Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• in the mixture of melifoliones was increased to a maximum of about 10–15%. Since it was not possible to distinguish or even to separate the isomeric melifoliones using chromatographic methods, their quantitative ratio after cyclization of 5 could only be determined using the 1H NMR spectra. After

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

• –Kishi (NHK) coupling and Pd-mediated cyclization. Fragment 31 was synthesized from known precursor 28 [74] in 9 steps via MMTr-protection, replacement of the Bn- with TBDMS-protecting groups, hydroxylation of sulfone 29 to alcohol 30, tosylation, bromide substitution, acidic MMTr-cleavage and DMP

• proved to be suitable for the cyclization towards 35 and the eventual macrocyclization was achieved via coupling of the alkyl bromide unit with the thioester. Mechanistically, this reaction is enabled by the formation of an intermediate alkylzinc halide, which is produced by single electron transfer

• reactions [76][77] for the assembly of fragment 45 (Scheme 6) [78]. Here, 40 and 42 served as the substrates for the allene-Prins reaction towards 43. Notably, the Bz-derivative of 40, 41, served as a starting point for a corresponding halichondrin B analog. The stereoselective course of this cyclization is

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

• ) intermediate, which undergoes intramolecular nucleophilic cyclization (Scheme 15) [54]. This work represents the first synthesis of a compound integrating both helical and axial stereogenic elements, and achieves high diastereoselectivity and enantioselectivity through a cinchona alkaloid-derived squaramide

• organocatalytic approach. The mechanistic study revealed that the reaction proceeds through a stepwise double cyclization process: The first cyclization generates an intermediate bearing a stereogenic axis, while the second cyclization involves dynamic kinetic resolution of the spiral reaction intermediate under

• . Soon after, Shibata and co-workers developed a cycloisomerization strategy that generated various axially chiral polycyclic aromatic hydrocarbons (PAHs) 70 through bond-cleavage followed by successive cyclization reactions with excellent yields and enantioselectivity (Scheme 19) [58]. In 2020, Miller

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

Concept-driven strategies in target-oriented synthesis

• David Yu-Kai Chen,
• Chao Li and
• Yefeng Tang

Beilstein J. Org. Chem. 2026, 22, 451–454, doi:10.3762/bjoc.22.32

• dearomatization (review, Xiangbing Qi and co-worker), enamide cyclization (review, Xiao-Ming Zhang et al.), glycosylation (PI-88, Guothi Xiao et al.), [3 + 2 + 1] cycloaddition (tetrahydrofluorenone, Zhi-Xiang Yu et al.), 1,n-enyne cyclization (review, Maosheng Cheng, Lu Yang, Yongxiang Liu et al.), oxidative

• radical cyclization (prostaglandin D2 metabolite, Jun Huang et al.), reductive cyclization cascade (aglacin B, Jina Xiao, Yu Peng et al.), electrochemical cyclization (review, Bin Li, H. N. C. Wong, Xiao-Shui Peng et al.), photochemical reactions (review, Shao-Min Fu, Bo Liu et al.), carbene insertion

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• with 2,4,6-trihydroxyacetophenone as a starting material undergoing hydroxy protection, α-bromination, construction of α,β-epoxy carbonyl products via the Darzens reaction, acid-mediated deprotection, and cyclization to afford the target compounds. This method is highlighted by satisfactory overall

• -epoxycarbonyl intermediates. The latter undergo simultaneous deprotection and cyclization by treatment with acid to afford the targeted trans-(±)-taxifolin and its derivatives [19][20][21][22][23][24][25][26][27][28][29][30] (Scheme 1a). Although this synthetic route is efficient, a significant drawback is that

• via Darzens reaction. Subsequent acid-mediated deprotection and cyclization then afforded the target compounds. Compared with the widely used method involving peroxides reported earlier, the present method is highlighted with avoidance of the use of peroxides, therefore enabling safe scale-up and

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

• , the treatment with iPrMgBr for preparation of the magnesium alkoxide at highly dilute conditions (10 mM) and sequential cyclization successfully proceeded to provide the C6-iodo-substituted oxacyclophene 1ad in 79% yield. Synthesis of C6-methyl and C6-phenyl-substituted oxacyclophenes The Kumada–Tamao

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

• electrochemical arenol activations reported by Waldvogel and co-workers [46]. Subsequent intramolecular dehydrative cyclization furnishes the desired oxaza[8]helicenes 5. The oxidation-potential gap between 3 and 4 and the reactivity of Int-I thus provides a handle to control chemo- and regioselectivity

• 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

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• literature data on reactivity of 5-azidopentyne derivatives in intramolecular Huisgen cycloaddition reactions are contradictory. Some authors successfully obtained 5-azidopentyne derivatives upon nucleophilic substitution at 80 °C in DMF, and additional heating at 170 °C was necessary for cyclization to

• dioxide in tetrahydrofuran gave vinyl ether 8, which was isolated with 50% yield (Scheme 4). The structure of the product 8 was confirmed by X-ray crystallographic analysis (Figure 3, CCDC 2512653). Formation of 8 apparently occurs via cyclization of alkynal 7. The formation of vinyl ethers has been

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

• by intramolecular cyclization to yield a lactone, which undergoes decarboxylation to produce the corresponding azomethine ylide. In our system, we propose this generated ylide reacts with N-substituted maleimides 3a–p such that the transformation predominantly proceeds via the endo-TS, leading to

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

• formation of the cyclic lactone, which predominated under such conditions. These findings suggest that intramolecular attack by the quinolinone OH group, leading to cyclization and formation of pyranoquinolinone, proceeds faster than nucleophilic attack by the external alcohol. Thus, under mild or brief

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• bromine. The cyclization step from this conformation leads to trans-cyclopropanes. X-ray diffraction analysis data for compounds 2, 3, 9a, and 9b convincingly confirm the accepted structures, the position of cyclopropane protons, and the relative configurations of asymmetric atoms (Figures 2–5). It should

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

• rearrangement and Lewis acid-promoted acetal–ene reaction provided the tetracyclic skeleton 101. With 101 in hands, a 6 step transformation afforded the alkyne 102 in an overall yield of 45%. After obtaining 102, the authors used a free radical reaction to initiate a one-step 6-exo-trig cyclization

• addition to indirectly reduce the heteroaromatic ring of the isoquinoline to yield compound 118. This was followed by desilylation with TBAF and spontaneous intramolecular cyclization to yield the tricyclic 119. With 119 in hand, the double bond was diastereoselectively hydrogenated using Et3SiH and TFA

• sustained interest from synthetic chemists worldwide due to their pronounced antibacterial and anticancer properties. Since their discovery, bis-THIQ scaffolds have been constructed primarily through the Pictet–Spengler reaction, a cyclization strategy that continues to be widely employed in total synthesis

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

• Hiroshige Ogawa and
• Hugh Nakamura

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

• -mediated stoichiometric radical reactions Traditionally, the use of Zr complexes in organic reactions had been limited to two-electron processes; however, the first example of a Zr-mediated radical reaction was reported by Oshima et al. in 2001. They reported an intramolecular radical cyclization using

• background of zirconium and its physical properties. Image depicted in the background of Figure 1 was purchased from iStock.com/Just_Super. This content is not subject to CC BY 4.0. Zr-mediated radical cyclization. Ni/Zr-mediated one-pot ketone synthesis. Zirconocene-catalyzed alkylative dimerization of 2

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

• anion). Generation of tertiary aliphatic cations and intramolecular trapping with alkenes or alkynes is well known in the context of polyene cyclizations [155]. Building on Johnson’s earlier work (Scheme 48A) [156], Fañanás and Rodríguez developed an intramolecular cationic cyclization strategy to

• systems, with no successful extension to other ring sizes. The proposed mechanism involves initial generation of a tertiary or benzylic carbocation, followed by intramolecular cyclization with a pendant alkyne to furnish a vinyl cation intermediate. This species is postulated to be trapped by the solvent

• , potentially forming a transient chloronium ion (CH2Cl+). Reaction of this electrophilic intermediate with the BF4− counterion would be expected to yield CH2FCl and BF3; however, the authors did not investigate or confirm the formation of these by-products. In 2006, Cook reported a related cyclization

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

• relatively simple structures, we considered two basic approaches to 4-, 5-, 6-, and 7-prenylated tryptophans as synthetic precursors which could be converted to the intended natural products by cyclization to benzodiazepine-2,5-diones or diketopiperazines. First, is the evident use of tryptophan as a

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

• , 620066 Ekaterinburg, Russian Federation Saint-Petersburg Pasteur Institute, Mira St. 14, 197101 Saint-Petersburg, Russian Federation 10.3762/bjoc.21.209 Abstract The use of 1,3-diamino-2-propanol with competitive N- and O-nucleophilic centers in a three-component cyclization with ethyl 4,4,4

• methyl ketones increases the regioselectivity in the synthesis of octahydropyrido[1,2-a]pyrimidinones. The cyclization with acetophenone is characterized by the regiospecific generation of these bicycles. The presence of three chiral centers in the synthesized bicycles, depending on the alkyl substituent

• -component cyclization; Introduction The modern strategy of organic synthesis is aimed at conforming to the "green chemistry" principles based on PASE (pot, atom, step, economic) methods. These principles serve as the foundation for multicomponent processes that allow various structurally complex molecules

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• trifluoromethylated isothiazolium thiocyanates and 4-thiocyanato-2,5-dihydrofurans is presented through hydrothiocyanation/cyclization of CF3-iminopropargyl alcohols using NaSCN in AcOH/MeCN. The formation of the two products can be explained by different directions of cyclization of the primary adducts of thiocyanic

• , thioethers, disulfides, phosphonothioates, and trifluoromethyl sulfides. Additionally, due to the presence of two electrophilic sites (the sulfur atom and the carbon of the nitrile function), thiocyanates can readily undergo domino-type intramolecular cyclization reactions to form heterocycles. So, if a

• thiocyanate group is introduced into a molecule bearing a nucleophile in a suitable position, cyclization can readily occur. In recent years, several methods for the hydrothiocyanation of alkynes bearing functional groups, primarily alkynoates, have been developed. Thus, thiocyano enoates were synthesized via

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

• , hydroboration/oxidation, and an oxidative cyclization protocol. The diastereomers were separable by column chromatography, leading to this faster and more scalable procedure to be performed preferentially over a six-step diastereoselective sequence. After silyl ether deprotection, the Wagner–Meerwein-type

• –halogen exchange in the ABC-fragment 38 followed by 1,2-addition to the ketone moiety in the F-ring fragment 42. Protection group manipulations allowed for the union of both fragments to advanced intermediate 43 in three steps in 42%, setting the stage for the key cyclization reactions in this sequence

• . Compound 44 could then be subjected to a Nazarov cyclization, which was performed in a photochemical fashion, to close ring C. Further reduction and hydrogenation in ring D and an acid-induced spirocyclization of Nazarov-product 45 concluded the synthesis of cyclopamine. Notably, this total synthesis of

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

• step for the construction of the ring systems has been implemented by an intramolecular Friedel–Crafts cyclization. Altogether eight new ring systems are described here, five of them are also characterized by single-crystal X-ray diffraction. Keywords: acylation; bridged derivatives; cyclization

• followed by basic hydrolysis afforded carboxylic acids 14 and 15. Ring closure of the latter compounds to tetracyclic derivatives 6 and 7 was carried out in one pot by SnCl4-catalyzed Friedel–Crafts cyclization of the acid chlorides obtained via reaction of 14 and 15 with phosphorus pentachloride. In the

• reaction of compound 15, regioisomer 8 was also isolated in 2% yield, which represents a new ring system, too. It is interesting to mention that the formation of a similar isomer was not observed in the cyclization reaction of compound 14. The same disparity was observed in the studies of electrophilic

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• strategy for the total synthesis of segetalins A–H, J and K (1–10), bioactive cyclopeptides isolated from Vaccaria segetalis. Linear precursors were assembled on cost-effective 2-chlorotrityl chloride resin via Fmoc-SPPS, followed by PyBOP-mediated head-to-tail cyclization in DMF (10−3 M). After RP-HPLC

• scalable methodology overcomes limitations of prior syntheses, enabling biological evaluation. Keywords: Fmoc-solid-phase peptide synthesis (Fmoc-SPPS); head-to-tail cyclization; plant cyclopeptides; Vaccaria segetalis; Introduction Cyclopeptides have garnered significant research interest owing to their

• unique conformational constraints imposed by cyclization and diverse biological activities [1][2][3]. Specifically, plant-derived cyclopeptides represent a valuable source of potential lead compounds for drug discovery [4]. Segetalins A–H, J and K (1–10), isolated from the seeds of Vaccaria segetalis

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

• -attached ketyl radical B are generated under photoredox NHC catalysis under visible-light irradiation. The 5-exo-trig radical cyclization of the alkene-tethered iminyl radicals A furnished a dihydropyrrole-derived radical coupled with the NHC group attached ketyl radical B. This approach features readily

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• substructure hidden inside the natural product’s cage-like ring system, Kalesse’s group chose to construct this architecture first using a tandem Nazarov/ene cyclization [36]. The cis-pentalene was subsequently assembled via a Ti(III)-mediated epoxide–ketone coupling reaction. Starting from the known

• deprotection and oxidation of the secondary alcohol, yielded the cyclization precursor 35. A B(C6F5)3-catalyzed tandem Nazarov/ene cyclization of 35 provided the key spirocyclic intermediate 37. The tertiary alcohol was protected in situ with TESOTf to suppress retro-aldol side reactions. Notably, prior TES

• deprotection of the cyclization precursor was essential, as the TES-protected analogue of 35 failed to deliver the desired spirocycle 38 under the Nazarov cyclization conditions. α-Oxidation of 38 with molecular oxygen afforded 39, which was then converted to 40 via formation of a chloromethyl silyl ether

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• intermediate 21, thereby completing the construction of the D ring. Adjustments of functional groups and oxidation states at multiple sites then afford anhydroryanodol (10). Finally, epoxidation of the C1–C2 double bond followed by Li/NH3-promoted reductive cyclization constructs the E ring of the molecular

• conditions induces the first intramolecular reductive cyclization, affording hemiacetal 27. This intermediate is then transformed via a one-pot sequence involving epoxidation, fragmentation, and re-epoxidation to give epoxide 29. A second intramolecular reductive cyclization of 29 under Li/NH3 forms the

• of (+)-ryanodol (4) in just 15 steps, highlighting the Pauson–Khand cyclization and a selenium dioxide-mediated selective oxidation as key transformations [48] (Scheme 7). To construct the multi-substituted five-membered ring in the target molecule, the authors strategically employed the Pauson–Khand

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• Abstract The total synthesis of bioactive (+)-aglacin B was achieved. The key steps include an asymmetric conjugate addition reaction induced by a chiral auxiliary and a nickel-promoted reductive tandem cyclization of the elaborated β-bromo acetal, which led to the efficient construction of the

• synthesis of both enantiomers of aglacins A (1), B (2), and E (4) by asymmetric photoenolization/Diels–Alder reactions as the key steps for the construction of the C7–C8 and C7′–C8′ bonds [8]. During the past decade, we had developed nickel-catalyzed or -promoted reductive coupling/cyclization reactions for

• cyclization, and a subsequent acetal reduction under acidic conditions then can complete the total synthesis of this molecule. The cyclization precursor 5 could be prepared from the primary alcohol 6 through transforming functional groups of the alkyl chain and installing an allyl group. It was envisioned