Rhodopyran, a carboxylated hexahydrocyclopenta[b]pyran from Rhodococcus

• Enjuro Harunari,
• Sara Fushimi and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2026, 22, 1107–1113, doi:10.3762/bjoc.22.89

• possess distinct architectures such as spirocyclic motifs or three-membered rings. Collectively, these observations suggest that the natural product chemical space of this structural class remains largely unexplored, and underscore that pursuing genome mining in parallel with cultivation-based screening

Semisynthesis, characterisation, and antibacterial evaluation of a novel lecanoric acid-derived amide library

• Ethan D. Abbott,
• Sasha Hayes,
• Jonathan M. White,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 1023–1032, doi:10.3762/bjoc.22.81

• metabolites that included divaricatic acid (2), orcinol (3), orsellinic acid (4), and methyl orsellinate (5). Parallel solution-phase synthesis using amidation chemistry on the abundant scaffold 1 afforded a series of novel amide derivatives 6–13 in high purity (>95%) and low to moderate yields (12–53%). All

The role of spacer length and flexibility in peptide self-assembly

• Julian Link,
• Albin Lahu,
• Manfred Wagner,
• Tanja Weil and
• David Y. W. Ng

Beilstein J. Org. Chem. 2026, 22, 986–996, doi:10.3762/bjoc.22.77

•  1A) [40]. The peptide stock solutions prepared in TFE (10 mM) were diluted in PBS (50 mM, pH 7.4) to obtain 100 µM peptide samples (1% TFE). The mixtures were then incubated at room temperature for 24 h to promote self-assembly. Corresponding samples in methanol (1% TFE) were prepared in parallel and

Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies

• Antonio Angelastro,
• Jonathan Bargh,
• Subhajit Guria,
• Victor Laserna and
• Louis Luk

Beilstein J. Org. Chem. 2026, 22, 857–881, doi:10.3762/bjoc.22.67

• strong potential to generate novel biotherapeutics. As the development of protein-based therapeutics and diagnostics continues to expand to address global health challenges, the demand for tailored protein-modification strategies is increasing in parallel. Indeed, protein-modification chemistry is a key

Synthesis and structural elucidation of a novel bis-spirooxindole from isatin and ethylenediamine

• Irene Moreno-Gutiérrez,
• Josefa L. López-Martínez,
• Sonia Berenguel-Gómez,
• Irene Torres-García,
• Duane Choquesillo-Lazarte,
• Manuel Muñoz-Dorado,
• Miriam Álvarez-Corral and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2026, 22, 813–820, doi:10.3762/bjoc.22.63

• conditions. Keywords: ethylenediamine; isatin; spirooxindole; Introduction Isatin (1) is a highly versatile platform for heterocycle construction, particularly through skeletal editing, ring expansion, and related transformations that enable rapid access to complex molecular architectures [1]. In parallel

Halogenated azobenzene acrylates: from efficient solution photoswitching to stable solid-state photochromic materials

• Martina Vachtlová,
• Michaela Fecková,
• Vítězslav Zima,
• Jan Podlesný,
• Milan Klikar,
• Oldřich Pytela,
• Patrik Pařík,
• Jakub Opršal,
• Eliška Juhaňáková,
• Veronika Chrtová and
• Filip Bureš

Beilstein J. Org. Chem. 2026, 22, 782–794, doi:10.3762/bjoc.22.60

• approximate ratio of ipred1,cat vs ipox1,an = 1:3 for compounds 1a–e. This indicates a three-electron process within the first oxidation, implying parallel oxidation of the “phenolic” oxygen and the adjacent π-system. The mutual ratio of both current maxima was more balanced in the case of the dibromo

Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators

• Xi Zhang,
• Jingyan Wang,
• Ziqiang Zhao,
• Caiyi Wang,
• Zenghui Ye,
• Wei-Yuan Ma,
• Jian-Xing Xu and
• Fengzhi Zhang

Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59

• ; Introduction The pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD) is characterized by multifactorial interactions between environmental, genetic, extrahepatic, and intrahepatic factors. These factors can act in a parallel or sequential manner to drive the development of steatosis

Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• bonds in TS-trans, there is a significant distortion in the chair shape in TS-cis: the two highlighted CH bonds are not parallel – they are converging and this 1,3-diaxial interaction may be a contributing factor in increasing the activation barrier relative to TS-trans. Further technical discussion of

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

• 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

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

• eventual deprotection of the Piv-moiety, followed by DMP-oxidation led to the formation of the target fragment 292. In parallel, 296 was synthesized via Cr(III)-catalyzed coupling of aldehyde 294 with diiodide 171 (see Scheme 17) and subsequent mesylation (Scheme 33). Stereoselective Cr(II)-catalyzed

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

• [41]. This strategy delivered excellent enantioselectivity, diastereoselectivity, and overall efficiency, underscoring its unique advantages in the synthesis of multiaxially chiral scaffolds. In parallel, Tanaka and co-workers advanced a [2 + 2 + 2] cycloaddition strategy to realize an asymmetric

• axially chiral bridged teraryl molecules 34 (Scheme 9) [50]. This method provided access to biaxial bridged eight-membered terphenyl atropisomers with broad substrate scope, high yields, and operational simplicity under air. In parallel, Shi’s group developed a cobalt-catalyzed asymmetric synthesis of

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

• characteristic transformations of the organosulfur functionality [32][33]. In 2024, Badani, Karnik, and co-workers accessed one member of this class, 7,12-dioxa[8]helicene I, through a sequence featuring photochemical E–Z isomerization, electrocyclization, and oxidative aromatization [34]. In parallel, Liu and

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

• coupled with cooperative alkali metal counter cations, have expanded the scope of amide C–N bond cleavage under mild conditions. In parallel, the installation of activating groups on the amide nitrogen has enabled chemoselective cleavage, opening the door to late-stage transformations of target amides

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

• ], allylgrignards [78], amines [79], and allenylstannanes [80], thereby accessing the corresponding propargyl-functionalized products (Scheme 6B). In parallel, Bao and co-workers demonstrated that the dearomatization manifold extends beyond simple benzenoid systems to include heteroarenes such as furans, thiophenes

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

• cycles and enables the parallel exploration of diverse chemical space. The impact of MCRs is well documented in medicinal chemistry and pharmaceutical research, including the development of several approved drugs [14][15][16][17][18]. Recently, 4-hydroxyquinoline-2(1H)-ones and their derivatives have

• undergoes Michael addition to arylidene intermediate C. The thus formed adduct D is protonated by ʟ-proline and undergoes tautomerization. During the initial experiments to synthesizing methyl and ethyl esters via this four-component reaction, we observed the parallel formation of an undesired cyclic

Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• , the peri-functionalization approach paved a new pathway for the generation of chiral helical molecules. In this article, we highlight the key advancements in these parallel approaches for the generation of helical chiral architectures. Keywords: catalysis; C–H functionalization; helical chirality

• approaches have been developed for the synthesis of chiral helical molecules and the most prevalent approaches include cycloaddition reactions [24], ring extensions [25], and related approaches [26][27]. However, some parallel and more sustainable approaches have emerged in recent years and C–H

• functionalizations are one of these approaches. In the following section, we discuss the parallel approaches, i.e., peri-C–H functionalization, over the prevalent approach for the generation of helical chirality, which generally considers π extension. The peri-C–H functionalization approach provides direct access to

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

• intermediate 196, which was further elaborated over seven steps (overall yield: 74%) to give 197. In parallel, the authors adopted Glorius’ protocol, applying an Evans chiral auxiliary to achieve asymmetric catalytic hydrogenation of the pyridine derivative 198, delivering the lactam 199 in 66% yield and with

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

• one equivalent of N-methylimidazole (NMI) (Scheme 54A) [183]. However, the reaction still resulted in 3–25% yield of the dialkylated product. Consequently, the reaction conditions required adaptation for each substrate to maximize the yield of the monoalkylated product. In a parallel work, Barluenga

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• ). Further geometrical adjustment and conformational restriction of the transient structure enable the N9 nonbonding p orbital to align parallel to the σ(C19–C3)* orbital (Figure 2f, TS2 → F-10 → F-40 → IN3), which reinforces the hyperconjugative interaction. Facilitated by the bond stretching and bond-angle

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• between 10 µM and 30 µM, and poor under 10 µM. Compounds with no value were under the detection limit. As a result, seven compounds had good solubilities: (E)-7c, (Z)-7c, 7d, 7e, 3b, 3c, and 3e. We also carried out a gastrointestinal parallel artificial membrane permeability assay (GI PAMPA). The

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• synthesis of amines by replacing the current toxic pathway based on ethylene oxide and dichloroethane [29]. Due to the high reactivity of α-hydroxycarbonyls, the main issue in this reductive amination reaction [30] was to control the cascade of consecutive and parallel reactions. The use of methanol as

• ][87][88][89][90][91][92]. Essayem and co-workers reported the conversion of DHA with the help of TiO2-based catalysts having dual properties. Two parallel pathways are as follows: on one hand the catalyst Lewis acidic sites promote the formation of pyruvaldehyde and lactic acid (LA) by a two-step

Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• similar compounds based on 5-amino-1H-pyrazole-4-carbonitrile [22]. It should be noted that diazocines 4 were stable and did not undergo transformations when heated or irradiated with ultrasound. This may indicate that pyrimidine-7-carboxylic acids 5 and 6 are formed in parallel processes under kinetic

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• coplanar with a dihedral angle of 170°. The two dichlorobenzene rings are parallel to each other and perpendicular to the pyrene plane, and the four tert-butylphenyl groups are directed on one side of the pyrene plane to minimize steric repulsion. MC2 takes a C2v-symmetric saddle-shaped geometry with two

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• -diimines. Later, in 2001, Yudin and co-workers described the parallel reductive coupling of aldimines using a spatially addressable electrosynthesis platform, which employed a stainless steel cathode, a sacrificial aluminum anode and a procedure adapted from Torii's earlier work including the use of PbBr2

• , TFA, and Bu4NBr [45]. Under these conditions, parallel electrosynthesis allowed the synthesis of up to 16 vicinal diamines in good yields in 30 minutes. To the best of our knowledge, the most recent example of electroreductive coupling of imines was reported in 2025 by Wang’s research group [46], who

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• antiparallel conformation (Scheme 41). However, open-ring diarylethenes usually consist of an equilibrium between a parallel conformation (not active) and antiparallel (active). For some examples, the equilibrium was also found to be affected by the polarity of the solvent: polar solvents could stabilise the

• parallel excited state because of the larger dipole moment [121]. To enrich the population of the antiparallel (and thus increasing the quantum yield of cyclisation), bulky substituents on the 2,2’ positions of benzothiophene were added [122], also the antiparallel conformation could be fixed by