Synthesis of novel 1,2,4-oxadiazole-isoxazoline hybrids and their in silico potential with adenosine receptors

• Pshtiwan S. Mohammed,
• Mohammed K. S. Dalo,
• Onur C. Yazıcı,
• Muhammet Yildirim and
• Akın Sağırlı

Beilstein J. Org. Chem. 2026, 22, 1033–1047, doi:10.3762/bjoc.22.82

• validate their therapeutic potential. Keywords: aldoxime; antiparkinson; 1,3-dipolar cycloaddition; isoxazoline; 1,2,4-oxadiazoles; Introduction 1,2,4-Oxadiazoles are pharmacologically significant five-membered heterocyclic rings, primarily recognized for their bioisosteric relationship with ester and

• dipolarophiles [54][55][56][57]. Despite the proven efficacy of both heterocyclic rings as pharmacophores, reports focusing on the synthesis of 1,2,4-oxadiazole-isoxazoline hybrids remain scarce. Previous studies have suggested that such hybrid structures may exhibit phosphodiesterase IV inhibitory activity or

• cycloadditions of heterocyclic chlorooximes with methyl 2-propenoate [59]. Furthermore, sequential nitrile oxide cycloaddition reactions of benzonitrile and mesitonitrile oxides with cinnamonitrile were reported as an efficient route to structurally diverse 1,2,4-oxadiazole-isoxazole hybrids [60] (Scheme 1). On

Synthesis and optical resolution of 4,5-diaminohomoadamantane: a promising scaffold for chiral ligands and bioactive compounds

• Polina A. Man’kova,
• Vadim A. Shiryaev,
• Olga S. Podlipnova,
• Marat M. Khisyamov,
• Dmitry S. Nikerov,
• Alexander N. Reznikov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2026, 22, 1013–1022, doi:10.3762/bjoc.22.80

• high analgesic activity in a mouse model of cystitis (Figure 1) [63]. Vicinal diamines are of interest to chemists not only as precursors for the synthesis of heterocyclic compounds, but also because of their wide range of practical applications. Structures with a 1,2-diamine fragment are widely used

Rh(III)-catalyzed chelation-assisted C–H activation/annulation of 2-arylimidazolines with cyclic diazo-1,3-dicarbonyl compounds: a novel approach to tetracyclic annulated derivatives of 2,3-dihydroimidazo[2,1-a]isoquinoline

• Ivan Lyutin,
• Grigory Kantin,
• Olga Bakulina and
• Dmitry Dar'in

Beilstein J. Org. Chem. 2026, 22, 997–1003, doi:10.3762/bjoc.22.78

• ) [23]. Interestingly, the latter reacted with ring-opening of the initial heterocyclic moiety. In the present work, we have extended this strategy to annulation of 2-arylimidazolines, which opened the way to several types of new medicinally relevant azatetraheterocycles having a 2,3-dihydroimidazo[2,1

• , as we were unable to find any published successful examples of Rh(III)-catalyzed chelation-assisted C–H activation/annulation with diazo compounds when such heterocyclic substrates were used as CH-components. Substitution at position 4 of the imidazoline ring with a methyl group resulted in the

• substituent at the imidazoline ring) were successfully introduced into the target reaction. Two heterocyclic diazo diketones were introduced to this annulation approach for the first time. This strategy allowed preparation of 17 novel structurally diverse annulated derivatives of 2,3-dihydroimidazo[2,1-a

Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• suitable ligands such as N-heterocyclic carbenes or electron-rich phosphines, the deprotonation of an N–H heteroaromatic can generate a copper–amido intermediate [32][33][34]. These species typically exhibit enhanced nucleophilicity and can engage alkenes via the direct nucleophilic addition of a copper

• the direct hydroamination of alkenes using aromatic amines and aza-heterocyclic N–H nucleophiles under copper catalysis. The primary focus is on the mechanistic paradigms, Cu–amido pathways, Lewis acid activation, and carbon-radical manifolds, and on how these distinct activation modes translate into

• characterization of well-defined copper–amido complexes I and II, supported by electron-donating ligands such as phosphines and N-heterocyclic carbenes (NHCs) (Scheme 2) [32][33][34]. Copper–amido complex I was prepared by treating the dtbpe-ligated Cu–Cl complex (dtbpe = 1,2-bis(di-tert-butylphosphino)ethane

Palladium-catalyzed benzocyclization reactions of quinoline-2-carboxamides via sequential C–H/N–H functionalization

• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2026, 22, 905–914, doi:10.3762/bjoc.22.71

• corresponding heterocycle-fused compounds. The high chemoselectivity of the 1,2-dihaloarene functional groups is confirmed in this reaction, thus enabling divergent synthesis of various multifused heterocyclic systems. Keywords: C–H activation; chemodivergent synthesis; C–N coupling; fused-ring system

Cascade transformation of 2-(diazoacetyl)-2H-azirines to 2-aroyl-3-hydroxy-1H-pyrroles via condensation with aromatic aldehydes

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2026, 22, 897–904, doi:10.3762/bjoc.22.70

• [4.1.0]heptan-5-one derivative. The acid-catalyzed transformation of which leads to 2-aroyl-3-hydroxy-1H-pyrroles. Keywords: azirines; condensation; cyclization; diazo compounds; pyrroles; Introduction Diazo compounds play a significant role in the synthesis of heterocyclic compounds, which explains

• the ever-growing structural diversity of such molecules and the variety of their transformation pathways [1][2][3][4][5][6][7][8][9][10]. Azirinyl-substituted diazo compounds, which we have recently introduced into the heterocyclic synthesis arsenal [11][12][13][14][15][16][17][18][19], are

• ][18], and heterocyclic hybrids [11][19]. However, the diversity of known azirinyl-substituted diazo compounds is currently limited to diazo ketones [11][12][13][15], 2-(diazoacetyl)-2H-azirines, α-diazo-β-ketoesters [14][16][17][18][19], and alkyl 2-diazo-3-oxo-3-(2H-azirin-2-yl)propanoates

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

• approach to the synthesis of a rare heterocyclic system, a fully hydrogenated pyrrolo[2,1,5-cd]indolizine derivative [72] (Scheme 29). The process begins with the 1,3-dipolar cycloaddition of azomethine ylide, obtained from glycine methyl ester (62) and cinnamaldehyde (56), to N-phenylmaleimide (63) to

• reactions proceed with high stereoselectivity, providing products with eleven chiral carbon atoms in three steps. In 2018, Zhang and co-workers presented a sequential process based on a combination of inter- and intramolecular (3 + 2) cycloaddition reactions to prepare highly fused heterocyclic systems

• diastereoselectivity of the reaction, have a significant impact on enantioselectivity. The same bifunctional squaramide L24 showed better efficiency as a catalyst for the (3 + 2) cycloaddition reaction of azomethine ylides from isatin and benzylamines to nitroalkenes [100]. A wide variety of heterocyclic systems have

Hydrogen production from formic acid catalyzed by NHC–Cu complexes

• Orlando Santoro and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2026, 22, 620–627, doi:10.3762/bjoc.22.48

• equimolar mixture of H2 and CO2. The efficiency of the catalysis showed to be strongly dependent on the nature of the amine. Keywords: copper N-heterocyclic carbene; formic acid dehydrogenation; hydrogen storage; metal hydride; silanes; Introduction The discovery and utilization of alternative and

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

• -Naphthaldehyde (1s) and salicylaldehyde (1t) were hydrogenated quantitatively, and analytically pure products were isolated by simple evaporation of the collected fraction eluted from the flow reactor (Table 2, entries 19 and 20). Heterocyclic aldehydes 1u and 1v were also applicable, while the conversion of 1v

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

• contraction of the acetyl phenol to a furanone ring, forming the derivatives 11 and 12, whose structures were confirmed by X-ray analysis. A hypothetical mechanism for the oxidative ring contraction is proposed. 11 and 12 are the first representatives of new heterocyclic ring systems that have not previously

• been described in the literature. Keywords: Melicope barbigera; Melifoliones A and B; new heterocyclic ring systems; new natural compounds; para-quinols; phenol oxidation; Introduction The genus Melicope is a member of the Rutaceae (Citrus family) and contains more than 200 species distributed in the

• and 14 seems also to be possible [19] (Scheme 5). Compounds 11 and 12 are the first representatives of two new heterocyclic ring systems consisting of two pyran rings, one cyclohexane and one furan ring. Conclusion Finally, it remains to be noted that it was not possible to prepare the quinols 3 and 4

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

• C1–C13 fragment 11 with C14–C35 fragment 12 [66][67][68]. Despite these great advances, still, the research on improving synthetic efficiency, reducing production costs, omitting toxic chemicals, as well as on new pathways towards 1`s 4 heterocyclic precursor fragments is rigorously ongoing [69][70

• also considerable amounts of 183`s epimer were formed (2:1 dr). Oxidation with DDQ removed the Bn-moiety (184) and triggered ketalization towards 185. Eventual mesylation formed key fragment 186 in 95% yield. For the assembly of both heterocyclic subunits of 186, Nicholas etherification and radical

• field of the synthesis of 1. This is especially observable for the synthesis of the 4 heterocyclic key fragments or intermediates obtained during the Eisai process. Here, the major progresses can be registered in terms of enhancing the sustainability of pathways through the removal of metal catalysts

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

• yields, indicating potential utility in chiral fluorescent materials. In addition, Du’s group reported an N-heterocyclic carbene (NHC)-catalyzed (3 + 3) cycloaddition of 2,6-disubstituted alkyne esters 38 with 6-aminouracils 39, affording distal biaxial uracil frameworks with both C–C and C–N chiral axes

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

• Maryna V. Kachaeva Agnieszka B. Olejniczak Marta Denel-Bobrowska Victor V. Zhirnov Yevheniia S. Velihina Stepan G. Pilyo Volodymyr S. Brovarets Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, National

• oxazolopyrimidine derivatives may demonstrate selective cytotoxicity against cancer cell lines like HeLa, HepG2, A549, and central nervous system (CNS) tumor models [1][2][3]. The introduction of heterocyclic molecules with different amino groups as hydrogen-bond donors (and sometimes acceptors via lone electron

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• equivalents of LiHMDS, N-alkyl- and N-arylanilides were efficiently cleaved to afford the corresponding amides 64 and 162–165 in high yields. A broad range of N,N-dialkylamides, cyclic amides, and heterocyclic amides were also compatible, all delivering amide products 3, 4, and 166–172 in good to excellent

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

• -2-ethynylpyrrolidine-1-oxyls with nucleophilic agents can lead to the formation of condensed systems involving the substituent at position 3 of the pyrrolidine ring [16]. Alkynes are broadly used in the synthesis of various heterocyclic compounds, and participation of neighboring functional groups

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

• system of two condensed pyrrolidine rings sharing a common nitrogen atom. This heterocyclic system occurs naturally in numerous plant-derived alkaloids [27][28][29][30]. Notably, most pyrrolizidine alkaloids exhibit severe hepatotoxicity, genotoxicity and cause neurological disorders in humans and

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• , affording the corresponding sulfinimidate esters 3j’ and 3k’ in excellent yields. Notably, a pyrazine-2-carboxamide-derived sulfenamide also underwent efficient transformation to 3l’, further highlighting the method’s functional group compatibility and applicability to heterocyclic systems. We further

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• cyanide and the chemosensor is determined by a 1H NMR study and explained by DFT calculations. Keywords: chemosensor; DFT calculations; donor–π–acceptor–π–donor based organic dyes; indan-2-one; NLO; Introduction Over the past decades, the functional heterocyclic push–pull dyes have attracted significant

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• cyanoacetate, ethyl cyanoacetate, benzoylacetonitrile), carbocyclic (1,3-indanedione), and heterocyclic (Meldrum’s acid, dimethylbarbituric acid, 3-methyl-1-phenyl-5-pyrazolone) CH-acids – allows the synthesis of both monocyclic and spirocyclic 1SR,2RS vic-trichloromethylnitrocyclopropanes under mild

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

• highlights representative examples that illustrate recent synthetic advances [35][36]. Hydrogenation of monocyclic aromatic rings Hydrogenation of heterocyclic aromatic rings: Despite the widespread application of six-membered aromatic heterocycles in various fields of organic chemistry, reports on their

• catalyst to achieve the hydrogenation of the nitrogen heterocyclic moiety in quinoline, that yielded the target product in near-quantitative amounts [51]. In 2021, the research groups of Sun [52] and Zhang [53] reported the use of iridium or manganese as catalysts to convert quinoline derivatives into

• new stereocenters, producing architecturally complex 6–5 fused ring systems. The key points lie in the utility of a chiral homogeneous ruthenium-N-heterocyclic carbene complex, as well as an in-situ activated rhodium catalyst. In 2022, Bach and co-workers reported a modular approach for the highly

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

• , generated via borocupration of terminal alkynes, underwent allylic substitutions to furnish Bpin-substituted alkenyl chlorides in high enantioselectivity (Scheme 65B) [204]. Key to the transformation was the use of a sulfonate-substituted N-heterocyclic carbene ligand, introduced as its imidazolium salt

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• particular interest for the regioselective synthesis of azoxy compounds [5][71][72]. Unique and understudied representatives of the latter are nitro-NNO-azoxy compounds [R–N(O)=N–NO2], first synthesized at ZIOC RAS [73][74][75]. Nowadays, aromatic and heterocyclic compounds of this class have been studied in

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• , respectively. The introduction of cycloketones has resulted in the same types of heterocyclic systems, yet they are now carboannelated, which are synthetic analogues of alkaloids [26]. Moreover, it has been shown that acetaldehyde is capable of reacting in a similar manner with ethyl trifluoroacetoacetate and

• ]. In general, the developed approach allows pyridone derivatives to be generated in various environments of condensed carbo- and heterocyclic structures. Among the synthesized pyridone derivatives we have found analgesic [20][26], antibacterial [20] and antifungal [20] agents, which show practical

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

• available drugs [1]. These structures exhibit unique properties that influence pharmacokinetic and pharmacodynamic parameters, including lipophilicity, polarity, hydrogen-bonding capacity, and toxicological profiles [2][3][4]. Among them, five-membered multi-heterocyclic (FMMH) rings are privileged

• heterocyclic aldehydes such as furfural (3v), thiophene (3w) and indole (3x) carboxaldehydes. Application of the optimized EDA-catalyzed Knoevenagel conditions to thiazolidine-2,4-dione (2b) afforded the expected product 4a in moderate yield (Supporting Information File 1, Table S1). Adding excess thiazolidine

• condensation reactions involving rhodanine derivatives (26 examples). In addition, it requires a lower catalyst loading (10 mol %) and eliminates the need for further purification steps. EDDA has also been employed in reactions for the synthesis of heterocyclic compounds such as tetrahydroquinolines [67

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• chemistry. In particular, dual catalysis combining N-heterocyclic carbenes (NHCs) with organophotocatalysts (e.g., 4CzIPN, eosin Y, rhodamine, 3DPAFIPN, Mes-Acr-Me+ClO4−) has emerged as a powerful photocatalytic strategy for efficiently constructing a wide variety of carbonyl compounds via radical cross

• , particularly the synergistic combination of N-heterocyclic carbenes (NHCs) with organic photocatalysts, has opened new avenues in molecular construction, particularly for the novel, practical preparation of carbonyl group-containing compounds [13][14][15][16]. These ubiquitous ketone, ester, and amide

• functional groups are found in various drugs, natural products, and optoelectronic materials. In the last three decades, N-heterocyclic carbenes (NHCs) have been renowned as versatile organocatalysts, including thiazolium, imidazolium, and triazolium moieties. NHCs are extensively used in many catalytic