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

• hydroxy group allowed the synthesis of compound 1 from 4 in nine steps. Selective acid-mediated 5,10-transannular cyclization of 5 followed by hydration reaction furnished both products 2 and 3 in two steps. Keywords: chemoenzymatic synthesis; chiral pool; isopentenol utilization pathway; terpene

• compounds 1, 2, and 3 is depicted in Scheme 1 [40][41][42]. We envisioned that by selective oxidation at C5, compound 1 could be directly obtained from casbene (4). The macrocyclic casbane-type skeleton could be produced by an engineered heterologous host harboring both casbene synthase (CS) and an

• 3, respectively, in a more efficient and selective way by protein engineering, we thought that germacrene A (5), whose terpene cyclases are widely found in different organisms [52], could serve as a precursor for synthesis of both 2 and 3 via a transannular cyclization process [37][53][54]. A

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

• extensively in this review. For instance, selective degraders of CDK isoforms are advancing through early-phase trials [33], with molecules like BSJ-03-123 and others showing promise in hematologic malignancies by exploiting the subtle structural differences among the highly homologous CDK family members to

• ability to target the degradation of CDK6, and proteomics results also show that compound 2 has no degradation effect on CDK4. In 2020, Benowitz and co-workers carried out a project to explore the impact of different E3 ligands on the selective degradation of CDK4/6 [57]. In their research, they designed

• PROTACs for the selective degradation of CDK6 [60]. They also constructed a PROTAC-CP 10 (6) containing a triazole-containing linker to connect palbociclib and pomalidomide. Compound 6, a selective CDK6 degrader, showed good selectivity in U251 cells (DC50(CDK6) = 2.1 nM; DC50(CDK4) > 100 nM) and the

Hydrogen production from formic acid catalyzed by NHC–Cu complexes

• Orlando Santoro and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2026, 22, 620–627, doi:10.3762/bjoc.22.48

• ][29] and Rh [30][31] have shown to allow the selective transformation of formic acid into H2 and CO2 with high turnover frequencies (TOFs). In most cases, addition of a base (either amines or formate salts) is required to obtain high catalytic activity. Efficient systems based on inexpensive metals

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

• adjacent to the ATP-binding site of CK2α [5][6]. Fragment-based ligand discovery subsequently enabled the development of CAM4066, a selective inhibitor that simultaneously engages the αD and ATP sites. CAM4066 validated the αD region as a tractable and selective binding pocket for CK2 kinase inhibition

• potent and selective PROTAC targeting CK2 might be valuable in the evaluation of specific degradation of CK2 as a therapeutic approach. Herein, we report the design and synthesis of a series of CK2-targeting PROTACs. CAM4066 was selected as the warhead to enable CK2-specific target engagement. We

• geometry, and E3 ligase selection. Conclusion In summary, we have developed a modular synthetic platform for the construction of CK2-targeting degraders 23–26, 28, and 29 based on the selective bivalent inhibitor CAM4066. Structure-guided design enabled identification of a solvent-accessible exit vector

Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity

• Artem S. Sazonov,
• Dmitry A. Vasilenko,
• Denis V. Porfiriev,
• Yuri K. Grishin,
• Rimma A. Gazzaeva,
• Alisa P. Chernyshova,
• Maxim A. Kryakvin,
• Anna A. Baranova,
• Vera A. Alferova and
• Elena B. Averina

Beilstein J. Org. Chem. 2026, 22, 592–602, doi:10.3762/bjoc.22.45

• nucleophilic aromatic substitution with thiophenols followed by oxidation with m-chloroperbenzoic acid (mCPBA). The scope of the reactions was explored, demonstrating high yields across a variety of functional groups and substituents. Optimized conditions enabled selective oxidation of thioaryl groups to

Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• -selective degrader, and for the first time confirmed its ability to degrade the membrane-bound form of FGFR2. This work provides an innovative targeted protein degradation strategy for the treatment of FGFR2-driven tumors and holds significant potential for clinical application. Keywords: CRBN; erdafitinib

• ; FGFR2; selective degrader; Introduction Fibroblast growth factor receptors (FGFR) are a family of single-pass transmembrane receptor tyrosine kinases (RTKs) localized on the cell surface that bind to fibroblast growth factors [1][2][3]. Dimerization and autophosphorylation of FGFRs are induced by their

• cholangiocarcinoma [16][17][18]. Accordingly, research into therapeutics targeting FGFR2 has emerged as a major focus. To treat FGFR2-driven tumors, current research primarily focuses on two distinct classes of inhibitors, namely FGFR pan-inhibitors and FGFR2-selective inhibitors. Among these in Figure 1

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

• often suffers from insufficient reactivity and conversion, even under harsh reaction conditions, such as high temperature and pressurized hydrogen, or when employing advanced technologies [8][9][11][12]. The selective hydrogenation of carbonyl moieties often needs to overcome the problem of

• overreduction of other functionalities like aromatic systems, and requires additives to suppress this unwanted side-reaction [6][10]. We have developed heterogeneous bimetallic nanoparticle catalysts for the selective hydrogenation of quinizarin to leucoquinizarin under continuous-flow conditions [30]. During

• our mechanistic study, we unexpectedly discovered that Pt–Fe bimetallic nanoparticles immobilized on a composite support of dimethylpolysilane (DMPSi) and alumina (Pt‒Fe/DMPSi–Al2O3) exhibited extraordinary catalytic performance for the selective hydrogenation of ketones under continuous-flow and

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

• attached phosph(on)ate anions as powerful new hosts for the amino acids lysine and arginine. In the recent past, we demonstrated that the affinity and selectivity of our lysine-selective molecular tweezers could be improved by attaching natural peptide recognition elements. This could be documented in

• various projects with tailored peptide tweezer conjugates: For example, the self-complementary ELTLGEFL sequence of the nuclear export signal in survivin was coupled to tweezers which rendered them selective for this important interface (NMR evidence, 1:1 stoichiometry, K/A mutants) and prevented the

• selective for accessible lysine residues was covalently connected to the histone H3 peptide at various distances to add the released lysine inclusion energy (Kd ≈ 10 µM) and reach nanomolar affinity. Azidopeptides were conjugated to butynyl tweezers by click chemistry and subjected to competitive

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

• , Nicolaou and co-workers merged both building blocks within a Ni(II)/Cr(II)-catalyzed NHK reaction using chiral ligand 206 (Scheme 23) [95]. Upon treatment with DBU, 3-methylenetetrahydrofuran 201 was obtained in 56% yield over two steps. PMB-deprotection, iodination and selective reduction of the ester

• allylation, 280 was isolated as a single diastereomer upon recrystallization. The dihydroxylation, oxidative cleavage and reduction with NaBH4 afforded diol 281, whose primary alcohol unit was protected enabling the selective oxidation towards ketone 283. Olefination with 293 (Nysted reagent) and

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

• selective remediation strategies. Supramolecular materials, with their pre-organized structures, offer a promising route for uranium removal. Phenoxycalix[4]pyrroles (PCP) are well-known supramolecular scaffolds capable of selective metal binding, making them attractive candidates for designing uranium

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

• biaxial terphenyl atropisomers with chlorinated and brominated variants to achieve high diastereo- and enantioselectivity. The process takes place via a two-step kinetic resolution. In 2021, Shi and co-workers reported a highly trans-selective synthesis of axially chiral styrenes 76 containing a

• hydrocarbons. Catalytic synthesis of biaxial triphenylene block-transfer isomers. A Pd(II)-catalyzed trans-selective C–H alkenylation strategy through thioether-directed olefination. Synthesis of N-arylphthalimides from prochiral maleimides and NHC-activated dienolides. Ni-catalyzed synthesis of triaxially

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• reaction with 2-naphthol as the dinucleophile is also known [32]. In all cases, the regiochemistry of cyclization is selective and no isomeric products are formed. Conclusion In this report, we confirm the finding by Martinez [28] and Kozlov [29][30] that the three-component reaction originally claimed to

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• -substituted oxacyclophene 1ad We planned to construct the nine-membered cyclic ether skeleton of 1ad in the final step by an intramolecular Williamson etherification of haloalcohol 2 (Scheme 1). The iodine-substituted Z-alkene moiety of 2 was planned to be introduced through a trans-selective hydroiodination

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

• strategy similar to that described above for the preparation of calixarenes 24–26 involving nitration of calix[4]arenes followed by selective reduction of the nitro groups could not be implemented for the preparation of p-aminocalix[4]arenes bearing 2-azidoethyl groups at their narrow rims. To overcome

• hampering or preventing a catalytic hydrogenation of these compounds. On the other hand, in calixarenes 31 and 32, which are immediate products of the selective reduction of the nitro groups in compounds 29 and 30 under neutral or basic conditions, the free amino groups may be alkylated by a neighboring

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• , 7, and 9 were selective against the tested lines. Compound 9 can be classified as the most attractive and promising candidate for further development against cervical adenocarcinoma. Keywords: ADMET analysis; anticancer activity; 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines; Introduction Purine

• activity. They combine purine-like recognition features with the synthetic flexibility of heterocycles, offering a platform for selective targeting of tumor-related enzymes and receptors. Tumor cells overexpress kinases, DNA/RNA polymerases, and metabolic enzymes that bind purine nucleotides. Cancer cell

• oxazolopyrimidine derivatives may demonstrate selective cytotoxicity against cancer cell lines like HeLa, HepG2, A549, and central nervous system (CNS) tumor models [1][2][3]. The introduction of heterocyclic molecules with different amino groups as hydrogen-bond donors (and sometimes acceptors via lone electron

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

• enables selective oxidative hetero-coupling followed by dehydrative cyclization, furnishing the extended [8]helical scaffold efficiently under mild, oxidant-free conditions. Structural analyses show retained aromaticity, increased helical distortion, and higher configurational stability (≈38 kcal/mol

• designed coupling partners to control both chemo- and regioselectivity. A finely tuned anodic sequence enables selective oxidative hetero-coupling followed by dehydrative cyclization, delivering extended [8]helical scaffolds efficiently under mild, oxidant-free conditions. Combined experimental and DFT

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

• , bioactive molecules, and advanced materials. However, its exceptional resonance stabilization renders the C–N bond highly inert, posing a persistent synthetic challenge for its transformation. While twisted amides with distorted C–N bonds have offered useful reactivity enhancements, the selective activation

• catalysis, electrophilic activation, strong base-counter-cation systems, and N-based activating groups that enable chemoselective bond cleavage. Together, these developments provide powerful tools for amide functionalization and offer new opportunities for efficient, practical, and selective syntheses

• valuable features, amide derivatives are ubiquitous across the pharmaceutical, agrochemical, dye, polymer, and renewable-energy industries [6][7][8][9][10][11]. Accordingly, the development of efficient methods for both amide-bond formation and the selective transformation of amide functionalities remains

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

• provide the essential carbocation stabilisation (likely via cation–π interactions) and thus facilitate alkyl migration. The resulting 5,7-bicyclic carbocation 14b is further elaborated and decorated by selective oxidation reactions to build up the family of pseudolaric acids. For example, after a second

• enables selective C-4 to C-14 ketone aldolisation furnishing pepluanol D (87). The same authors also proposed a putative biosynthetic origin for the intriguing 5/4/7/3-ring system of pepluacetal (89) from pepluanol A (88) by olefin isomerisation (88a to 88b) and 1,6-conjugate addition to build up the new

• way of selective oxidation at C-17 (possibly through HAT and SET-induced generation of the positive charge as described in other examples above) the C-17-centred carbocation 114a can undergo a cascade rearrangement, consisting of an initial 1,2-methyl migration to 114b, followed by the crucial 1,2

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

• into a general, efficient synthetic strategy that enables an entirely new retrosynthetic logic, and (2) to enable previously inaccessible mechanistic pathways for selective arene functionalization. With this review, we aim to assess the current landscape of synthetically applied systems that achieve

• following sections therefore focus on the selective disruption of aromaticity through the formation of transition metal–arene π-complexes. Transient and reversible coordination of transition metals to aromatic π-systems is a key feature of many catalytic transformations, with the oxidative addition 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

• and selective synthesis of previously inaccessible 4-hydroxyquinolin-2(1H)-one derivatives. Utilizing readily available 6-halo-4-hydroxyquinolinones, aromatic aldehydes, Meldrum’s acid, and alcohols under ʟ-proline catalysis, the reaction proceeds via in situ formation of arylidene-substituted Meldrum

• alcoholysis under prolonged reflux. This insight resolves a long-standing selectivity issue and transforms a known cascade into a synthetically divergent, operationally simple one-pot process. The selective access to methyl and ethyl esters is synthetically valuable, serving as versatile intermediates for

Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF

• Ruiyan Wang and
• Yunan Wu

Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16

• facilitating thermally activated reverse intersystem crossing (RISC) and enabling TADF. Therefore, a molecular platform based on imide is expected to achieve programmable triplet management through a “configuration-decoupling + packing/confinement synergy” strategy. This platform can enable the selective

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

• yield (21%, Table 1, entry 2). When acid (HCl) was added after quenching the residue with water, the yields of products 2a and 3a were increased (30 and 35%, Table 1, entry 3). The selective formation of 2-hydroxy-2,5-dihydrothiophene 2a in 41% yield was achieved when using 5 equiv of sodium and 0.25 mL

• TFE the deacylated product 2a was formed in 75% yield (Table 1, entry 12). Carrying out the reaction under Hockings conditions [26] resulted in the selective formation of the deacylated product 3a (Table 1, entry 13). Thus, the optimized conditions for the synthesis of 2-hydroxy-substituted 2,5

• selective formation of the deacylated products in 60–70% yield. In continuation of the research, isomeric dihydrothiophenes (Scheme 1, E) were also treated in ethanolic solution with sodium ethoxide. Initially, cyclohexano-spiroannulated dihydrothiophene 4a was treated with ethanolic solution (3 mL) in the

Streptoquinolines A and B, new antibacterial meroterpenoids produced by Streptomyces sp. TMPU-A0679

• Akiho Yagi,
• Hitomi Tomura,
• Ami Konno and
• Ryuji Uchida

Beilstein J. Org. Chem. 2026, 22, 185–191, doi:10.3762/bjoc.22.12

• sesquiterpene fused with a highly substituted quinoline moiety. Further structural comparisons and specific rotation data revealed that 1 and 2 were epimers at C-4'. Compounds 1 and 2 both exhibited selective antibacterial activity against Gram-positive bacteria, including VRE and methicillin-resistant

• -type sesquiterpene fused with a highly substituted quinoline unit. These compounds were isolated from terrestrial Streptomyces sp. TMPU-A0679 and both exhibited selective antibacterial activity against Gram-positive pathogens, including VRE and MRSA. Structural and stereochemical analyses established

Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• Copenhagen, Denmark Department of Science and Environment, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark 10.3762/bjoc.22.11 Abstract 25CN-NBOH is a selective serotonin 2A receptor agonist used extensively as a tool compound in preclinical research. Herein, we perform an in-depth

• efficacy [2]. Activation of the 5-HT2AR is thought to induce altered states of consciousness and suppress the default-mode network, a process hypothesized to underlie their clinical benefits [3]. However, classic psychedelics lack receptor selectivity, prompting efforts to develop more selective 5-HT2AR

• agonists to study the effects of solely activating this key receptor [4]. 25CN-NBOH (1) was reported in 2014 as part of a series of ligands in the search for selective 5-HT2AR agonists [5]. Subsequently, it has been used and characterized extensively as a tool for investigations into the effects of

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• similar analogues, using 3 as a key intermediate. Furthermore, we were interested in producing a water-soluble derivative of 1, much like indigo carmine was developed as a water-soluble derivative of indigo. Several syntheses of 3 have been reported, but the most common method involves the selective