Synthetic study of vic-bromination of diarylacetylenes, easy purification and separation

• Akane Togo,
• Hiyono Suzuki,
• Yuto Akai,
• Makoto Matsumoto,
• Yoshinori Suzuma,
• Hidehiko Kodama and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2026, 22, 795–802, doi:10.3762/bjoc.22.61

• , the E isomer could be recovered as a solid material by utilizing the difference in solubility. On the other hand, the Z isomer could be removed by filtration while remaining in solution. Keywords: bromination; diarylacetylenes; green chemistry; purification and separation; stereoselective reaction

• synthesis. In addition, we have found an easy purification and separation method of E and Z isomers of the crude product by using heptane. The method utilizes the difference in solubility of E and Z isomers. Because of this technique, the purification, separation, and scale-up were easy to perform. In this

• considerations, we found that E-2a could be isolated by only filtration, utilizing the difference in solubility of E-2a and Z-2a in heptane from the crude product. In Table 1, entry 1, the combination of NBS (2.2 equiv) and FeBr3 (1.0 equiv) for 2 h gave the ratio of E-2a/Z-2a/1a such as 86:14:0 by HPLC, in

Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators

• Xi Zhang,
• Jingyan Wang,
• Ziqiang Zhao,
• Caiyi Wang,
• Zenghui Ye,
• Wei-Yuan Ma,
• Jian-Xing Xu and
• Fengzhi Zhang

Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59

• replaced through conformational restriction to reduce potential toxicity. The hydrophobic spacer element offers some flexibility in shape and size, but the linker length must remain conserved. Furthermore, to address the issue of poor aqueous solubility, heteroatoms can be introduced into the aromatic ring

• , including the highly active component Z8. Despite a significant decrease in solubility due to its relatively high molecular weight, the compound's overall performance remains excellent. It was demonstrated that, in the absence of receptor overexpression, Z8 effectively activated FXR and inhibited ASK1

Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• donors [47] or, given the high solubility of Rongalite in water, phase-transfer catalysis [48]. Our earlier results indicate that tolerance of steric effects is greater in reactions with doubly electrophilic substrates that render the second conjugate addition intramolecular, justifying our choice of

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• fragments of natural molecules such as steroids, peptides or sugars, its solubility in water improves, thereby increasing the possibility of potential biological activity. In 2020, Martín and colleagues investigated fullerene 50 as a dipolarophile in 1,3-dipolar cycloaddition with azomethine ylide based on

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

• characteristics such as molecular weight, solubility, lipophilicity, lack of metabolic hot spots; and (3) well characterized structural information of their binding modes [118][119]. CRBN, one of the most commonly used E3 ligand to target E3 enzymes in PROTAC molecular design, has been successfully used to target

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• solubility in MeCN/H2O systems used for preparative purification; the compounds dissolved only in DMSO, explaining the diminished recovery. Nevertheless, the synthetic route successfully delivered two structurally distinct CRBN-recruiting CK2 PROTACs. All synthesised PROTACs 23–26, 28, and 29 were evaluated

• binding event (see Supporting Information File 1, section 2.1). This may have resulted from several factors, including the limited solubility of 24 under the conditions required for the assay and the requirement for cooperative ternary complex formation with the E3 ligase, as the isolated warhead–linker

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• corresponding hydroxamic acid, with no detectable acid-derived by-products. Solubility tests revealed that PCP HA is soluble exclusively in highly polar aprotic solvents (DMSO, DMF) and remains completely insoluble in other common organic solvents (chloroform, ether, etc.) and water. The absence of ligand

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• ]. Based on the Beer–Lambert law, the concentration was calculated to be 2.69 μM. Attempts at further concentration led to precipitation, indicating limited solubility at higher concentrations. The HDAC inhibitor–nanogold probe inhibits HDAC enzymatic activity in the CoREST complex We first wanted to

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• enhancing lysosomal membrane permeability and aqueous solubility [42]. Interestingly, for the first time, N-(n-octyl) chain substitution has been shown to demonstrate remarkable anticancer activity, particularly through tyrosine kinase inhibition, without significant DNA intercalation [43]. Among these

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• closed vessel to prevent the product oxidation. At the work-up step sodium hydroxide was replaced with potassium hydroxide which provided better water solubility of inorganic salts for their extractive removal. As a result, tetraamine 18 having four TBS-protected propargyl groups at the narrow rim was

• exclusive formation of heterocapsular assemblies, which was thus not hindered by the two triazole heterocycles arranged at the narrow rim of the calixarene core. Except for a slight broadening of the signals caused by the limited solubility of the compound, the 1H NMR spectrum obtained for a CDCl3 solution

• aqueous phase (at ≈4.8 ppm) along with a signal from dissolved water (1.56 ppm). Considering the low solubility of water in chloroform, the stability of the capsules in water-saturated CDCl3 seems reasonable, because the dimers are held together by at least 16 hydrogen bonds between the urea groups. On

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• pairs) can increase water solubility and facilitate salt formation. Introducing amino groups into heterocycles can have a significant impact on the anticancer activity of a compound [4][5]. Many studies have investigated the anticancer potential of heterocycle derivatives containing cytisine, glucamine

• combination of the [1,3]oxazolo[4,5-d]pyrimidin-7-amine fragment (structures A and B) with cytisine, glucamine, and aminoethylamine represents a promising strategy for the rational design of multifunctional hybrids with improved biological activity, water solubility, lower toxicity and target engagement

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• absorption (HIA), in vitro permeability to Caco-2 cells (Caco2), in vitro binding to plasma proteins (PPB), solubility, and inhibition of CYP2D6. The following were selected as descriptors of toxicity: carcinogenicity for rats and mice, mutagenicity according to the Ames test, and cardiotoxicity by

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• subsequent conversion into isopropyl and cyclohexyl esters. Cytotoxicity and antibacterial activity Selected synthesized compounds were evaluated for their antibacterial activity and cytotoxicity. The compounds exhibited poor water solubility but were readily soluble in DMSO. Experimental details are

Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF

• Ruiyan Wang and
• Yunan Wu

Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16

• -resolved biological imaging [6], chemical and biological sensing [7], as well as energy transfer and upconversion processes [8]. The unique characteristics of organic materials, including their solubility, ease of processing, molecular structure programmability, and the tunability of their emission color

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• -withdrawing leaving groups [49][50][54], and the transesterification of alkyl phosphates has rarely been observed [55]. A possible reaction pathway is shown in Figure 5. First, triethylamine increases the solubility of phytic acid in DMF by improving its lipophilicity and accelerates the formation of

• gives a lower yield because the phytic acid forms a syrup-like precipitate in the reaction mixture due to its poor solubility in organic solvents, thereby preventing efficient release of phosphoric acid into the reaction mixture. The plot depicted in Figure 4 shows that there is almost no induction

• -exchange resin to obtain phytic acid. Cation exchange was performed via a shaking method rather than a column method owing to the low solubility of phytate in water. The 31P NMR spectrum of the obtained phytic acid clearly shows four peaks corresponding to the non-equivalent phosphorus atoms in the phytic

Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• characterization of 25CN-NBOH and report key physicochemical properties in the solid state as well as in the solution state, namely stability, ionization, solubility, partition coefficient, and membrane permeability. We show that the hydrochloride salt is a stable and well-defined crystalline compound that is also

• respect to the physiochemical properties and handling of the compound in various research scenarios. Keywords: intramolecular hydrogen bond; membrane permeability; solubility; stability; synthesis; Introduction In recent years, classical psychedelics such as psilocybin and LSD have re-emerged as

• thermogravimetric analysis (TGA) curves did not show any significant mass loss prior to the melting point, further strengthening the conclusion that 1·HCl is not present as a hydrate or solvate upon crystallization from EtOH. Characterization of 25CN-NBOH (1) in solution 1·HCl displayed a thermodynamic solubility

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• ][8][9]. Analogous to the sulfonation of indigo to synthesize the water-soluble dye indigo carmine, compound 1 was sulfonated to increase its water solubility. Thus, the desired 6,6’-dibromo-5,5’-indigodisulfonic acid disodium salt (9) was obtained by heating 1 in a 2:1 mixture of oleum (20% free SO3

• indigo derivatives, an increasing number of sulfonic acid groups results in greater solubility of the 6,6’-dibromoindigo derivative (e.g., 10 has greater solubility in water than 9) [25]. When dissolved in aqueous solution, both 9 and 10 yield a bright blue solution. As shown in Figure 1A, salt 10

Design and synthesis of an axially chiral platinum(II) complex and its CPL properties in PMMA matrix

• Daiki Tauchi,
• Sota Ogura,
• Misa Sakura,
• Kazunori Tsubaki and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2026, 22, 143–150, doi:10.3762/bjoc.22.7

• spectroscopy, as well as high-resolution mass spectrometry (HRMS). Due to its low solubility, single crystals suitable for X-ray crystallographic analysis could not be obtained. Spectroscopic analysis and DFT calculations To elucidate the electronic structure of the platinum(II) complex, UV–vis absorption

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• ZnCl2·etherate exhibits superior catalytic activity compared to anhydrous ZnCl2. Although counterintuitive from the standpoint of Lewis acidity, this enhanced reactivity was attributed to the significantly improved solubility of the etherate complex, which compensates for its diminished intrinsic Lewis

One-pot synthesis of ethylmaltol from maltol

• Immanuel Plangger,
• Marcel Jenny,
• Gregor Plangger and
• Thomas Magauer

Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212

• amounts of sodium hydride and n-butyllithium followed by trapping with methyl iodide afforded mostly recovered maltol (2, 75%) along with traces of desired ethylmaltol (1, Table 1, entry 1). We attributed the low conversion rate to the poor solubility of the in situ-generated sodium maltolate and instead

• less nucleophilic and sterically more hindered base lithium diisopropylamide (LDA), the yield of ethylmaltol (1) increased to 25% and maltol (2) was recovered in 17% (Table 1, entry 3). Notably, treatment of maltol (2) with LDA resulted in a deep purple solution with no apparent solubility issues. We

• explore a modified and more selective approach with milder reaction parameters. In our revised strategy, we planned to introduce a transient protecting group for the free hydroxy group, thereby avoiding the necessity of dianion formation with the aim of improving solubility and stability (Table 2). We

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• . Additionally, some substrates proved incompatible with this reaction protocol. 2-Carboxybenzaldehyde did not result in the recovery of any solid product by simple filtration, probably due to its high solubility in water. Use of aliphatic aldehydes presented a significant challenge, as only the product 3z from

• File 1, Figure S251) in various solvents, including polar aprotic solvents (EtOAc, CH2Cl2, CHCl3, DMSO, and MeCN) and polar protic solvents (MeOH and H2O). However, the use of a non-polar solvent like hexane was not feasible due to the compounds' low solubility in this solvent. The 5-arylidene derived

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• caused by rotaxane 2, which lacks azobenzene switches, and axle 3, which lacks the macrocycle. Attempts to study the macrocycle alone without the axle were hindered by its very low solubility in the aqueous buffer. This study highlights both the potential and the limitations of rotaxane 1 as a membrane

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• , entry 1). However, methanol proved to be an ineffective solvent due to the rapid decomposition of NaBH4 and poor solubility of substrate 3. Most of the starting material was recovered unchanged after complete decomposing NaBH4. In contrast, when ethanol (Table 2, entry 2) or isopropanol (Table 2, entry

• solubility of the starting materials in methanol, which prevented efficient conversion. Subsequently, the substrates were introduced as THF solutions into NaOMe in methanol. Under these conditions, the cyclization did occur to form the corresponding Na salts of 3-hydroxy-TTs. Upon aqueous work-up and

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• but not limited to methyl laurate, has found application in a variety of direct and indirect food additive applications [94]. The Hansen solubility parameter is a numerical expression that quantifies a molecule's cohesive energy density from non-polar, polar, and hydrogen-bonding interactions. It is a

• space is shown in Figure 8a. The distribution of these selected solvents with other organic solvents in the 3D Hansen solubility space is determined by three Hansen solubility parameters (HSPs): dispersion (δD), polarity (δP), and hydrogen bonding (δH). As is well established, information about their

• similarity in solubility properties can be obtained from the distance between solvents. The identification of problematic and non-problematic solvents is facilitated by the size and color of the specific sphere representing a particular solvent. As demonstrated by the figure, the position of methyl laurate

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• (Figure S3) in Supporting Information File 1. WDG exhibited poor solubility, which hindered the direct acquisition of its single crystal structure for characterization. However, after Boc (tert-butyloxycarbonyl) protection, a single crystal structure (CCDC Number: 2339028) of the modified compound was

• by the two structural analogs, we added a commercially available tetrabutylammonium salt (TBAI) to the body dissolved in CDCl3 (TBAI has a good solubility in CDCl3) and studied the interaction between the receptor and iodide ion by 1H NMR titration, UV–vis absorption spectroscopy and fluorescence