Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• skeleton and a C5-keto group. Key strategies for the synthesis of depressin, as well as its casbene skeleton reported so far focused on the formation of the challenging 14-membered ring system. Cryptomeridiol (2) and 4-epi-cryptomeridiol (3) are two eudesmane-type sesquiterpene diols produced by a variety

• of different plants with broad biological activity. Most of the syntheses focused on the transformation of chiral pool substrates into their trans-6/6-fused ring system. We herein report the synthesis of compounds 1–3 by taking advantage of an expanded chiral pool strategy, in which the terpenoid

• hydroxy group allowed the synthesis of compound 1 from 4 in nine steps. Selective acid-mediated 5,10-transannular cyclization of 5 followed by hydration reaction furnished both products 2 and 3 in two steps. Keywords: chemoenzymatic synthesis; chiral pool; isopentenol utilization pathway; terpene

Harnessing light energy with molecules

• Grace G. D. Han,
• Mogens Brøndsted Nielsen and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2026, 22, 680–682, doi:10.3762/bjoc.22.52

• article by Wahl and co-workers [21], ring-opening of photogenerated azetidinols was used as a strategy for the convenient synthesis of aminodioxolanes. Photochemical denitrogenation reactions of bicyclic azoalkanes present a way to prepare strained bicyclic compounds. Further, Gomes and Lopez [22] report

Using generative AI to transform peptide hits into small molecule leads

• Joshua Mills and
• Yu Heng Lau

Beilstein J. Org. Chem. 2026, 22, 672–679, doi:10.3762/bjoc.22.51

• triaging generated candidates prior to more resource-intensive modelling, laboratory synthesis, and evaluation in functional assays. Deep learning for protein structure prediction The growing wealth of structural data in the Protein Data Bank, along with ongoing improvements in computational processing

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• amenable to scale-up, with continuous-flow operation delivering a significant increase in space–time yield, highlighting its potential for sustainable synthesis of CF3-containing molecules. Keywords: green chemistry; photocatalysis; photochemistry; trifluoromethylation; Introduction Trifluoromethylated

• , atom-economical, and cost-effective photocatalytic protocol for the trifluoromethylation of arenes and heteroarenes in a green solvent (Scheme 1e). The cost of reagents is one of the key factors in large-scale synthesis. We have updated the price comparison table of trifluoromethylating agents

• indicate that among the solvents employed in the procedures shown in Scheme 1, ethyl acetate represents a more environmentally sustainable alternative. Herein, as a continuation of our studies on photochemical approaches to the synthesis of fluorine-containing compounds [23][24][25] and on the development

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

• potent and selective PROTAC targeting CK2 might be valuable in the evaluation of specific degradation of CK2 as a therapeutic approach. Herein, we report the design and synthesis of a series of CK2-targeting PROTACs. CAM4066 was selected as the warhead to enable CK2-specific target engagement. We

• construction. The synthesis of the ATP-site binder began with the alkylation of commercially available methyl 3-aminobenzoate (3) using bromoacetyl bromide. Although initial purification via silica gel chromatography led to substantial product loss, isolation by simple aqueous workup afforded the intermediate

• synthesis see Supporting Information File 1, section 1.3). In parallel, PEG-based linkers bearing terminal alkyne handles were synthesised for modular CuAAC-based PROTAC assembly. The αD binder 16 had been synthesised via a two-step reaction. First, the phenolic group of 15 was converted into the

Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity

• Artem S. Sazonov,
• Dmitry A. Vasilenko,
• Denis V. Porfiriev,
• Yuri K. Grishin,
• Rimma A. Gazzaeva,
• Alisa P. Chernyshova,
• Maxim A. Kryakvin,
• Anna A. Baranova,
• Vera A. Alferova and
• Elena B. Averina

Beilstein J. Org. Chem. 2026, 22, 592–602, doi:10.3762/bjoc.22.45

• Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russian Federation 10.3762/bjoc.22.45 Abstract This study presents a novel regioselective synthesis of 3-electron-withdrawing-group-(EWG)-substituted 5-sulfonyl- and 5-sulfinylisoxazoles from 3-EWG-5-nitroisoxazoles via

• studies indicate that these compounds induce the bacterial SOS response without inhibiting DNA synthesis-related enzymes such as DNA polymerase I, DNA gyrase, or topoisomerases I and IV, suggesting activation via bacterial reductases. These findings highlight the potential of these isoxazole derivatives

• as promising antimicrobial agents and provide new insights into their mechanism of action. Keywords: antimicrobial activity; aromatic nucleophilic substitution; isoxazoles; oxidation; sulfonylisoxazoles; Introduction The isoxazole ring represents an important building block for the synthesis of

Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• . Synthesis of PROTACs towards FGFR2. Reagents and conditions: (a) K2CO3, Pd (dppf)Cl2, 1,4-dioxane/H2O 4:1, 100 °C, 5 h; (b) 3,5-dimethoxyaniline, Pd2(dba)3, BINAP, Cs2CO3, toluene, 100 °C, 12 h; (c) (2-bromoethoxy)-tert-butyldimethylsilane, NaH, DMF, rt, 12 h; (d) tetrabutylammonium fluoride, THF rt, 12 h

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt–Fe catalysts

• Hiroyuki Miyamura,
• Ryosuke Kajiyama,
• Shun-ya Onozawa,
• Yoshihiro Kon and
• Shū Kobayashi

Beilstein J. Org. Chem. 2026, 22, 575–582, doi:10.3762/bjoc.22.43

• , including ketones and aldehydes, to alcohols is a fundamental and important reaction in organic synthesis. One of the most ideal methods is catalytic hydrogenation, however, the hydrogenation of ketones generally requires harsh reaction conditions, such as high temperature and high pressure. We developed a

• : bimetallic nanostructure; carbonyl reduction; continuous-flow reaction; heterogeneous catalyst; subatmospheric hydrogen; Introduction The reduction of carbonyl compounds, ketones and aldehydes to alcohols is a fundamental and important reaction in organic synthesis that can provide valuable chemicals such

• ]. Recently, continuous-flow organic synthesis has attracted much attention from both academia and industry, because it offers numerous advantages, such as not only a high productivity with limited space but also realizing green sustainable syntheses minimizing required energy and resources. When

Kinetic resolution of racemic planar-chiral vinylcymantrenes by molybdenum-catalyzed asymmetric metathesis dimerization

• Haruna Imazu,
• Hitoshi Izu,
• Yasuhiro Ohki and
• Masamichi Ogasawara

Beilstein J. Org. Chem. 2026, 22, 568–574, doi:10.3762/bjoc.22.42

• resolution; molybdenum; olefin metathesis; planar chirality; Introduction The development of the well-defined molybdenum- [1][2] or ruthenium-alkylidene [3][4][5] catalysts has proven the olefin metathesis reaction to be a powerful tool in organic synthesis. Asymmetric extension is a recent trend in

• the excellent tolerance of the Mo-/Ru-metathesis catalysts toward the organometallic substrates. The olefin metathesis protocols could be extended to the asymmetric synthesis of diverse planar-chiral transition metal complexes either by the kinetic resolution of the racemic substrates [14][15][16] or

• demonstrated to be excellent chiral scaffolds in asymmetric synthesis, however, enantioselective synthesis of such planar-chiral complexes is still relatively undeveloped and remains as a challenging problem in asymmetric synthesis [24][25][26][27][28][29]. A new type of asymmetric olefin metathesis reaction

Molecular tweezer–peptide conjugates disrupt the protein–protein interaction between survivin and histone H3 essential in mitosis

• Catherine Gsell,
• Philipp Rebmann,
• Karina Opara,
• Christine Beuck,
• Peter Bayer,
• David Bier,
• Ingrid R. Vetter and
• Thomas Schrader

Beilstein J. Org. Chem. 2026, 22, 557–567, doi:10.3762/bjoc.22.41

• approximately 8-fold gain in affinity by attaching the tweezer moiety to the peptide, provided that the tweezer could reach a suitable binding partner as well. To allow a general commercial synthesis of the phosphorylated H3-peptide sequences for the tweezers, we used an azidoornithine extension at the C

Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• process, highlighting its precision and efficiency. Keywords: azides; 8-azidocyclooct-4-en-1-yl 4-nitrobenzoate; DFT; epoxycyclooctane azide; methanolysis; Introduction Organic azides are very important precursors for the preparation and synthesis of various nitrogen-containing compounds, as well as

• methodologies for the preparation of this class of compounds are of considerable interest. Azides have traditionally been used as protected primary amine equivalents. Therefore, in our previous studies, we employed azides containing eight-membered rings as precursors in the synthesis of C8-aminocyclitols [12

• ][13][14][15][16][17][18][19]. The ring-opening reactions of bicyclic epoxides are of significant importance and scientific interest due to their high ring strain, their strategic role in the construction of complex molecular architectures, and their utility in the synthesis of natural products

Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• synthesis of 4 and its possible isomer 3, the required compounds 1 and 2 were synthesized as a mixture of the isomers starting from chromene 5, briefly heated in a closed microwave apparatus with catalytic amounts of acetic acid. Forced heating of 5 in acetic acid or use of stronger acids lead to the

• diacetate (EDDA). However, synthesis of 2 was difficult. Despite numerous attempts, we only were able to get mixtures of both melifoliones with minor amounts of 2. Since all attempts to separate both isomers on a preparative scale failed, we were only able to record NMR spectra from a very small quantity of

• -position in regard to the OH-group at C-10b (Table 2). Synthesis of melifoliones Melifolione A (1) was prepared according to the method of Wang and Lee [5] by heating phloroacetophenone and citral with ethylene-diammonium diacetate (EDDA) in DMF. However, reaction of the educts in pyridine at 60 °C led to

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

• comparison of the synthesis and photophysical properties of the fluoro-substituted norbornadiene 1f with the ones of the parent compound 1b revealed that the yield of the Suzuki–Miyaura coupling reaction is significantly lower for the former [22], presumably because of the steric hindrance induced by the

• 19F NMR spectroscopy, further structural optimization is necessary for application purposes. Experimental Synthesis 1,3,5-Tris(bicyclo[2.2.1]hepta-2,5-dien-2-yl)-2,4,6-trifluorobenzene (1f) A mixture of 1,3,5-tribromo-2,4,6-trifluorobenzene (212 mg, 575 µmol), 4,4,5,5-tetramethyl-2-(bicyclo[2.2.1

• cycloreversion of 2a. Synthesis and photochromic reaction of trisnorbornadiene 1f to the trisquadricyclane 2f0,3 (numbering of quadricyclanes 2fm,n: m = number of norbornadiene units, n = number of quadricyclane units). Stepwise photoreaction of 1f to 2f0,3 (numbering of quadricyclanes 2fm,n: m = number of

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• approaches is rigorously ongoing. Recent procedures mainly focus on more efficient and scalable techniques for the assembly of the 4 key fragments of eribulin. But also new pathways for the total synthesis have emerged in the last decade. In this review the latest advancements towards the construction of

• eribulin are summarized. Keywords: breast cancer; drug manufacturing; eribulin; Halaven; total synthesis; Introduction Eribulin (1) is a truncated derivative of halichondrin B (2), a complex natural product originally isolated from the marine sponge Halichondria okadai (Figure 1) [1][2][3][4][5]. Already

• described the total synthesis of the marine natural product [19] and shortly thereafter, also its simplified structure, 1, was assembled and showed similar anticancer behavior [19][21]. Since 2010, the mesylate salt of 1 is approved by the U.S. Food and Drug Administration (FDA) for the treatment of

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

• capable of remediating uranium from aqueous environments [38][39]. Results and Discussion PCP HA synthesis and characterization Various strategies have been developed for the synthesis of hydroxamic acid derivatives over the years [40]. Classical and most popular routes involve the direct reaction of

• aldehydes [45], alcohols [46], and amides [47] have also been reported. However, the literature states that there is no particular reagent or reaction condition that can serve as a general rule for the synthesis of hydroxamic acids [48]. In this study, the direct reaction of hydroxylamine with the PCP ester

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

• LE1 7RH, UK 10.3762/bjoc.22.35 Abstract Class I histone deacetylases (HDACs 1–3) serve as catalytic subunits within seven multiprotein co-repressor complexes, each of which has distinct functions in the cell. We report the synthesis of a HDAC inhibitor–nanogold probe, derived from the class I HDAC

• synthesize a nanogold-conjugated HDAC inhibitor and evaluate its applicability in single-particle cryo-EM to unambiguously determine the positioning and orientation of the HDAC active site within the CoREST complex. Results and Discussion Design and synthesis of a HDAC inhibitor–nanogold probe For the basis

• routes (Scheme 1) [14][15][18]. Intermediates 5–7 were prepared in a manner analogous to Smalley et al. [14]. The first step in the linker synthesis for Au–(CI-994) involved a monoprotection of nonanedioic acid with a benzyl group to give 5 which proceeded in moderate yield due to the formation of the

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

• distal axial chiralities are widely applied in chiral ligands, natural products, and anticancer agents, with their unique spatial configurations endowing them with distinctive functions and values. Although significant progress has been made in the asymmetric synthesis of distal biaxial chirality

• biaxial chirality, multistep sequential generation, and conversion from central to biaxial chirality, with the aim of providing new perspectives and methodologies for further development in this area. Keywords: axially chiral compounds; stereoselective synthesis; Introduction In recent years, axially

• "-ternaphthalene compounds [35]. This work significantly advanced the development of bi- and multiaxial chirality. The synthesis of multiaxial chiral molecules requires appropriate steric hindrance to elevate the rotational energy barrier of each chiral axis [36], and the spatial interactions between axes are

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

• isomer 2 in agreement with the reports of Martinez and Koslov. Since the only reaction reported to give the benzo[c]phenanthridine isomer 1 is the three-component reaction that instead produces the isomeric benzo[c]acridine 2, we believe that the synthesis of benzo[c]phenanthridine isomer 1 remains

• diffractometer. Nuclear magnetic resonance spectra were recorded on a JEOL ECX400 spectrometer. Glutaminase assays were measured on a Tecan Infinite M nano spectrophotometer. Reagents and solvents for chemical synthesis were used without additional purification. Chemical synthesis 3-Bromo-4

Concept-driven strategies in target-oriented synthesis

• David Yu-Kai Chen,
• Chao Li and
• Yefeng Tang

Beilstein J. Org. Chem. 2026, 22, 451–454, doi:10.3762/bjoc.22.32

• history of science. Indeed, organic compounds have an unparalleled track record in elucidating the mysteries behind a wide range of physical, chemical, and biological phenomena, and advances in chemical synthesis have been instrumental in these explorations. Specifically, target-oriented syntheses of

• advancements, and strategic innovations. However, while efficiency and practicality remain essential design considerations in targeted synthesis, it is worth pondering whether the pursuit of efficiency (along with its associated elements) truly captures the underlying scientific essence of target-oriented

• synthesis. It is widely acknowledged that the initial allure of target-oriented synthesis often arose from the intellectually and aesthetically captivating strategies involved, with the mastery of synthetic design best exemplified through the perplexing structural relationships between target molecules and

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• Pharmacy, Shenzhen Technology University, Shenzhen 518118, China 10.3762/bjoc.22.31 Abstract The synthesis of racemic trans-taxifolin (trans-(±)-taxifolin) and its derivatives and subsequent chiral separation is the most prevalent chemical method to obtain enantiomerically pure taxifolin and its

• yields (20–41%) and proceeds without the use of explosive peroxides (such as H2O2), which are commonly employed in methods reported earlier. The avoidance of explosive peroxides in the present method enables safe operation, easy scale-up, and also the synthesis of taxifolin derivatives with oxidant

• -sensitive groups, largely expanding the substituent scope compared with the previous method. Keywords: Darzens reaction; derivatives; scale-up; synthesis; taxifolin; Introduction Taxifolin is a sub-member of the flavonoid family with outstanding bioactive performance [1]. Several in vitro and in vivo

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• oxacyclophene enabled the efficient and divergent synthesis of C6-substituted derivatives. The stereochemical analysis of the oxacyclophenes revealed that the iodo- and methyl-substituted derivatives have reasonable stereochemical stability. The planar chirality of the methyl-substituted oxacyclophene was

• -substituted oxacyclophenes 1ab (X = O, Y = Me), 1ac (X = O, Y = Ph), and 1ad (X = O, Y = I), in which 1ad was used as the key intermediate for the synthesis of 1ab and 1ac via Kumada–Tamao coupling with Grignard reagents (Figure 2). Results and Discussion Retrosynthesis and synthesis of the C6-iodo

• of propargyl alcohol 3 and the alkyne moiety in 3 can be introduced by an alkynylation of the formyl group of aldehyde 4. Thus, we started this synthesis from O-protected 2-bromobenzyl alcohol derivative 5 for the introduction of the propanal moiety of 4 by a Heck reaction with allyl alcohol. 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

• naphthalimide has also been explored to a considerable extent [45][46]. In general, the tert-butyl group has attracted considerable attention in drug design and synthesis due to its lipophilic character [47][48]. From the above-mentioned point of view, we have changed both sides of the substitution with a new

• 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

• compounds, making it a viable alternative for introducing long alkyl chains into selenium-containing systems towards lysosomal membrane permeability (vide supra) [42][43][44]. After synthesis, compounds 7 and 8 were thoroughly characterised using multinuclear NMR spectroscopy ¹H, ¹³C, and ⁷⁷Se NMR

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

• Compounds, Sh. Entuziastov 38, 105118 Moscow, Russia Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Leninskii pr. 31, 119991 Moscow, Russia 10.3762/bjoc.22.28 Abstract Efficient approaches have been developed for the synthesis of heteromultifunctional cone calix[4

• thermodynamic and kinetic stability of the capsules and the guest exchange processes [55][56][57][58][59][60]. This has made dimerization of tetraureacalix[4]arenes one of the most explored self-organization processes in calixarene supramolecular chemistry, which has been used in the template synthesis of

• herein report on the synthesis approaches to a series of cone p-aminocalix[4]arenes having propargyl or 2-azidoethyl groups at the narrow rims (Figure 1). The newly synthesized compounds may be thus treated as novel building blocks in calixarene chemistry capable of step-wise orthogonal transformations

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

• lines such as HepG2 (liver), HeLa (cervix), A549 (lung), and glioblastoma models rely on enhanced nucleotide metabolism to sustain rapid DNA/RNA synthesis. Oxazolopyrimidines can inhibit these overactive enzymes in cancer cells, while normal cells (with lower demand) are less affected. This explains why

• potential. Therefore, further functionalization of 2,4-diaryl[1,3]oxazolo[4,5-d]pyrimidines at position 7 of the structure-forming core was carried out in this work. Results and Discussion Chemistry The synthesis of 1,3-oxazolo[4,5-d]pyrimidine derivatives 1–9 was accomplished according to the previously

• ][1,5]diazocin-8-one) are commercially available reagents from Sigma-Aldrich. Aminoethylamines were synthesized according to the literature method [16] and used as racemic mixtures. General procedure for the synthesis of oxazolo[4,5-d]pyrimidines 1–9 A solution of 0.01 mol of the corresponding 7

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

• effects [14], сoagulation enzyme factor (FXa) inhibition [15] and antidepressant properties [16]. Considering the approaches to the synthesis of γ-aminosulfones, we focused our attention on the implementation of an aminoalkylation as a powerful and versatile tool for the synthesis of aliphatic amines [17

• commonly achieved by a classic nucleophilic substitution of a leaving group at the β-position relative to the N-protected nitrogen (Figure 2a). While this approach addresses most needs of targeted synthesis, developing alternative methods from inexpensive starting materials via domino-processes, allowing