stepwise PEG synthesis usually requires multiple PEG elongation cycles, the new PEG synthesis

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• hydrogels could also be adjusted by varying the ratio of CBMA to GelMA which gives it a high degree of customisability. The use of cryogels in neuroscience applications is gaining interest due to their soft and spongey properties [80]. Newland et al. recently reported on the use of injectable PEG/heparin

In-depth characterization of self-healing polymers based on π–π interactions

• Josefine Meurer,
• Julian Hniopek,
• Johannes Ahner,
• Michael Schmitt,
• Jürgen Popp,
• Stefan Zechel,
• Kalina Peneva and
• Martin D. Hager

Beilstein J. Org. Chem. 2021, 17, 2496–2504, doi:10.3762/bjoc.17.166

• masses. Subsequently, both polymers were characterized regarding their structure. For this purpose, size exclusion chromatography (SEC) was performed revealing a molar mass of Mn = 11,400 g/mol for P1 and Mn = 17,400 g/mol for P2 with respect to a PEG-standard. The SEC traces of both polymers are

• reported in literature [23]. During cooling, the reformation of the perylene domain was also observed. Finally, P2 featured a second endothermic transition at 13 °C, which is based on the melting of the short PEG-block [24]. Furthermore, both polymers were characterized via rheology and dynamic mechanical

• second phase transition of the PEG moieties observed in the DSC. Nevertheless, at 150 °C, P2 also shows the clear broadening of bands, which is consistent with the very similar positions for the perylene π–π interaction signal in the DSC. All these findings clearly support that at increased temperatures