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

• efficient macrocyclization methods, including tetracarbonylnickel-promoted cyclization of allylic dibromide [17][18], copper-mediated intramolecular carbene–olefin cyclization [19], titanium-induced intramolecular carbonyl coupling [20], and organozinc carbenoid-mediated intramolecular cyclopropanation [21

• . With the ability to facilely obtain the terpene skeletons such as casbene and germacrene A by this heterologous terpene-producing platform, accessing other casbane- and germacrene-type of natural products and their analogues becomes possible if suitable chemical and enzymatic methods are available for

• ). Supporting Information Supporting Information File 5: Materials, synthetic methods and copies of NMR spectra for all compounds. Supporting Information File 6: X-ray crystal structure of 16. Funding We are grateful to the National Natural Science Foundation of China (No. 82574274) for the financial support.

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

• a key property for characterizing the light harnessing efficiency of a photoswitch. In the article by Volker, Steen, and Crespi [18], a convenient and reliable fiber optic spectroscopic setup for determining this quantum yield is reported and was benchmarked for azobenzene against other methods

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

• experimental co-crystal structure of the bound complex, standard medicinal chemistry principles are used to probe structure–activity relationships (SAR) and determine the key interactions that form a minimal pharmacophore, supported by classical physics-based molecular modelling methods such as molecular

• candidate small molecules for experimental validation in functional assays. Nascent examples of ML approaches In contrast to physics-based models for extracting pharmacophores and predicting small molecule binders, ML methods are now emerging as alternatives for accomplishing these tasks. An early

• tractable, although synthetic accessibility was noted to be somewhat restricted by the highly sp3-rich nature of the generated molecules. New iterations of these methods have since been reported by the authors [23], though experimental validation of predictions remains to be reported at the time of writing

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

• approaches can be regarded as among the most environmentally sustainable methods for trifluoromethylation. MacMillan and co-workers reported the photochemical trifluoromethylation of arenes and heteroarenes using Ru- and Ir-based photocatalysts together with trifluoromethanesulfonyl chloride (TfCl) in the

Computational prediction of C–H hydricities and their use in predicting the regioselectivity of electron-rich C–H functionalisation reactions

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2026, 22, 603–610, doi:10.3762/bjoc.22.46

• electron-rich C–H functionalisation reactions. Methods Datasets To validate our QM workflow, we use a dataset of 35 experimental C–H hydricities in dimethyl sulfoxide (DMSO, 26 compounds) and acetonitrile (MeCN, 9 compounds) from Parker and co-workers [7]. As 35 C–H hydricities are insufficient to train an

• that evaluates the accuracy of different levels of theory, ranging from semiempirical methods (xTB [16]), composite electronic structure methods (r2SCAN-3c [19]) to DFT methods (M06-2X[21], CAM-B3LYP [22][23]). All methods are evaluated either as single-point calculations or optimization and frequency

• predictive accuracy for sterically demanding carbene insertion reactions, where all current methods underperform. While the ten literature examples discussed here provide promising proof-of-concept evidence, establishing the general utility of hydricity for regioselectivity prediction will require validation

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

• strategies to combat the antibiotic resistance include, in particular, the synthesis of novel antibacterial agents based on isoxazole derivatives [17]. In this regards, the development of efficient and convenient methods for the sulfonyl-containing isoxazoles synthesis has received great attention. The most

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

• as functional materials and pharmaceuticals [1][2][3][4]. While stoichiometric reagents and catalytic methods are widely developed for this transformation, one of the most ideal methods is heterogeneous catalysis using molecular hydrogen as a reductant, which realizes 100% atom economy [5][6][7][8][9

• ][10][11][12]. In this context, advanced technologies represented by the precise control of the bimetallic structure of a heterogeneous catalyst, mechanochemical hydrogenation, and continuous-flow methods using packed-bed reactors greatly contributed to advancing this transformation [9][11][12][13

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

• . Supporting Information Supporting Information File 16: Experimental part. Acknowledgements We acknowledge important conceptual help and generous support with methods and instruments from the group of Andrea Musacchio at the Max-Planck-Institute of Molecular Physiology, Dortmund. Funding CG, PR, CB, PB, DB

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

• in the mixture of melifoliones was increased to a maximum of about 10–15%. Since it was not possible to distinguish or even to separate the isomeric melifoliones using chromatographic methods, their quantitative ratio after cyclization of 5 could only be determined using the 1H NMR spectra. After

• and data acquisition. Data collection was therefore applied with seriously elongated exposure time. The crystal structure was successfully solved using methods as implemented in the SHELXT program [16], followed by refinement with SHELXL [17]. The refined asymmetric unit was found to contain about

• from mixtures of melifoliones 1 and 2 using the applied chemical methods. Thus, it is clearly proven, that 4 cannot be built as an artifact during the isolation. Therefore, it is likely that the biosynthesis of the quinol 4 occurs via enzymatically catalysed oxidation in the leaves of Melicope

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

• are not necessarily consecutive and may not be readily dissected. Furthermore, as the reaction intermediates are isomers with mainly similar structural fragments, it is difficult to distinguish them by the usually employed spectroscopic methods because of overlapping signals [22][30][33]. Along these

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

• using CrCl3 and NbCpCl4. The last steps towards 1 are known procedures [68]. By comparison to former methods, this technique does not require further desulfonylation after the macrocyclization [19][68]. Choi and co-workers used a previously reported protocol on stereo- and regioselective allene-Prins

• the targeted derivatization of 1 for future works [110]. An overview of methods, including the respective fragments, steps and scales, is shown in Table 1. Given the importance of 1 for medicine and the reasearch interest in 1`s derivatives to potentially enhance its potency, this research field will

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

• carboxylic acid derivatives such as esters, acyl chlorides and anhydrides with hydroxylamine salts [41]. A variety of coupling or activating agents were also employed in case of simple addition of hydroxylamine to carboxylic acid compounds [42][43][44]. In addition, alternative methods starting from

• , following the method reported by Camiolo and Gale [21], affording a yield of 85%. Among several procedures used for the direct hydroxyaminolysis of carboxylic ester substrates, Beillard et al. highlighted the superiority of a DBU (1,8-diazabicyclo[5.4.0]undec-7-ene)-mediated route over the classical methods

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

• has been partially summarized in existing reviews [38][39]. This article aims to provide a comprehensive overview of reported methods for the synthesis of remote biaxial chiral molecules, focusing on three main synthetic strategies: direct one-step synthesis of biaxial systems, sequential formation of

• in catalysis, drug discovery, and functional materials. Review One-step construction of remote biaxial chiral molecules In recent years, the development of asymmetric catalytic methods, including both transition-metal catalysis and organocatalysis, has provided powerful tools for the one-step

• exceeding 60%. Sequential construction of distal biaxial chirality via stepwise axis formation Although one-step catalytic methods enable the efficient and direct construction of remote biaxially chiral molecules, the spatial interactions between multiple chiral axes can make it challenging to fully control

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

• 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

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

• carried out under a nitrogen atmosphere using standard Schlenk line methods. Reagents and solvents were obtained from GK Life Sciences Pvt. Ltd. and used without further purification unless otherwise stated. Thin-layer chromatography (TLC) was performed on silica-gel-coated aluminium sheets (silica gel 60

• docking with selenium-containing ligands, the parameter file (AD4.1_bound.dat) was included. The resulting protein–ligand interactions were analysed using Discovery Studio Visualizer. Biological methods Cell culture The National Centre for Cell Science (NCCS), located in Pune, India, provided the MDA-MB

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

• described methods [14][15][16] as depicted in Scheme 2. The 7-Amino-substituted 1,3-oxazolo[4,5-d]pyrimidines 1–9 were obtained with high yields (65–80%) by the reaction of 2,5-diaryl-7-chloro-1,3-oxazolo[4,5-d]pyrimidines II with the corresponding amine (aminoethylamines [17], cytisine and N-methyl-ᴅ

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

• field is offering diverse methodologies that enable the introduction of either protected nitrogen atoms or aliphatic amine groups. Such diversity has greatly expanded the synthetic arsenal available for constructing aminomethylated compounds. In contrast, methods allowing an aminoethylation process is

• 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

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

• ]helicenes. Inspired by the superior selectivity and sustainability of organic electrosynthesis as an eco-friendly alternative to conventional oxidative methods [43][44][45][46][47], we leveraged our electrochemical approaches [48][49][50][51][52], and redesigned the synthons to access a new unsymmetrical

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

• valuable features, amide derivatives are ubiquitous across the pharmaceutical, agrochemical, dye, polymer, and renewable-energy industries [6][7][8][9][10][11]. Accordingly, the development of efficient methods for both amide-bond formation and the selective transformation of amide functionalities remains

• , such methods often exhibit limited substrate scope, generally restricted to amides with low steric hindrance, such as DMF or DMAC. In recent years, several new strategies have emerged to overcome these limitations: (i) transition-metal-free activation using electrophilic reagents, (ii) strong-base

• employed as reliable tools to activate amide bonds through coordination with the amide oxygen lone pair [45]. Although the substrate scope of such methods remains limited, several successful examples with hindered amides have recently been reported. In 2019, Shimizu et al. reported the esterification of

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

• barbiturates [25]. Other methods include the DBU-mediated stereospecific cyclopropanation of barbiturate-based olefins with benzyl chlorides, developed by Chang’s group for the synthesis of spirobarbiturate-cyclopropanes [26]. Another interesting structural fragment is the pyrrolizidine heterocycle, which is a

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• ]. Today, aromatic compounds are essential in both academic and industrial chemical applications (Figure 1B) [9][10]. Their ubiquity is the result of a decades-spanning effort devoted to leveraging aromatic stability in the development of methods that functionalize the periphery of arenes without

• aromaticity and unveiling the latent double-bond character within the aromatic ring. This dramatically increases reactivity, enabling alkene-like transformations with aromatic molecules that are inaccessible by conventional synthetic methods, thereby complementing traditional arene chemistry. Other modes of

• , enabling transformations that were previously inaccessible through conventional methods. Beyond their mechanistic elegance, these systems have demonstrated tangible utility in constructing complex molecular architectures with high precision. However, a key obstacle to the broader use of η2-coordinating

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

• ; Introduction Contemporary organic chemistry focuses on the development of universal, efficient, and environmentally benign synthetic methods that address the challenges of constructing complex molecular architectures [1][2][3]. Among these, multicomponent reactions (MCRs) have emerged as powerful tools

• eluents. Among these methods, in situ acyl chloride formation using thionyl chloride in the presence of DMF in 1,2-dichloroethane is advantageous due to low cost, straightforward reaction handling, high yields, and product purity. After a short reaction time, triethylamine was added, affording

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• effect are expected to play a decisive role in determining the bioactive conformation and, consequently, the molecular bioactivity. Methods A stochastic conformational search of (S)-DFMO was performed at the semiempirical AM1 level [26] using the Spartan program [27]. The Monte Carlo algorithm employed

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

• methods for phosphorus chemicals that do not depend on white phosphorus or phosphorus chloride have been developed to reduce energy consumption and environmental hazards. For example, Montchamp’s group and Yang’s group have focused on using sodium phosphinate as an alternative to PCl3, and various halogen

• -free synthetic methods have been reported for the synthesis of phosphorus compounds (Figure 2A) [35][36][37][38][39][40][41]. Cummins’s group demonstrated that phosphoric acid and condensed phosphoric acid can be reduced using trichlorosilane. The resulting intermediate, the bis(trichlorosilyl

• standard curve was constructed using potassium dihydrogen phosphate solutions (0.5, 1.0, and 1.5 µg P/mL) as the standard solutions. Diaryl phosphate synthesis and characterization The synthesis methods for diaryl phosphates using commercial and extracted phytic acid are included in Supporting Information

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• migration in the formed tetrahedral intermediate to afford formate ester; c) hydrolysis of the latter to form phenols [28]. The development of methods for the construction of heterocycles and their modification is an important area of organic synthesis [29]. Although the Dakin oxidation has become a