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

• acid or its ester (Scheme 1). In both cases, condensation of amino acids with carbonyl compounds occurs; however, in the first case, decarboxylation occurs with the in situ formation of azomethine ylides, which subsequently undergo cycloaddition to unsaturated substrates. The advantage of the first

• diastereoselectivity (>20:1) and enantioselectivity (89–96% ee) regardless of the electronic and steric properties of the aromatic ring in the α-(arylimino)ester (Scheme 4). However, when using other dipolarophiles, such as dimethyl maleate, tert-butyl crotonate, and tert-butyl cinnamate, a noticeable decrease in

• iminoester 1 with tert-butyl acrylic acid ester 4 occurs first. This is followed by condensation of pyrrolidine 9 with cinnamic aldehyde (10) to form azomethine ylide B, which enters into a second diastereoselective 1,3-DC with various electrophilic alkenes. The authors used acrylic acid esters, vinylphenyl

Anti-invasive and cytotoxic evaluation of a (+)-pinoresinol-based semisynthetic library against glioblastoma

• Chen Zhang,
• Kah Yean Lum,
• Jonathan M. White,
• Paul I. Forster,
• Nicholas Booth,
• Sunita A. Ramesh and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 691–704, doi:10.3762/bjoc.22.54

• two new pinoresinol ester derivatives 6 and 7 showed the biggest differences to the natural products owing to the addition of UV-active acyl moieties. Owing to our developing interest in identifying natural products and derivatives that are cytotoxic to human cancer cell lines and/or block invasion or

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

• allylic position C13 being oxidized, a second allylic oxidation would possibly occur at the desired C5 position. However, when compound 8, as well as its acetyl ester (Ac) and tert-butyldimethylsilyl ether (TBS) derivatives, were subjected to several metal-mediated allylic oxidation conditions, either no

• the benzoate ester for reductive deoxygenation were not successful [63], and 13a/b decomposed in the esterification step. We have finally found that the 13-hydroxy group could be smoothly removed by the methyl oxalyl ester deoxygenation method [64][65]. Thus, 13a/b were esterified with methyl

• bond of 15 was confirmed to be Z based on the NOESY correlations between 13-H/20-H3. The formation of product 15 could be attributed to the isomerization of the C13 allylic radical, generated by methyl oxalyl ester deoxygenation step, to the C11 allylic radical, followed by hydrogen abstraction from n

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

• native framework while serving as a more accessible synthetic handle for downstream coupling chemistry. As 1 itself was known not to have any effect on cell viability while its uncharged methyl ester analogue did, the neutralised pro-drug analogue of the ATP-site binder was employed to prevent such

• PROTAC precursors 17–20 in moderate to good yields (35–49%; Scheme 1). Before progressing to full PROTACs, it was essential to confirm that the modified CAM4066 scaffold tolerated linker installation. For this, the methyl ester of the key ligand–linker precursor 17 was hydrolysed using aqueous LiOH to

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

• the ester moiety, and the product was isolated by simple evaporation of the solvent from the collected fraction eluted from the flow reactor (Table 2, entry 6). Cyclic ketones 1g, 1h, and 1i and an aliphatic ketone 1j were also hydrogenated in excellent yields at room temperature (Table 2, entries 7

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