Get a better glimpse on sequential photoreactions of trisnorbornadienes with ¹⁹F NMR spectroscopy

• Julian Felix Maria Hebborn,
• Ben Eric Merten,
• Thomas Paululat and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 527–534, doi:10.3762/bjoc.22.38

• exemplarily with a trifluorinated trisnorbornadienylbenzene that 19F NMR spectroscopy may be applied as a useful complementary method for the investigation of sequential photoreactions. The trisnorbornadiene core structure was used as it figures as promising scaffold for molecular solar thermal (MOST) energy

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

• extractants. Here, we report the design and synthesis of PCP HA, a phenoxycalix[4]pyrrole scaffold functionalized with four hydroxamic acid (HA) groups, and evaluate its uranium(VI) extraction potential. PCP HA was synthesized from its ester precursor (PCP E) via hydroxyaminolysis using KOH, achieving a 95

• scaffold functionalized with four hydroxamic acid groups, and demonstrated its uranyl extraction potential. Solid–liquid extraction studies showed that it removes up to 95% of uranyl at pH 3. Subsequent investigation at pH 4 revealed that a 7:1 ligand-to-metal molar ratio is sufficient to achieve near

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• conjugated 1,3-diene scaffold though a Pd(II)-catalyzed strategy involving a thioether-directed alkenyl C–H olefination (Scheme 21) [60]. Pleasingly, the strategy also enabled the synthesis of stereoisomers having two stereogenic axes with high enantioselectivity. The axially chiral styrenes produced in this

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

• and stabilizes a catalytically inactive form of the enzyme [11][12]. The BPTES scaffold has undergone significant medicinal chemistry development resulting in CB-839/telaglenastat, which is being evaluated in clinical trials in combination with other anticancer agents [13]. Compound 968 is a third

• found to suppress the growth of a luminal breast cancer cell line that expresses GLS2 and is insensitive to GLS1-specific inhibitors such as BPTES and CB-839 [22]. After initiating a project to synthesize derivatives of compound 968, we searched the literature for synthetic routes towards its scaffold

• or benzo[c]acridine 2. Clarifying this issue would benefit the community of cancer biologists who use compound 968, enable medicinal chemistry around the compound 968 scaffold, as well as correct the structure displayed by vendors of this compound. Results and Discussion To determine whether the

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

• Discussion Chemistry Scheme 1 illustrates the synthesis of naphthalimide-organylselanyl conjugates 7 and 8. The incorporation of the organoselenide moiety into the naphthalimide scaffold was achieved via a nucleophilic substitution reaction. The bromine atom in the bromonaphthalimide precursor 12, prepared

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

• regulation of the cell life cycle [8]. On the contrary, oxazolo[4,5-d]pyrimidines represent a poorly studied class of compounds because of limited access to this scaffold [9]. An in silico study showed that both isomeric forms of oxazolopyrimidines can form stable complexes due to hydrogen bonds between a

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• antiandrogen cancer treatment [8][9] (Figure 1). Moreover, aminosulfones remain a privileged scaffold in the ongoing development of new methods for the synthesis of pharmaceuticals [10][11][12], with multiple research compounds showing promising bioactivities such as MMP inhibition [13], antiinflammatory

• quaternary ammonium salt of 3,3-dibenzoylpyrrolidine, derived from dibenzoylmethane, undergoes ring-opening in the presence of a nucleophile and sodium methoxide via a retro-Claisen reaction [33]. This process yields 4-(dimethylamino)-2-heteromethyl-1-phenylbutan-1-one scaffold V (EWG = COPh; Y = OR, SR, NR

• solution of dimethylamine did not affect the process and bis-dimethylamino product 4l was readily isolated in 97% yield. The obtained 2-(phenylsulfonyl)butane-1,4-diamines 4l–p represent the biogenic amine putrescine scaffold, incorporating dialkylamino or azaheterocyclic motifs such as pyrrolidine

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• enables selective oxidative hetero-coupling followed by dehydrative cyclization, furnishing the extended [8]helical scaffold efficiently under mild, oxidant-free conditions. Structural analyses show retained aromaticity, increased helical distortion, and higher configurational stability (≈38 kcal/mol

• hetero[8]helicene (Scheme 1C). This strategy delivers the target scaffold in only three steps from commercially available substrates and exploits the differential oxidation potentials of the two partners to enforce chemoselective cross-annulation. To the best of our knowledge, this represents the

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• nitroxides are incorporated into macromolecular or nanosized supramolecular structures, which modulate nitroxide properties. For example, the efficiency of ORCA (relaxivity) directly depends on the rotational correlation time of the radicals attached to the scaffold [13][14][15]. Large structures in which

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

• 21st century, this research culminated in the approval of the first drug whose active molecule contained a spirobarbiturate scaffold – zoliflodacin© (Scheme 1) [7]. Due to the significance of spirobarbiturates, numerous approaches have been devised for their synthesis [13][14][15][16][17][18][19

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

• Fe3O4@SiO2–SO3H nanoparticles [39]. However, all previously reported multicomponent protocols inevitably terminate at the formation of the cyclic pyranoquinolinone scaffold, and no controlled access to open-chain quinolinone esters has been demonstrated so far. Herein, building upon previous studies and

• demonstrate pronounced antibacterial activity, their low toxicity toward human cells and distinctive molecular scaffold render them promising candidates for further development as biologically active agents. Conclusion In conclusion, we have developed a novel organocatalyzed four-component cascade reaction

• potential of the 4-hydroxyquinolin-2(1H)-one scaffold as a versatile template for future targeted modifications to develop active derivatives. Examples of biologically active quinolin-2(1H)-ones. Structures obtained via rational design aimed at enhancing antibacterial activity. In vitro antibacterial

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• oxygen atoms from the substrate and the metal catalyst, which fixed the conformation of the polycyclic scaffold. As a result, the top face is sterically less favored, thereby hydrogen approaches from the opposite face. The subsequent addition of another two equivalents of hydrogen also supported this

• dihydronaphthyridine core, which presents a unique synthetic challenge. Given that (−)-finerenone is presently undergoing phase III clinical trials, the development of efficient and scalable methods for constructing the dihydronaphthyridine scaffold has become a focal point of interest in synthetic chemistry. In 2020

• (Scheme 31) [102]. In the presence of NBS as the oxidant, precursor 206 undergoes an aza-Achmatowicz rearrangement to give the monobrominated intermediate 207, which upon treatment with NaHCO3 furnishes the spirocyclic scaffold 208. From this versatile intermediate, a range of oxindole natural products

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• achieve C–C connections (dark green) in a semisynthesis (with most of the required carbon atoms being already part of the starting material). Highlight of this synthesis was the key biomimetic rearrangement in the middle of the sequence, furnishing the C-nor-D-homo scaffold. This synthesis provided the

• rearranged scaffold 85 in three steps. Acetyl protection and elimination at C9–C11, followed by a Birch reduction, yielded a dienone structure. The latter was then hydrogenated, a methyl group was installed in α-position to the ketone, and an enone was formed to give 81 over 12 steps. Then, 2-ethyl-5

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• of male sexual disfunction. A review published in 2020 [12] gives an excellent overview about the medicinal chemistry of compounds incorporating a 1,4-benzodioxane scaffold variously substituted either on the aliphatic or on the aromatic carbon atoms. In connection with our present work, the latter

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

• , hybrid compounds combining the imidazo[1,2-a]pyridine scaffold with the thiazolidine nucleus were synthesized. Initially, aldehyde derivatives of the GBB adducts 8 were prepared from 2-aminopyridines 5, terephthalaldehyde (6), and isocyanides 7 using a green methodology that employed phosphotungstic acid

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• embellished by additional bridging via a γ-lactone and a γ-lactol ring, resulting in a caged pentacyclic scaffold with a 5/5/5/5/5 ring arrangement. The compound demonstrates neuroprotective activity by mitigating oxygen-glucose deprivation-induced cell injury in SH-SY5Y cells. Since its isolation in 2017

• strained trans-pentalene subunit. This carbon ring system is further bridged with a γ-lactone and a γ-lactol ring, forming a caged pentacyclic scaffold with a 5/5/5/5/5 ring arrangement. Illisimonin A was thus classified as an illisimonane-type Illicium sesquiterpene, and its carbon skeleton was designated

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• the correct structure of ryanodol to be 3-epi-ryanodol (5), thereby revising the previously accepted configuration [15]. Since then, numerous analogs based on the ryanodol scaffold have been identified and characterized. As of now, 18 natural products from this family have been successfully isolated

• core tricyclic carbon skeleton, and (2) systematic oxidation state manipulation of this scaffold to precisely introduce its dense array of oxygenated stereocenters. The construction of the C6 quaternary stereocenter represented a particularly formidable challenge in the late stage. This was

• scaffold yet exhibit diverse oxidation patterns and stereochemical configurations, with ryanodine (1) representing a landmark example (Table 1). This review has highlighted synthetic investigations of Ryania diterpenoids by various research groups, encompassing brief discussions of their isolation

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• , and low toxicity make calixarene derivatives valuable drug candidates against cancer. The aim of the present study was the synthesis and characterization of a calix[4]arene derivative in which known anticancer isothiouronium groups were clustered on a calix[4]arene scaffold bearing long C12 alkyl

• leukemia cells and low toxicity toward non-cancerous cells [43]. Therefore, the aim of this study was to evaluate whether introducing isothiouronium moieties at the upper rim of a calix[4]arene scaffold, bearing long C12 alkyl chains at the lower rim, could yield a novel derivative (compound 3) with

• discriminate between normal and cancer cells, as demonstrated by the calculated SI of 0.47. The high SI value by compound 3 evidenced the isothiouronium moieties retain the selective cytotoxicity towards cancer cells also when tethered to the calixarene scaffold. Since the long alkyl chains in compound 3 could

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

• functionalized. We noted that isoorotic acid offered an opportune core from which to prepare extended nucleobase monomers through amide bond formation (Figure 3a) [34]. Secondly, the work began with the initial goal to find an extended nucleobase scaffold capable of strong binding to A and then reverse its point

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

• as agonists of the GPR35 receptor [22], further underscoring the value of the TT scaffold in enzyme- and receptor-targeted drug discovery. Given the established practical significance of thieno[3,2-b]thiophene compounds, the construction of molecules featuring the TT core remains a key objective in

• organic synthesis. A widely adopted strategy for building the TT scaffold involves the annulation of a second thiophene ring onto a suitably functionalized thiophene precursor. Most commonly, this approach starts from halogenated thiophenes such as 3-bromo- or 3-chlorothiophenes, which undergo subsequent

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• ; palladium; Introduction Carbazole represents an important heterocyclic scaffold that is broadly present in many natural products, biologically active motifs, as well as optoelectronic and functional materials [1][2][3][4][5][6][7][8]. By virtue of its substantial application in various fields, significant

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• 6,5,6-abeoabietane scaffold and impressive antitumor activity. α-Diazoketone 124 was synthesized from commercially available 1,2,4-trimethoxybenzene (123) [64] by a series of synthetic transformations, and converted by Wolff rearrangement to esters 125 and 126 with a trans-fused 6,5,6-ring system

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• bioactive molecules (Figure 1). This scaffold exhibits a broad range of pharmacological activities, including significant in vitro antimycobacterial properties [4], potent antitumor effects against melanoma cell lines [5], and antagonism of TH2 lymphocyte function [6]. Due to their wide-ranging biological

• under heating furnished chiral spiroindolylpyrroles in excellent yields and enantioselectivity (Scheme 1, path d) [11]. Moreover, a copper-catalyzed reaction of oxindole-derived alkenes with acetophenone O-acetyl oxime has also been employed to construct the spiroindolylpyrrole scaffold (Scheme 1, path

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• this key intermediate in hand, β-hydroxy acid 29 was synthesized through deprotection, IBX oxidation, and Pinnick–Lindgren–Kraus oxidation and the β-lactone 13 was subsequently obtained through activation of the carboxylic acid. Although we successfully constructed the molecular scaffold of

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• ). Dysifragilone A (34) displays stronger inhibition of NO production than hydrocortisone, with an IC50 of 6.6 μM. Dysideanone B (35) shows cytotoxicity against HeLa and HepG2 human cancer cell lines, with IC50 values of 7.1 and 9.4 μM, respectively. Septosone B (37), featuring an unusual spiro[4.5]decane scaffold