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

• complex. A) Lewis structure of the truncated tweezer peptide monophosphate 2b. B) Close-up of the binding motif formed by 2b (tweezer: green, butynyl ester: red) on the survivin surface encapsulating Lys-121 after MD simulation (Desmond, 100 ns, 300 K, 0.15 mM NaCl) using explicit water solvent. A

Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• epoxide 9b, the more positively charged epoxide carbon is sterically shielded by the neighbouring ester carbonyl group. As a result, nucleophilic attack occurs at the sterically more accessible, albeit less positively charged, epoxide carbon. These observations indicate that the regioselectivity of

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

• metathesis with ethyl acrylate, acidic cleavage of the diol protecting group and addition of NaH induced the oxy-Michael reaction towards 18 in 4:1 dr. Reduction of the ester moiety, subsequent protection with TBDPSCl and methylation of the secondary alcohol furnished 19. After Bn-deprotection, iodination

• aldehyde motif (equilibrium of lactol to aldehyde and alcohol) was trapped by HWE reaction to obtain 95. The secondary alcohol unit of 95 was protected and the ester reduced to the respective alcohol, before Sharpless epoxidation, oxidation of the alcohol and subsequent Wittig reaction yielded allylic

• )/Cr(II)-mediated coupling of 1-bromo-2-trimethylsilylethene, acidic cleavage of the remaining cyclohexylidene ring, TBDMS-protection of the three alcohol units and electrophilic substitution of the silyl moiety to afford vinyl iodide 103 was applied. Eventually, ester 103 was reduced to target

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

• extractants. Here, we report the design and synthesis of PCP HA, a phenoxycalix[4]pyrrole scaffold functionalized with four hydroxamic acid (HA) groups, and evaluate its uranium(VI) extraction potential. PCP HA was synthesized from its ester precursor (PCP E) via hydroxyaminolysis using KOH, achieving a 95

• aldehydes [45], alcohols [46], and amides [47] have also been reported. However, the literature states that there is no particular reagent or reaction condition that can serve as a general rule for the synthesis of hydroxamic acids [48]. In this study, the direct reaction of hydroxylamine with the PCP ester

• was first examined, since the ester functions as the synthetic precursor to the corresponding acid used in the preparation of PCP derivatives from PCP [21]. For that, PCP was initially synthesized through the molecular cyclisation of pyrrole with 4-hydroxyacetophenone in methanol in the presence of

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• to its corresponding NHS ester 8 and residual starting material was removed by column chromatography. The Boc-protecting group was removed under anhydrous conditions in good yield and the structure of 9 was confirmed by NMR spectroscopy. Compound 9 was maintained as the TFA salt for the final step

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

• possible to use an ester group for the cleavage of 3-sulfonylpyrrolidines, it required a longer reaction time and provided a slightly lower overall product yield (77%) compared to the use of the benzoyl group. With an optimized synthetic route in hand – comprising a multicomponent reaction of ketosulfone

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

• of CeO2 to attack the carbonyl carbon, leading to cleavage of the C–N bond (B). Subsequent nucleophilic attack of the octoxide anion on the activated carbonyl center (C) then furnishes the ester product. Later, the same group found that niobium could also serve as a heterogeneous Lewis acid catalyst

• undergoes hydrolysis to afford the benzyl ester 30. Under the optimized conditions, primary, secondary, and tertiary amides 12, 31–33 were successfully converted to benzyl esters in high yields. Notably, loss of enantiopurity of chiral amide 33 was not observed during esterification. Sulfuryl fluoride

• 1), addition of water affords adduct M, which subsequently converts to the ester via deprotonation. In dry solvents (path 2), nucleophilic attack by the departing OSO₂F− anion on L produces intermediate N, containing an S–O bond that is ultimately cleaved under basic conditions to yield the ester

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

• ) starting from (−)-carene (155), already containing the dimethyl cyclopropane motif [243][244]. Intermediate 156 was reached after 29 linear steps and suggested to be the crucial biosynthetic precursor (protected as its acetate, see Scheme 37A). Treatment with strong alkali cleaved the ester in 156

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

• animals [31][32][33]. However, some representatives of these compounds (Scheme 2) find applications in pharmacology [34] due to their antimicrobial (megalanthonine; subulacine N-oxide) [35][36], anti-inflammatory (lindelofidine, benzoic acid ester; paludosine) [37][38], anticancer (ligulachyroine) [39

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

• cyclohexene derivatives beyond sulfone and sulfonamide motifs. By combining ester enolate and amine addition sequences, this methodology was subsequently extended to the synthesis of architecturally complex polyheterocyclic frameworks (Scheme 3B) [62]. Such scaffolds are scarcely represented in contemporary

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

• (Scheme 3) involved the optimization of a two-step procedure reported previously for their preparation from corresponding anilines and malonic ester [40][41][42][43]. The intermediate N1,N3-bis(4-halogenophenyl)malonamides 1a–c were synthesized from 4-halogen-substituted anilines and diethyl malonate in

• nucleophilic attack by the alcohol on the carbonyl group of the Meldrum’s acid fragment, thereby favoring formation of an open-chain ester rather than a lactone upon decarboxylation. Following this rationale, the reaction of 4-hydroxyquinolin-2-ones 2a–c, 3,4-dimethoxybenzaldehyde, and Meldrum’s acid in

• reaction conditions, the lactone forms predominantly (Scheme 1B). However, the lactone appears capable of slow transesterification in the presence of excess alcohol, converting it into the open-chain ester upon prolonged heating. The lower stability of the cyclic product, compared to the open-chain ester

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

• rely on phosphate rock but instead uses biomass as a phosphorus source. Keywords: diaryl phosphates; phosphate esters; phosphate ester synthesis; phosphorus recovery; phytic acid; Introduction Phytic acid (myo-inositol-1,2,3,4,5,6-hexakisphosphate, Scheme 1) is a phosphorus-rich molecule, which is

• phosphates [16]. Drugs and reagents containing phosphate ester moieties were designed as analogs of these molecules [16][17][18][19][20]. Phosphate monoesters with long aliphatic chains have also been used as surfactants [21]. Phosphate triesters are utilized as flame retardants and plasticizers for polymers

• esterification with alcohols using sustainable biomass-derived phytic acid as a phosphorus source (Figure 2E). This approach can facilitate the development of environmentally friendly phosphate ester production as well as phosphorus recovery and recycling techniques. To date, the preparation of phosphate esters

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

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

• conditions, the selective S–O bond formation has been largely overlooked, rendering the direct synthesis of sulfinimidate esters from alcohols a nontrivial and underdeveloped transformation. Results and Discussion To validate our hypothesis and identify optimal conditions for sulfilimidate ester formation

• bearing an iodoalkyl side chain provided the product 3w’ in 39% yield. Also a hydroxy-functionalized alcohol, derived from prop-1,3-diol, afforded the corresponding sulfinimidate ester 3x’ in 35% yield under the standard conditions (conditions d), where 2.5 equivalents of the alcohol, NBS and NaHCO3 were

• with improved chemoselectivity toward monosubstitution and the yield of product 3x’ increased to 64%. Notably, although ester 3x’ contains two hydroxy groups, no bis-substituted product could be detected under either set of conditions. To demonstrate the practicality and synthetic utility of this

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

• stirred at room temperature until a suspension was formed (ca 5 min). After that, the reaction mixture was cooled to −20 °C. The malonic ester (0.171 mmol, 3.0 equiv) was added to the reaction vessel via syringe. The reaction was stirred at −20 °C for an appropriate time. The progress of the reaction was

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

• % yield over two steps [76]. Alkylation with MeI furnished pyridinium 91, which was hydrogenated in two steps with NaBH3CN to the fully saturated piperidine 92. Acidic removal of the benzoyl group triggered auto-oxidation to the indole, and subsequent hydrolysis of methyl ester delivered the target

• , Johnson–Claisen rearrangement, enol ester formation, and methylation afforded 140. Finally, hydrogenation of 140 via PtO2/H2 generated the target molecule (±)-corynoxine, and under acidic conditions, (±)-corynoxine could be isomerized to (±)-corynoxine B (Scheme 19). Total synthesis of (+)-serratezomine E

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• reactions mainly involve the initial electrophilic attack onto the α-position relative to the hydrogen atom. The selectivity is either due to the high stability of the α-nucleophilic conformer or due to the promotion by the adjacent ester group. Cascade reactions upon the target connection, if installed

• planarity of the two neighboring ester groups and thereby stabilize the anion. The prevalence of this isomer is also confirmed by the NMR data [21], however, other conformers with different charge distributions are also available in solution. To understand the nucleophilic reactivity of the most stable

• 11. The 1,5-arylazo shift has been previously investigated in cyclopentadiene systems [32]. Subsequent formation of norcaradienes 12 and azocyclopropane rearrangement [33][34][35] afford a mixture of isomeric dihydroindazole derivatives 8 and 9 which differ in positioning of one ester group. The

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

• also be applied to hydroxy- or carboxylic acid-containing olefins by adding 1.1 equivalents of HB(pin) to perform traceless protection of these functional groups, which are otherwise incompatible with molybdenum metathesis catalysts. The in situ-generated boronic ester is conveniently cleaved by silica

One-pot synthesis of ethylmaltol from maltol

• Immanuel Plangger,
• Marcel Jenny,
• Gregor Plangger and
• Thomas Magauer

Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212

• commenced our investigation with acetylation of maltol (2) using acetic anhydride to afford ester 8a. Unfortunately, the acetate group proved labile upon treatment of 8a with lithium bis(trimethylsilyl)amide (LiHMDS), resulting exclusively in deprotection to give maltol (2, Table 2, entry 1). Turning to the

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

• -nitro-2-nitrosopropanoates (1g and 1h), which contain an additional electron-withdrawing ester group in geminal position. Finally, 1-nitrosocyclohexane-1-carbonitrile (1i) was also tolerated under the reaction conditions, affording product 2i in 61% yield. The robustness of the developed protocol was

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• bond formation and functional group compatibility presented unforeseen challenges. Methods for the chemical synthesis of prenyltryptophans (approach A, A–C) are scarce [25][26]. Adopting a bio-inspired approach, Ishikawa et al. treated tryptophan ethyl ester with prenyl alcohol in the presence of 2

• amorphous powder. Viswanathan [25] and Chen [28] reported a C-2 prenylation of tryptophan methyl ester mediated by acid salts and Lewis acids, respectively. A prenylation at C-4 in bis-N-Boc-tryptophan methyl ester has been achieved by Chein utilizing optimized Suzuki coupling conditions [29]. Results and

• alternative approach to C-7 functionalization of Nα-Boc-tryptophan methyl ester, we chose a CH activation protocol [33]. Treatment of N1-Piv-Nα-Boc-tryptophan methyl ester (10) with but-3-en-2-one (MVK) in the presence of [RhCp*Cl2]2 catalyst according to Ma et al. [34] led to the 7-(3-keto-1-butyl)-alkylated

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

• are cyclized with aldehydes and ammonia (monoamines) or urea to yield a certain type of products only: pyridines and pyrimidines; and formation of the products proceeds with the involvement of an acyl fragment and the meso-position of an oxo ester component [9]. Although the introduction of 2

• for 3-polyfluoroalkyl-3-oxo esters containing an activated carbonyl group capable of adding α-methylene ketones. It is characterized by the cyclization at the 1,3-dicarbonyl fragment of 3-oxo ester and offers a possibility of using a variety of nucleophilic agents to form hydrogenated diastereomeric

• a microwave (MW) reactor (Table 1, entry 6). It turned out that after 24 hours of heating the complete conversion of oxo ester 1 occurred and the overall yield increased to 83% (Table 1, entry 5), whereas the use of MW reduced the reaction time down to five hours (Table 1, entry 6), but the contents

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• -methylene group and an ester reduction/Appel reaction sequence to convert the ester moiety to an iodide leaving group. The right-hand fragment (E/F-ring) was synthesized from tert-butylsiloxyfuran 39. Commencing via an asymmetric allylic alkylation and an aza-Michael reaction, butanolide 40 was obtained in

• (12), only one synthesis is reported [14]. The Masamune group disclosed this synthesis in 1968, starting with a sequential ring construction of the C, B and A-ring from Hagemann’s ester (61) to C-nor-D-homo steroid precursor 62 (Scheme 13). The piperidine F-ring was then coupled after D-ring

• oxidation and the double bond installation mentioned, including several redox manipulations and protecting group removals. In total, the Masamune group reported the total synthesis of jervine (12) from Hagemann’s ester (61) in 47 steps in the LLS and a total of 49 steps. Not all yields were reported, so no

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• ): reduction of 8 with NaBH4, followed by chlorination of alcohol 36 with SOCl2 and substitution of chloro derivative 37 with various amines resulted in compounds 38a–c. Tianeptine analogue 38d was obtained by hydrolysis of ester 38c. The synthesis of the new regioisomeric tetracyclic compounds containing the

• regioselectivity. Reduction of 51 with NaBH4 and subsequent chlorination of alcohol 52 with SOCl2 gave chloro derivative 53, which was treated with amines to afford compounds 54a–e. 7-Aminoheptanoic acid ester derivative 54e was hydrolyzed to tianeptine analogue 54f. Conclusion As continuation of our efforts to

• (1 Cl); HRESIMS (m/z): [M + H]+ calcd for C25H32ClN2O6S, 523.1664; found, 523.1668. 7-[(9-Chloro-6-methyl-7,7-dioxido-2,3,6,12-tetrahydro[1,4]benzodioxino[6,7-c]benzo[f][1,2]thiazepin-12-yl)amino]heptanoic acid (21b): To a solution of ester 21a (2.615 g, 5 mmol) in EtOH (30 mL), NaOH (0.240 g, 6 mmol

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

• , 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

• presence of NHC (10 mol %) and 4CzIPN (2 mol %) and Na2HPO4 in DMSO at rt for 10–24 h. The key to success lies in the photocatalytic dual system, which combines two organocatalysts (NHC/4CzIPN) and visible light irradiation to permit a novel umpolung single-electron reduction of respective imino ester 2

• arylcyclopropanes 5 by applying NHC/ photoredox cooperative organocatalysis under visible-light irradiation. This method allows sequential C–O and C–C bond formation, leading to access to various γ-aroyloxy keto-ester derivatives 6 in good yield up to 81% and excellent functional group tolerance, including electron