Construction of CF₂ moieties in FDA-approved drugs (2016–2025): industrial routes, mechanisms, and scale-up considerations

• Wenyan Yao,
• Huanhuan Zhang,
• Xiaolong Yang and
• Feng Liu

Beilstein J. Org. Chem. 2026, 22, 1122–1150, doi:10.3762/bjoc.22.91

• -flow methods using SF4. 1.1.1 Glecaprevir and voxilaprevir (2017): As shown in Figure 2, compound 18 is the key alkyl–CF2 side chain for the synthesis of 1 and 2. There are four main methods for its construction: Route a [6] and route b [7] are based on fluorination of the terminal aldehyde group

• an inexpensive enzymatic process [8]), route a suffered from several scale-up issues: the use of OsO4 (highly toxic) and DAST (hazardous), the low fluorination yield, and a low overall yield of only 7% over ten steps. Route b [7] used compound 19, which contains an aldehyde group and a chiral carbon

• synthesis of the difluorocyclobutylamine side chain 38 in ivosidenib (3). Among them, route a (reported in 1987) [10] and route b (reported in 2005) [11] are both methods for constructing the four-membered ring. Routes c, d, and e use cyclobutane-containing starting materials and synthesize the target

Discovery of sugarnitriles A and B, and structural reassignment of SF-2140, from a sugarcane endophytic actinomycete Amycolatopsis sp. JS-O27

• Qiuyun Li,
• Ying Liu,
• Baoyue Wei,
• Yu Sun,
• Di Mao,
• Yanmin Zou and
• Shan Lu

Beilstein J. Org. Chem. 2026, 22, 1114–1121, doi:10.3762/bjoc.22.90

• (2) and B (3), were isolated from a sugarcane endophytic actinomycete Amycolatopsis sp. JS-O27. The planar structures of 1–3 were established by HRESIMS data and detailed 1D/2D NMR spectroscopic analysis, and the conformations of the sugar moieties were deduced by the analysis of 3JH-H coupling

• (2) and B (3), were isolated from a sugarcane endophytic actinomycete strain Amycolatopsis sp. JS-O27 (Figure 1). This paper describes their isolation, structure elucidation, and biological investigations. Results and Discussion HPLC analysis of the MeOH extract of rice culture of Amycolatopsis sp

• , Supporting Information File 1, and Figure 2b). The large coupling constant (J = 9.4 Hz) between H-1' and H-2' indicated both the indole and the 2'-OH to be in pseudo-equatorial positions. Furthermore, the small coupling constants between H-2' and H-3', and between H-3' and H-4'b, and NOESY correlations of H

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

• unusual carboxylated hexahydrocyclopenta[b]pyran and expands the known metabolite diversity of Rhodococcus, highlighting Rhodococcus as a source of uncommon natural-product scaffolds. Keywords: bicyclic compound; cyclopenta[b]pyran; natural products; Rhodococcus; specialized metabolites; Introduction

• than that of Streptomyces. In our continuing cultivation-based survey of metabolites from Rhodococcus, Rhodococcus sp. strain RD066637 was found to produce a new cyclopenta[b]pyran metabolite, rhodopyran (1) (Figure 1). Herein, we describe the isolation, structure elucidation, relative configuration

• , have been reported [16], whereas natural products featuring a cyclopenta[b]pyran skeleton are exceedingly rare [18][19][20][21][22][23]. Reported microbial natural products containing a cyclopenta[b]pyran motif include diospentenols A and B from Streptomyces sp. KMA-001, which possess a 7,7a-dihydro-2H

Controlled supramolecular assemblies of luminescent tridentate cyclometalated alkynylgold(III) amphiphiles in aqueous media

• Kelvin Sze-Yim Cai,
• Brian Boyan Liu and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2026, 22, 1097–1106, doi:10.3762/bjoc.22.88

• Tapping mode. The sample solution (0.2 wt %, 5.0 μL) was dropped onto a freshly cleaved mica plate surface and spin-coated to remove excess solvent. (a) UV–vis absorption spectra of GA (200 μM) in MQ water heated to 50.0 °C (red line) and cooled to 20.0 °C (black line) at a rate of 1.0 °C/min. (b

• ) Emission spectra of GA (200 μM) in MQ water upon decreasing the temperature from 50.0 °C (black line) to 10.0 °C (purple line). (a) TEM image of a thermally annealed aqueous solution of GA (2.68 mM). (b) UV–vis absorption spectra and (c) emission spectra of GA (200 μM) in Milli-Q water at 20.0 °C after

• addition of sodium tosylate (1.0, 2.0, and 4.0 equiv). (a) Time-dependent UV–vis adsorption spectra of GA (200 μM) with addition of 1.0 equiv of sodium tosylate in Milli-Q water at 20.0 °C. (b) Time-dependent absorbance changes of GA at 420 nm with and without the addition of sodium tosylate (1, 2, or 4

Synthesis and acaricidal activity against Varroa destructor of α- and γ-costic acid dimers

• Alessandro Santarsiere,
• Ernesto Santoro,
• Maria Letizia Ciavatta,
• Marianna Carbone,
• Sonia Ganassi,
• Cosimo Tedino,
• Antonio De Cristofaro,
• Antonio Evidente and
• Stefano Superchi

Beilstein J. Org. Chem. 2026, 22, 1088–1096, doi:10.3762/bjoc.22.87

• (right picture). Synthesis of costic acids derivatives. Reaction conditions: (a) ethylene glycol (0.5 equiv), pTsOH (0.1 equiv), toluene (2.0 mL/mmol), 100 °C, 4 h; (b) DMAP (0.1 equiv), DCC (1.4 equiv), CH2Cl2 (6.0 mL/mmol), ethylene glycol (1.0 equiv), 0 °C to rt, overnight; (c) DMAP (0.1 equiv), DCC

Amino acid-based surfactants: sustainable synthesis and antimicrobial mechanisms

• Rafaela Gomes Bezerra,
• Lourdes Pérez and
• Francisco Fábio Oliveira de Sousa

Beilstein J. Org. Chem. 2026, 22, 1067–1085, doi:10.3762/bjoc.22.85

• related to their antimicrobial activity; b) To describe their possible mechanisms of action in the interaction with microorganisms; and c) To present the novel approaches and perspectives on the use of these innovative molecules. Materials and Methods The methodology for this integrative review was

• Figure 3. General structure and molecular properties of amino acid-derived surfactants Several molecular structures of the cationic amino acid-based surfactants are reported in the literature (Figure 4): (a) single chain surfactants with a single amino acid on the polar head and one alkyl chain, (b

• activity against fluconazole-resistant Candida spp. (MIC: 8–12 μg/mL) by disrupting mitochondrial function and inducing apoptosis, while also exhibiting synergistic effects with amphotericin B [19]. Similarly, glycine-based solutions (4.5%) have proven effective in eradicating Streptococcus spp. and

Synthesis of functionalized, 13-alkyl-substituted coralyne derivatives and investigation of their interactions with duplex and abasic site-containing DNA

• Laurin Beckmann,
• Jason Lennard Kunze,
• Hannah Karola Strunk,
• Maurice Michel and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 1057–1066, doi:10.3762/bjoc.22.84

• )aminomethane) = 89.0 mM, c(B(OH)3) = 89.0 mM, c(Na2EDTA) = 1.0 mM, pH 8.0; I1/2 buffer: c(KH2HPO4) = 5.0 mM, c(NaCl) = 50.0 mM, pH 7.4. The ct DNA (approximately 2 mg/mL) was dissolved in BPE buffer and stored at 4 °C for at least 24 h. The solution was filtered through a membrane filter before use (pore size

• plate reader with λex = 485 nm and λfl = 535 nm was used. Structures of the representative DNA-binding protoberberine alkaloids 1a–c and coralyne (2a). Photometric (A) and fluorimetric (B) titration of ct DNA to 2e (c = 10 µM) (B) in BPE buffer (cNa+ = 16 mM, pH 7.0; with 10% v/v DMSO). Inset: plot of

• absorption (A) or emission (B) versus cDNA. CD (C) and LD (D) spectra of 2e (c = 10 µM) in the presence of ct DNA in BPE buffer (cNa+ = 16 mM, pH 7.0; with 10% v/v DMSO) at LDR = 0.0–2.0. Red: DNA in the absence of ligand, blue: LDR = 2.0. The arrows indicate the development of the bands during DNA titration

One-pot four-component sequential synthesis of S-alkyl dithiocarbamates using lipase as a biocatalyst

• Mansour Shahedi,
• Pargol Tahmasebi pour and
• Zohreh Habibi

Beilstein J. Org. Chem. 2026, 22, 1048–1056, doi:10.3762/bjoc.22.83

• . Reaction conditions: 1a–f (0.1 mmol), 2 (0.15 mmol), Novozyme 435 (30 mg), aniline (0.05 mmol), CH3CN (1 mL), 30 °C, 12 h; then, CS2 (4, 0.4 mmol), cyclic amine 5a,b (0.2 mmol), 25 °C, 12 h. Scope of the reaction with aldehydes and acyclic amines. Reaction conditions: 1a–c,e–g (0.1 mmol), 2 (0.15 mmol

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

• ) NH2OH·HCl, NaOH, EtOH–H2O (5:1), 50–55 °C, 30 min; b) NH2OH·HCl, EtOH, Et3N, 80 °C, 24 h; c) acryloyl chloride, CH2Cl2, rt; d) K2CO3, 1,4-dioxane, 120 °C, 24 h. Mechanism for the formation of novel 3,5-disubstituted 1,2,4-oxadiazolyl diarylisoxazolines 7a–ay (5-regioisomer). Precursor compounds (2a–k, 6a–j

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

• different time conditions: 1 h (reaction A), 2 h (reaction B), and 4 h (reaction C). The crude product from each reaction was pre-adsorbed to C8-bonded silica (≈1 g) and subsequently subjected to RP-HPLC using a semi-preparative C18-bonded silica Betasil column. Isocratic conditions of 10% MeOH (0.1% TFA

• dried down, and UV-active fractions were analysed by 1H NMR and UHPLC–MS, with compound 6 eluting at 34–35 min. Yields for the intended analogue 6 across the three reactions were 13% (reaction A, 1 h), 10% (reaction B, 2 h), and 6% (reaction C, 4 h), respectively. Due to the better yield of reaction A

• = 200.0 K, λ = 1.54184 Å, monoclinic, space group P21/c, a = 17.0659(2) Å, b = 7.45980(10) Å, c = 16.1534(2) Å, β = 117.493(2)°, V = 1824.22(5) Å3, Z = 4, Dc = 1.443 mg M−3, µ (Cu Kα) 1.981 mm−1, F(000) = 832, crystal size 0.33 × 0.27 × 0.06 mm3; 27980 reflections measured, θmax = 776.98°, 3842

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

• , a few examples of homoadamantane derivatives showing pronounced biological activity are known. More than 40 homoadamantane polyprenylated acylphloroglucinols have been isolated from Hypericum plants [54][55][56]. Among them, hyperacmosins A and B showed a protective effect in paracetamol-induced

• ). The NaBH4/MoO3 system [81] led to the selective reduction of only the hydroxyimino group, affording azidoamine 7. The reduction of azidoxime 4 using LiAlH4 [75][87] allowed total reduction of both the oxyimino and azido groups, resulting in the formation of isomeric diamines 8a,b (Scheme 2). Since 4,5

• -diaminohomoadamantane was isolated as a mixture of trans- and cis-isomers 8a,b, we decided to synthesize trans-4,5-diaminohomoadamantane through ring opening of aziridine 9. This compound was obtained from homoadamantanone oxime by reduction with LiAlH4 [41]. Since the aziridine ring-opening reaction usually proceeds

Z-Selective semihydrogenation of alkynes via Ni/Lewis acid synergistic catalyzed system using DMF as hydrogen source and solvent

• Lei Kang,
• Haifeng Gao and
• Luo Yang

Beilstein J. Org. Chem. 2026, 22, 1004–1012, doi:10.3762/bjoc.22.79

• hydrogenation systems. HCOOH then reacts with the Ni species to form a formate nickel hydride intermediate B (HCOONi(II)H), a key species documented in nickel-catalyzed hydrogen-transfer reactions. Subsequent selective insertion of the internal alkyne into the Ni–H bond of B affords the vinyl-nickel

• to terminal alkenes. NiCl2/Zn(AcO)2·2H2O-co-catalyzed semihydrogenation of alkylarylacetylene and dialkylacetylene to (Z)-internal alkenes. See a) Figure S2 and b) Figure S3 in Supporting Information File 1. Control experiment using DMA as solvent together with exogenous formic acid instead of DMF

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

• intermediate B, followed by coordination of diazo compound 3 to give diazonium intermediate C. The latter transforms into a carbene complex D after nitrogen loss. The next intermediate E is a result of migratory insertion of the carbenoid into the C–Rh bond. The last step of the catalytic cycle is

• performed a reaction of substrate 2a with an equimolar amount of rhodium catalyst, which allowed isolation of compound 5 (intermediate B) in 35% yield (Figure 3b). Conclusion In conclusion, we have successfully extended the strategy of Rh(III)-catalyzed chelation-assisted C–H activation/annulation with

• biologically active compounds. a,b) Structure of biologically active 2,3-dihydroimidazo[2,1-a]isoquinolines (1) and their published syntheses. c) A novel approach to annulated 2,3-dihydroimidazo[2,1-a]isoquinolines via chelation-assisted C–H activation/annulation of 2-arylimidazolines proposed in this work. d

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

• achieve the desired solvent compositions. The exact volumes used are summarized in Supporting Information File 1, Table S1. A) Bar plot representing the assembly conversion of C6-Nap-ICA 6, C3-Nap-ICA 7, and C0-Nap-ICA 8 (all 100 µM) in PBS (50 mM, pH 7.4, 1% TFE) determined through analytical HPLC. B

• -ICA 7, or C0-Nap-ICA 8 (all 100 µM) in PBS (50 mM, pH 7.4, 1% TFE) with green fluorescence filter (λex = 470/40 nm, λem = 525/50 nm), scale bar = 40 µm. A) Scheme depicting the self-assembly propensities of C6-Nap-ICA 6, C3-Nap-ICA 7, and C0-Nap-ICA 8 in aqueous media. B) TEM micrograph of C0-Nap-ICA

• room temperature. The structures were stained with uranyl(IV) acetate (4%), scale bar = 0.5 µm. Created partly in BioRender. Lahu, A. (2026) https://BioRender.com/bvkpq0n. This content is not subject to CC BY 4.0. A) Fluorescence emission and B) absorbance of C6-Nap-ICA 6, C3-Nap-ICA 7, and C0-Nap-ICA

Electrochemical reduction of unsaturated carbon–carbon bonds via 3d transition-metal catalysis

• Geon Kang,
• Minki Jeon,
• Pooja Kumari Jat,
• Cheoljae Kim and
• Isaac Choi

Beilstein J. Org. Chem. 2026, 22, 955–981, doi:10.3762/bjoc.22.75

• the use of stoichiometric reagents. In this context, when electrochemistry is employed as a synthetic tool in organic chemistry, several critical parameters must be taken into account, including (a) electrode, (b) electrolysis mode, and (c) cell configuration (Figure 1). Among these, the choice of

Synthesis of sterically shielded piperidine nitroxides via acid-catalyzed heterocyclization of β-aminoketone derivatives with ketones

• Mark M. Gulman,
• Yurii I. Glazachev and
• Sergey A. Dobrynin

Beilstein J. Org. Chem. 2026, 22, 948–954, doi:10.3762/bjoc.22.74

• -tetrapropyl-substituted piperidine nitroxides, and sterically shielded nitroxides with functional groups in the side chain of the heterocycle. Results and Discussion Aminodioxolanes 4a,b were obtained from enones 1a,b via a modified literature sequence [30] involving phthalimide Michael addition, dioxolane

• formation, and hydrazinolysis (Scheme 1). The target 2-(2-aminoalkyl)-1,3-dioxolanes 4a,b were obtained in pure form after vacuum distillation. Conversion of α,β-unsaturated ketones 1a,b to aminodioxolanes 4a,b proceeded in 49% and 69% overall yield, respectively. In the 1H NMR spectrum of 4a

• ), the N-adjacent methine (2.71 ppm), and diastereotopic methylene protons (1.39, 1.58 ppm) supported the assigned structure. Compound 4b exhibited spectral data identical to those previously described [31]. The aminodioxolanes 4a,b were subjected to acid-catalyzed heterocyclization with the

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

• activated olefin, followed by aminocupration across the C=C bond to form the alkylcopper intermediate IV, which subsequently underwent proton transfer with aniline to furnish the β-amino product 1 while regenerating the copper–amido species II. Alternatively, path B proceeded through the direct nucleophilic

• or free ligands alone were ineffective, indicating that discrete copper–amido complexes served as catalytically active species, rather than merely functioning as Lewis acids. Although both pathways are mechanistically plausible, experimental evidence supports the nucleophilic addition pathway (path B

• that this key step could occur through either four- or six-membered cyclic transition states (III-a vs III-b), depending on the nature of the electron-withdrawing group on the olefin. Finally, proton transfer from the amine substrate released the hydroamination product and regenerated the active Cu

A practical CO₂-mediated synthesis of 5,6-carboxylated silicon-rhodamines for targeted probe development

• Dongjie Hou,
• Shaowei Wu,
• Ning Xu,
• Pengjun Bao,
• Wenhao Jia,
• Qinglong Qiao and
• Zhaochao Xu

Beilstein J. Org. Chem. 2026, 22, 915–924, doi:10.3762/bjoc.22.72

• -resolution imaging. Overall, this work improves the synthetic accessibility of functionalized SiR dyes and provides a concise and versatile platform for the rapid development of targeted super-resolution probes. (a) Modular structure of spirocyclic rhodamines. (b) Conventional carboxylation strategies. (c

• ) CO2-based direct carboxylation method developed in this work. (a) Direct carboxylation of brominated silicon-rhodamines 1a–c under n-BuLi/CO2. (b) Strategy for the one-pot functionalization of brominated silicon-rhodamines 1a–c to construct SiR–halo fluorescent probes 4a–c. (a–c) Conversion of three

• fusion protein, and mitochondria labeled with TOMM20-HaloTag fusion protein. (b) Average localization precisions of 4a and 4b for different organelles. (c) Long-term SMLM imaging of actin with 4b in live HeLa cells. (d) Schematic diagram of filopodia growth and wiggling process in (c). Scale bars: 5.0 μm

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

• efficient access to chemodivergent products. The developed reaction protocol is expected to be applicable to the synthesis of functional materials and bioactive molecules. Nuclear Overhauser effect (NOE) correlations in products (a) 3ab, (b) 3ac, (c) 3ad, (d) 3aj, and (e) 3ak. Various transition-metal

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

• ) exhibiting a lower relative Gibbs free energy than the starting compounds. According to the calculations, the reaction of azirine 1a and benzaldehyde 2c results in the formation of two diastereomers, (RR,SR)- and (RR,RR)-A, which can undergo a conformational transition to intermediates (RR,SR)- and (RR,RR)-B

• , which are capable of cyclization. The cyclization of (RR,SR)-B leads to the (1RR,3SR,6RR)-Pha-C isomer with the Ph group from benzaldehyde in the axial position, which readily transforms into the more stable (1RR,3SR,6RR)-Phe-C isomer with equatorial Ph group as a result of inversion of the 6-membered

• ring. The intermediate (RR,RR)-B immediately yields a more stable conformer with the Ph group from benzaldehyde in the equatorial position (1RR,3RR,6RR)-Phe-C, but the equilibrium as a whole is shifted towards the most stable isomer (1RR,3SR,6RR)-Phe-C isomer. According to the calculation, the

Chiral cyclopropenimine-catalyzed enantioselective Michael reactions of phenol and benzofuran-derived α,β-unsaturated pyrazolamides with benzophenone-imine of glycine esters

• Ya Bai,
• Xue-Ying Wang,
• Si-Kai Zhu,
• Yan-Ting Shen,
• Sheng-Yong Zhang and
• Ping-An Wang

Beilstein J. Org. Chem. 2026, 22, 888–896, doi:10.3762/bjoc.22.69

• anti-form of 6a. With mode B, the π–π stacking between benzophenone-imine 2a and the phenoxylmethyl group in 5a may enhance the ratio of this attack to produce the syn-form of 6a as major product. A mechanism for this highly enantioselective Michael addition between 2a and 5a was proposed based on

• ion pair A, which attacks β-substituted α,β-unsaturated pyrazolamide 5a to provide transition state B. Transition state B may be stabilized through an H-bonding interaction network between the two substrates and CSB-1. Additionally, π–π stacking between the two phenyl groups of 2a and 5a may also

• enhance the formation of transition state B. The highly diastereomic ratio of 6a in syn-form may be generated from transition state B. The formation of intermediate C is the rate-limiting step. When intermediate C is formed, the protonation happened rapidly to afford 6a in high enantioselectivity. The

Diastereodivergent electrophilic trapping of α-boryl lithium derivatives

• Tereza Pavlíčková,
• Noam Orbach and
• Ilan Marek

Beilstein J. Org. Chem. 2026, 22, 882–887, doi:10.3762/bjoc.22.68

• delocalization leads to the formation of a partial π C–B bond (Scheme 1) [1][2], which provides a unique stabilization to the carbanionic center and affects its reactivity towards electrophiles. In recent years, α-boryl carbanions have attracted significant attention as highly versatile intermediates capable of

• calculations, this model assumes initial coordination of both the vinyl group and the Bpin moiety to the lithium counterion. Within this constrained geometry, when R2 = H, R3 = alkyl, the diastereocontrol is then governed by the relative steric interactions present in these two possible conformers B and C

• . This conformational constraint rigidifies the system through formation of a pseudo-ring, leading to potential gauche interactions between R1 and R3 in conformer B (Scheme 5). In conformer C, however, substituents R1 and R3 are further apart, which expose a free diastereotopic face above the plane of

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

• , with applications in ADC development, radiolabelling and ROS/Ca2+ imaging (Scheme 9a) [86][87][88][89][90][91]. Methionine can also be modified via sulfonium conjugates using hypervalent iodine (23, Scheme 9b) [92] or photoredox approaches (24a/b, Scheme 9c) [93]. Histidine has been targeted using

• key amines on insulin, including the N-terminal glycine of chain A, the N-terminal phenylalanine of chain B and the ε-amino group of lysine B29. Using a colony picker and UPLC analysis, mutations were introduced within the binding pocket (to enhance localised recognition of insulin) and at distal

• (1), b) reductive amination by sodium cyanoborohydride, c) native chemical ligation, d) cysteine-reactive 2-cyanobenzothiazole 2 and e) formylphenylboronic acid 3 (FPBA) reacting with N-terminal cysteine. Introduction of carbonyl functionality at protein N-termini via a) oxidation by periodate, b

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

• of Pt–CO. Bonding analysis of these CO complexes indicates mainly σ-donation but little back-donation, with donation/back-donation (d/b) ratios much larger than in the comparable Pt(II) complex [(C^N^N)Pt–CO]+. DFT studies found no evidence for π-bonding contributions to the Au–CO bond in the highest

• be underestimated. For example, cleavage of one of the Au–phenyl bonds in A (Scheme 2) with a strong acid provides access to the gold borane and silane σ-complexes [(C^N–CH)Au(C6F5)(H–X)]+, X = B(O2C2Me4) or SiEt3 (Scheme 3) [32]. In the presence of traces of moisture, the Au(III)+ Lewis acidity may

• the range of dianionic C^C chelates to dicarboranyls highlights the effects of electronic characteristics. For example, while the removal of a trifluoroacetate ligand by B(C6F5)3 can usually be relied upon to quantitatively create a vacant coordination site [27][28][29], in the case of 7 this method

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

• ), the second redox stage splits into two steps. The first yields a relatively stable cation radical (Ic/Ia = 0.45–0.50) (Scheme 2, path b), while the subsequent redox transition occurs at higher potentials (2.03–2.06 V) (Figure 3). In the case of catechols 7 and 7a, the second oxidation peak appears in

• antioxidants, stimuli-responsive materials, and functional ligands for metal complexes with tailored electronic properties. Molecular structures of 1a (a), 4a (b), 5a (c), 6a (d), 7a (e) (solvent molecules and fragment disordering are omitted; for 4a and 5a, only one independent molecule is shown). CV curves

• ). Synthesis of catechol-contained thioethers 1–7 and sulfoxides 1a–7a. Proposed mechanism of electrochemical transformations of catechol sulfoxides (path a – for 1a, 3a, 4a, 6a, and 7a; path b – for 2a and 5a). Proposed mechanism of the reduction of electrogenerated o-benzoquinone. Peak (Epox) potentials of 1