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

• transformations [3][4]. However, the limited abundance of free cysteine residues in proteins has driven the development of alternative approaches targeting other chemical motifs. This review summarizes current strategies for site-specific modifications of these alternative sites, followed by a comparative

• ) refer to chemical changes to a protein in-cell after it is synthesised by the ribosome, encompassing over 650 types of transformations, including phosphorylation, methylation, acylation, ubiquitination and glycosylation [110]. While numerous naturally occurring PTMs have been repurposed for

The trans-influence in gold chemistry from a catalytic perspective

• Manfred Bochmann

Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66

• recent mechanistic insights. Keywords: catalysis; gold; ligands; reaction mechanism; trans-influence; Introduction Gold catalysts have emerged as catalysts of choice in a multitude of organic transformations, not least due to their high functional group tolerance. Their applications have been widely

Unsymmetrical sulfoxides with sterically hindered catechol fragment: synthesis, structure, electrochemical properties, and antiradical activity

• Daria A. Burmistrova,
• Vasiliy A. Fokin,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Maxim V. Arsenyev,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2026, 22, 828–837, doi:10.3762/bjoc.22.65

• on the sulfoxide group. Keywords: antioxidant activity; catechol thioethers; redox-transformations; sulfoxides; X-ray analysis; Introduction Polyphenolic compounds can participate in redox processes and undergo a wide range of chemical modifications. As a result, they possess diverse biological

• 1.82–1.91 V. The value of Epox2 for the above-mentioned compounds is shifted anodically by 0.26–0.31 V relative to the corresponding thioethers, reflecting an increase in the Gibbs free energy (ΔG) of the electrooxidation process by 12–15 kcal/mol. Redox transformations at the sulfur atom occur in

• either one or two stages, depending on the degree of branching of the hydrocarbon substituent. A possible mechanism for the anodic transformations of sulfoxides is the two-electron oxidation of the substituted o-benzoquinone formed in the first stage to a dication (Scheme 2, path a). Further

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

Synthetic study of vic-bromination of diarylacetylenes, easy purification and separation

• Akane Togo,
• Hiyono Suzuki,
• Yuto Akai,
• Makoto Matsumoto,
• Yoshinori Suzuma,
• Hidehiko Kodama and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2026, 22, 795–802, doi:10.3762/bjoc.22.61

• ; Introduction The addition reaction of bromine to diphenylacetylene is one of basic reactions and is recognized as important, because resulting 1,2-dibromo-1,2-diphenylethylene can serve as a precursor for various molecular transformations in organic synthesis [1][2]. This reaction seems to be simple, but some

• interested in the selective synthesis of the E isomer of 1,2-dibromo-1,2-diphenylethylene, together with simple purification and separation toward process chemistry, because the compound is an attractive synthetic intermediate for further transformations. During the course of our studies, we have found that

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

• heterocycles and also those looking to use Rongalite as a source of nucleophilic sulfur in other transformations. We are currently examining extensions of this method and other sulfinate reaction development and catalysis. Rongalite as an equivalent of the unstable hyposulfite ion. Sulfone diastereomers 1a and

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

• , the importance of the formation of azomethine ylides from amino esters, amino acids, imine derivatives, aziridines or other substrates was emphasized. A review [26] demonstrates metal-catalyzed as well as metal-free asymmetric and racemic transformations of imino ethers upon interaction with various

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

• trifluoromethyl-substituted compounds. Over the past decade, numerous photocatalytic protocols for the trifluoromethylation of arenes and heteroarenes have been developed, including approaches employing microflow techniques [6]. These transformations utilize a broad spectrum of catalysts, ranging from Ru- and Ir

• -catalyzed [8], organic photocatalyst-mediated, or electrochemical transformations [9], and also include continuous-flow processes [6][10][11][12][13]. Given that photocatalytic reactions align with the principles of green chemistry, particularly energy efficiency and the use of catalytic pathways, such

• transformations were performed in acetonitrile, which reduces their ecological compatibility, particularly for large-scale applications. Tlili and co-workers have described the use of an organic photocatalyst for the CF3-functionalization of styrenes with the Langlois reagent (sodium trifluoromethanesulfinate

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

• –N, C–C, and C–X bond formations, carbene insertions, and oxidative transformations. Comparative analysis with ALFABET, a bond dissociation energy (BDE)-based ML model, reveals that hydricity predictions, when combined with steric accessibility, correctly identify the reactive site in eight out of

• one of the most common C–H functionalisation approaches for sp3 C–H bonds [6]. Despite the prevalence of these transformations, predicting which of several electron-rich C–H sites will react remains challenging, especially when electronic and steric effects compete. As Cernak et al. [6] have pointed

• ). Many of these transformations are not formal hydride transfers; however, they commonly involve buildup of positive charge (e.g., via metal–carbene/nitrene insertion transition states, radical cations, or polar hydrogen atom transfer). Hydricity could therefore serve here as an empirical reactivity

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

• cyclization proved to be suitable, but only moderately yielding, procedures. Further, this pathway, with the exception of the coupling reaction between 167 and 171, involves only simple and mild transformations using standard reagents. As mentioned above, 186 served as an intermediate for the total synthesis

• thereafter, Nasam and co-workers developed a novel synthesis of 1`s fragment 272 using multiple asymmetric catalytic transformations (Schemes 29–31) [102]. 256 was synthesized from trans-crotonic acid and served as a starting material for the first building block (261, Scheme 29). Hosomi–Sakurai allylation

• sequence of 12 steps, which only included the use of cheap materials and preparatively simple transformations. Therefore, if the overall yield can be increased even further, this synthesis represents a useful alternative to existing pathways. Conclusion In summary, numerous advancements were made in 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

• induce axial chirality. In this approach, the initial formation of one or more stereogenic centers establishes a defined three-dimensional framework, which subsequently guides the generation of one or more chiral axes through cyclization, oxidative aromatization, or related transformations. This central

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

• (vibralactone, Zhi-Yun Liu, Hong-Dong Hao et al.), interrupted [2 + 2]/retro-Mannich (aspidosperma alkaloids, Zhen Yang, Zhong-Chao Zhang et al.), dipolar cycloaddition (malayamycin A, Sha-Hua Huang, Jian Jin, Ran Hong, et al.), Zr-mediated radical transformations (review, Hugh Nakamura and co-worker)]. The

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

• tetraureacalix[4]arenes was obtained. Examination of the 1H NMR spectra of the tetraureas in CDCl3 showed that in most cases triazole heterocycles do not intervene the formation of homo- and heterodimeric capsules by these compounds. Thus, considering the synthetic value of CuAAC and amine transformations, p

• 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

• compatible with propargyl or 2-azidoethyl functionalities residing at the calixarene narrow rims, these ‘simple’ transformations are not applicable to the available propargylated/2-azidoethylated p-tert-butyl- or p-H-calix[4]arenes. Therefore, the multistep reaction sequences presented below have been

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

• ]. Such activation has enabled a wide array of transformations, including metal-catalyzed cross-couplings via oxidative addition into the amide C–N bond (Scheme 1c) [32][33][34][35][36], and transition-metal-free acyl substitutions facilitated by improved leaving-group ability [37][38][39][40]. Although

• -promoted transformations enhanced by alkali-metal counter-cation effects, and (iii) installation of activating groups on the nitrogen to enable chemoselective cleavage under tailored conditions. These approaches collectively offer promising avenues for the efficient transformation of non-activated amides

• activation assisted by alkali metal counter cations Although strong bases can promote nucleophilic transformations of amides, such reactions have traditionally required harsh conditions [69][70]. Recently, however, the role of alkali metal counter cations in facilitating acyl substitution has been recognized

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• secured. Organic synthetic chemistry can help to fill gaps or evaluate, support or revise initially implausible proposed biogenesis routes by attempting to mimic these transformations (= bioinspired or biomimetic synthesis) [11][12][13][14][15][16][17][18]. In general, the biogenesis of unique carbon

• Moving on from these carefully characterised biosynthetic transformations, where often single steps were carried out with specific enzymes or isotope-labelled substrates to prove origin, we now move to the much larger body of speculative biosynthetic relationships. From macrocyclic lathyrane frameworks

• previous studies, no detailed studies on the transformations connecting all these families have been performed thus far [133][134][135][136]. Novel Euphorbia diterpenoids recently isolated by Wang, Zheng and Yu in 2024 (see Scheme 23A) could be considered “missing links” offering an explanation as to how

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

• transformations for the synthesis of complex, three-dimensional molecular architectures with tailored physicochemical properties. Despite notable advances in dearomative methodologies over the past decades, the selective and controlled disruption of the aromatic core continues to represent a fundamental challenge

• disrupting the aromatic core, such as electrophilic and nucleophilic aromatic substitutions, transition metal-catalyzed cross-couplings [11], and C–H functionalizations [12]. Taken together with their natural abundance, these transformations have established arenes and heteroarenes as versatile synthetic

• 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

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

• acids followed by sequential Michael-type addition and subsequent cascade transformations. This versatile one-pot protocol delivers structurally diverse open-chain 3-arylpropanoate esters in moderate to good yields (46–69%), while cyclic pyranoquinolinones are formed under kinetically controlled

• conditions. Subsequent transformations afford isopropyl and cyclohexyl analogues via hydrolysis–esterification. A preliminary biological evaluation revealed low cytotoxicity and modest antibacterial activity against Escherichia coli ΔtolC strains. This sustainable synthetic approach constitutes the first

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

• substitution pattern along the plane of symmetry, is known as planar chirality, as seen in metallocene and cyclophanes. Molecules containing planar chirality have greater relevance in materials science and stereoselective transformations [12][13]. The fourth branch of the chiral tree is helical chirality. A

• further transformed into representative derivatives. Notably, the reaction performed well in the scale-up demonstration and the post-synthetic transformations proceeded smoothly without hampering the enantiomeric excess (Scheme 2). Another report applying peri-C–H functionalization for the synthesis of

• enantiomeric excess and diastereomeric ratio (Scheme 3). The developed protocol was also tested for up-scale synthesis and post-synthetic transformations. Notably, the reaction worked well at a 4.0 mmol scale providing product 8g in quantitative yield and >99% ee. This product was further reduced to the

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

• , Leuven B-3001, Belgium 10.3762/bjoc.22.13 Abstract Solvent-dependent transformations of polysubstituted 2-acetyl-2,5-dihydrothiophenes to the corresponding 2-hydroxy- or deacetylated derivatives are described. The treatment of a methanolic solution of the dihydrothiophene substrates with sodium

• methoxide afforded the deacylated products. Conversely, the treatment with sodium ethoxide in an oxygen saturated ethanolic solution produced 2-hydroxy substituted 2,5-dihydrothiophenes. Keywords: 2-acetyl-2,5-dihydrothiophenes; deacylation; 2-hydroxy-2,5-dihydrothiophenes; transformations; Introduction

• Oxidative transformations are an important area of modern organic synthesis [1], producing a broad range of valuable synthetic products for the industry. A variety of catalytic reactions were developed for the oxidative conversions of unsaturated compounds [2][3][4][5], alcohols [6][7], alkanes [8][9][10

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

• , such transformations remain synthetically challenging. This is primarily due to the well-known Mukaiyama-type oxidation, wherein sulfenamides serve as redox catalysts for NBS- or NCS-mediated oxidations of alcohols to aldehydes or ketones (Scheme 1b, top) [38][39][40][41][42]. Under such oxidative

Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• efficient in Mannich reactions, as demonstrated by our studies [18] and those of others [19][20][21]. Halogen bonding has also been introduced to further broaden the field of noncovalent interactions. Despite the limited number of asymmetric transformations driven solely by halogen-bond activation [22

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

• biologically active properties. Thus, barbamide exhibits molluscicidal activity [7], and sintokamide A is active against prostate cancer [8] (Figure 1). As derivatives of strained and unique structure and properties [9][10] cyclopropanes are of interest for entering into various transformations along the path

• -3,3,3-trichloropropene (1) [40] in reactions with nucleophiles, including those following the formation of cyclic products in tandem transformations [41][42][43][44], methods for obtaining cyclopropane structures based on it are not known. In this way, it seemed desirable to synthesize vicinal

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

• , which perfomed as a key substrate for the aerobic oxidation. The formation of the tetracyclic 3-spirooxindole structure 137 was achieved through a transition-metal-free intramolecular cross-dehydrogenative coupling. With 137 in hand, a sequence of transformations including ketone reduction with NaBH4

• into the zwitterionic salt 166, extensive screening revealed that iridium catalysis with MeO-BoQPhos afforded the highest stereoselectivity. This approach furnished the reduced product 167 in high yield. After five further transformations (overall yield: 67%), the final coupling with a benzimidazole

• mechanistic hypothesis. Based on this stereochemical control, the Stoltz team successfully obtained the asymmetric hydrogenation product 176, which spontaneously underwent intramolecular cyclization to furnish the bridged cyclic compound 177. With compound 177 in hand, a series of three transformations

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• and discovery of two-electron ionic transformations dominated the early stages. Over time, pericyclic reactions exemplified by the Woodward–Hoffmann rules and one-electron radical processes became prominent research topics. Today, many of these classical transformations have been further refined to

• and accelerating the whole process. Zr-mediated catalytic radical reactions In recent years, numerous chemical transformations employing photoredox catalysts in combination with catalytic amounts of zirconium complexes have been reported. In this section, representative examples of such reactions are

• for further development in this area. In 2022, Ota and Yamaguchi et al. reported the zirconocene-catalyzed ring-opening of epoxides using Cp₂Zr(OTf)2·THF (Scheme 5) [4]. Traditionally, such transformations are carried out with low-valent titanium catalysts, which typically proceed via more substituted