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

• revealed the bi-lobed architecture of the CoREST complex and partial localization of the gold nanoparticle probe to the CoREST complex. However, the probe was not observed in classes showing the side-view of the CoREST complex, limiting unambiguous identification and positioning of the HDAC catalytic

• domain within the CoREST complex. Keywords: CI-994; co-repressor complex; CoREST; cryo-EM; gold nanoparticle; HDAC; Introduction Histone deacetylase (HDAC) enzymes catalyze the hydrolysis of acetyl groups from N-acetylated lysine residues in histone proteins. HDACs are also capable of the deacetylation

• localization within a cell, as well as in cellular cryo-electron tomography [11][12]. More recently, gold nanoparticles have been used as labeling tools in vitrified cells to locate cellular compartments in cellular cryo-EM [13]. Given the considerable utility of nanogold particles in microscopy, we aimed to

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• EtOAc (70 mL), which was separated and washed with water (3 × 50 mL). The organic layer was dried with anhydrous MgSO4, filtered, and the solvent removed by rotary evaporation to yield 3-bromo-4-dimethylaminobenzaldehyde as a thick gold oil (5.49 g, 89%). 1H NMR (400 MHz, CDCl3) δ 9.78 (s, 1H), 8.01 (m

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• cyclization to isothiazolones (Scheme 1). Silver- [20] and gold-catalyzed [21] hydrothiocyanations of haloalkynes with thiocyanate salts in acetic acid to give Z-vinyl thiocyanates were reported. The reaction between alkynic hydrazones and KSCN in AcOH/MeCN delivered N-iminoisothiazolium ylides [22] (Scheme 1

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

• compounds [79]. The colorimetric properties of rhodanine-derived compound 3n were used in the determination of silver [80] and gold [81] metals, and as a fluorescent sensor for detection of human serum albumin (HSA) [82]. Despite this, the TZD-derived compound 4n had its photophysical properties neglected

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• remains a major challenge due to the strong hydration of anions. Here, we report the preparation of silica gel functionalized with covalently anchored bambusuril macrocycles. In aqueous solution, this material efficiently sorbs dicyanoaurate(I), the key anion in gold mining, even in the presence of

• ; gold mining; macrocycles; Introduction Inorganic anions play essential roles in a variety of biological and biochemical mechanisms and are also involved in many industrial and manufacturing processes. Due to their significant environmental impact, it is important to monitor their presence and control

• is able to remove dicyanoaurate(I) anion from water, the principal cyanide-based species generated during gold mining processes. However, the use of the SG-BnBU material is problematic as BnBU can leach from the material into the solution. To address this limitation, we have developed and herein

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• ) compared to others, however, the difference is minimal. Still, the selectivity for Db1 and Db3 is comparable to or better than E, which currently is the gold standard for U-recognition. Db2 surprisingly demonstrated slightly higher affinity for the C–G base pair than for the desired U–A base pair. For both

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• , thereby avoiding the terminal cationic sites [25]. The shuttling is restored by the thermal reaction that regenerates the neutral acridane [24][25][26]. The same group also demonstrated that similar rotaxanes can be incorporated onto gold nanoparticles and retain their photoreactivity and switching

• innovations across multiple disciplines. Schematic of common rotaxanes (left) and depiction of the macrocycle shuttling (right). Structure of some common photoswitches integrated into rotaxanes. Rotaxane with an acridane photoswitch on the axle modulates the translation of a CBQT4+ macrocycle on gold

• nanoparticles. Figure 3 was adapted with permission of The Royal Society of Chemistry, from [21] (“Photoswitchable rotaxanes on gold nanoparticles” by Y. Duo et al., Org. Biomol. Chem., vol. 9, issue 9, © 2011); permission conveyed through Copyright Clearance Center, Inc. This content is not subject to CC BY

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• 1,5-enynes 1 as substrates involving alkyne alkoxylation and dienol ether aromaticity-driven processes (Scheme 2) [8]. The reaction pathway was decisively influenced by the choice of solvent. Under gold catalysis, with toluene as the solvent and 2 equiv of methanol serving as the nucleophile, the

• reaction proceeded via 5-endo-dig cyclization. This pathway involved enol ether attack on the gold-activated alkyne, leading to the formation of oxonium intermediate 2. Subsequently, nucleophilic addition of methanol culminated in the formation of indene motif 5 (Scheme 2, path a). When methanol served

• dual roles as solvent and nucleophile, the gold-catalyzed intermolecular Markovnikov addition of methanol to the gold-activated alkyne proceeded to afford dienol intermediate 4. The intermediate 4 subsequently underwent a regioselective 6-endo-trig cyclization, generating the naphthalene core 7 (Scheme

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• -linking of polymers (such as PLGA and PEG), inorganic materials (such as gold and silica), or biomolecules (lipids and proteins), enabling efficient drug loading and controlled release [66][67][68]. Among them, amphiphilic CAs that incorporate both hydrophilic groups and hydrophobic alkyl chains through

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• Cope rearrangements [20]. More recently, Alabugin and co-workers reported that the gold(I)-catalyzed propargyl rearrangement depicted in Scheme 1b also follows a concerted oxonia Claisen pathway (via an aromatic TS) rather than through a higher barrier 6-endo-dig cyclization [21], which provides

• process occurs in a concerted manner through the corresponding five-membered transition state, the germanium and magnesium cyaphide complexes are significantly more reactive (i.e., leading to a lower-barrier process, ΔG≠ ≈ 20 kcal/mol) than their platinum or gold counterparts, which exhibit barriers

• process up to the corresponding transition states. It is found that the lower barrier computed for the cycloaddition involving the Mg cyaphide complex does not originate from the strain energy, which is actually much less destabilizing for the analogous reaction involving the gold(I)–cyaphide complex

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• excellent UV stability and solvent-dependent fluorescence [91]. Protonation significantly enhanced their emission intensity, and the presence of nitrogen facilitated further structural derivatization. In the same year, Alcarazo’s group reported an enantioselective gold-catalyzed synthesis of compound 78

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• ]. These oxetanone precursors are generated from easily accessible alkynylphosphonates 124 via gold-mediated alkyne oxidation by pyridine N-oxide 125 followed by a formal O–H-insertion of the resulting metallacarbene intermediate 128. The optimised procedure requires 5 mol % loadings of the gold catalyst

• synthetic route to the repertoire which proceeds through a gold-catalysed oxidation of propargyl alcohol (131) [82]. Scheme 34 also shows selected transformations from the publications by Carreira et al. to provide a brief insight into what oxetane building blocks can be prepared from 3-oxetanone: these

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• dimerization of alkynes, followed by the expansion of a phenyl ring leading to the formation of an azulene moiety, was first reported over half a century ago. These reactions can be carried out using various catalytic systems, including sulfenyl chloride/AlCl3 [50], palladium catalysts [51] or gold catalysts

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• . Practical applications of this ability are directed to the selective isolation of gold from a variety of sources, spanning from gold-rich mining ores and tailings/mining wastes to gold-bearing metal scraps obtained from disposed electronic devices. Moreover, it describes the development of a method based on

• spontaneous complex formation between α-CD and tetrabromoaurate and its current status of use in a few mining sites in the United States. Keywords: bromoaurate; cyanoaurate; cyclodextrin inclusion; self-assembly; supramolecular interactions; Introduction Gold has allured and captivated humankind ever since

• its discovery, mostly because of its glittery metallic yellow color and its ability to remain untarnished even after exposure to extremely aggressive conditions. Gold is able to keep its shine for centuries, having been deemed as the most noble of metals [1]. Present in human life since early

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• . Furthermore, Sato and co-workers (2019) employed an air-stable Ni nanoparticle supported on sulfur-modified gold (SANi) to convert alkynes to the corresponding cinnamic acids 285–287 (Scheme 70B) [120]. In addition, the SANi catalyst could be recycled without significant loss of activity. By generating CO in

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

• the α-position of enamide to be an active cyclization site, with the alkyne tether acting as the nucleophile. Since it is well-established that alkynes, when activated by transition metals such as gold or platinum, can also function as electrophiles, modulating the reactivity of the decahydroquinoline

• was utilized to transform enamine 18 and propargyl ester 19 into 1-azaspiro[4.4]nonane 20 with high diastereoselectivity. Notably, the combination of an N-heterocyclic carbene gold catalyst and a silver salt AgSbF6 was found to be essential in guaranteeing the reactivity of the alkyne partner

• , probably due to the formation of a more acidic cationic gold complex. Following this annulation, reduction of the amide in 20, catalytic hydrogenation of the alkene and the N-benzyl group, and subsequent nitrogen acylation yielded chloride 21 in a 42% total yield, setting the stage for the Witkop

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• character of the fluorine substituent. When gold atoms are coordinated to the pyridine nitrogen, a ϕ as high as 8% has been observed [57]. The reason for this increase in ϕ to 8% for Au-Cl2PyBTM and 20% for Au-F2PyBTM is unknown, but the increase in the presence of a heavy atom might point at an improved

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• ][44] and hydroalkoxylations [45]. In 2013, Van der Eycken and co-workers described an intramolecular cationic gold-catalyzed post-Ugi heteroannulation of imidazoles with activated alkynes for the diversity-oriented synthesis of imidazo[1,4]diazepines 13 from Ugi-derived propargylamides 12 (Scheme 1c

• ) [46]. In 2019, Li, Yang, Van der Eycken and co-workers reported a modification of this strategy relying on thermal activation instead of cationic gold catalysis [47]. The approach worked particularly well with substrates featuring terminal alkynes. Inspired by these developments and taking into

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• in steering catalytic selectivity. In 2016, the Jiang group achieved regioselective control in the gold-catalyzed intramolecular hydroarylation of alkynes by modulating the electronic and steric effects of ligands (Scheme 2) [20]. Mechanistically, the electron-deficient phosphite ligand L1 and the

• weakly coordinating OTf− anion synergistically enhanced the electrophilicity of the gold center, enabling coordination with the amide group to form a three-coordinate Au(I)–π-alkyne intermediate Int-12. The umbrella-shaped steric shielding provided by the ligand-stabilized intermediate Int-9, followed by

• tactics in chemical synthesis. Ligand-controlled regiodivergent C1 insertion into arynes [19]. Ligand effect in homogenous gold catalysis enabling regiodivergent π-bond-activated cyclization [20]. Ligand-controlled palladium(II)-catalyzed regiodivergent carbonylation of alkynes [21]. Catalyst-controlled

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• strategies for cyclobutyl scaffolds [53][54][55], products 6 and 7 could be synthesized via mild conditions [68]. Inspired by recent advances by Nolan and co-workers demonstrating the synthetic power of gold catalysts in EnT catalysis [31][69][70][71][72], we probed the reactivity of [Au(SIPr)(Cbz)] in our

• achieved. It is pertinent to note the enhanced levels of diastereoselectivity obtained for this reaction further underscore the potential of gold catalysts for future EnT reactions. Control reactions indicate selective activation of the α,β-unsaturated ester (see Supporting Information File 1 for full

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

• the most used one. This is usually done at a load of 5 mol % in CH3CN as solvent and CH2Cl2 as a C1 synthon, under moderate reaction conditions (60 °C). Consequently, this synthetic strategy is less dependent on temperature compared to AAA coupling [62]. Several reports also showed that gold (as AuCl3

• 27 and alkynes 28 (Scheme 21) [63]. In this case, the catalysis was accomplished by a gold(III) catalyst. In general, CH2Cl2 is preferentially chosen as the dihalomethane compound due to economic reasons and ease of access, but some reports also used CH2Br2 and CH2I2 with good results [62][66][67

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

• of side reactions. This latter advantage has been notably exploited in the case of ring-closing olefin metathesis reactions, where Weizmann et al. utilized the photothermal response of plasmons from gold nanoparticles to activate the catalyst [17]. This approach contrasts with the work of Rovis et al

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• coupling with gold(I)-mediated 6-endo cyclization streamlines the rapid and modular assembly of the substructure of bis-tetrahydroisoquinoline (THIQ) alkaloids. The design of the key synthetic intermediate bearing a 2,3-diaminobenzofuran moiety allows both gold(I)-mediated regiocontrolled 6-endo

• involvement of a fluorescent intermediate in the cascade synthetic process. Keywords: cascade reactions; copper-catalyzed three-component coupling; gold-mediated 6-endo hydroamination; tandem cyclizations; tetrahydroisoquinoline alkaloids; Introduction The bis-tetrahydroisoquinoline (THIQ) alkaloid family

• , followed by gold(I)-promoted 6-endo cyclization between the internal alkyne and 2,3-diaminobenzofuran moieties with spontaneous transformations into the left THIQ segment in 14. Results and Discussion As outlined in our modular synthetic approach (Scheme 1c), the copper(I)-catalyzed three-component

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

• instead proceeded with addition of dichloro(pyridine-2-carboxylato)gold(III) complex in combination with silver triflimide, AgNTf2. A range of β-fluoroazepanes 7 were successfully synthesised with high enantiomeric purity in good yields. A mechanism for the synthesis of β-fluorinated piperidines was

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

• ) Superposition of docked compounds 4a–e and 5e in a CYP51 ACb. aThe amino acid residues of the protein are colored green, compound 4e is colored gold and the haem is colored grey. The heterocyclic nitrogen of compound 5e appears to be orientated towards iron and is located 2.8 Å away from it, which may indicate