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

• , reaction with alkaline Lugol’s solution yielded the mono-iodized isomers of both melifolione A (8) and melifolione B (9), identified by their NMR spectra (Figure 2). Reaction with iodosobenzene diacetate – a typical reagent to form para-quinols from phenols [8] – yielded small amounts of a substance, that

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

• 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

• conditions, which led to a cyclization, and benzylated with BnBr towards 321. Stereoselective Michael addition of a Gilman reagent yielded 322. Reduction of the lactone unit yielded a lactol, which is in equilibrium with acyclic aldehyde and alcohol. The aldehyde was trapped via HWE reaction and the obtained

• . AcOH, H2O, rt; ii. NBS, NaHCO3, NaOAc, THF, H2O, 0 °C; iii. acetic anhydride, pyridine, DCM, 0 °C; (e) i. allyl-TMS, BF3·OEt2, MeCN, −10 °C; ii. DDQ, DCM, H2O; (f) i. DMP, NaHCO3, DCM, rt; ii. NaBH4, DCM, MeOH, −78 °C; iii. Stryker’s reagent, toluene, rt; iv. (±)-CSA, MeOH, 60 °C; (g) acetic anhydride

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

• 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

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

• (to ≈1 M), reducing the content of acetic acid in the mixture (to 1 mol per mol of HNO3) and extending the room-temperature reaction time to 72 h. Yet, under these conditions, the desired calix[4]arene 11 was obtained in only 31% yield (Scheme 2), and further variations in reagent excess/concentration

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

• electrophilic benzylating reagent (Scheme 7) [55]. DPT-BM functions as an O-benzylating reagent that generates benzyl cation equivalents upon dissolution in the solvent under non-acidic conditions. Thus, the reaction of an amide with DPT-BM is proposed to form a benzyl imidate salt J, which subsequently

• (SO2F2) was demonstrated to be a powerful electrophilic reagent for amide-bond cleavage by Qin et al. (Scheme 8) [56]. Under an atmosphere of SO2F2, esterification of tertiary amides 28, 35–37 smoothly afforded esters 34 in high yields, although the efficiency was reduced when a bulky substituent was

• 2.2 equivalents of 2-bromopyridine as a base, pyrrolidine-derived amides 38 were effectively activated. Subsequent addition of NFSI as the electrophilic fluorinating reagent, along with alcohols as the nucleophile, afforded the corresponding esters 39–43 in moderate yields. Mechanistically, the

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

• of 9a. The yield of 9b in this reaction depends on excess of the reagent. Heating of 9a with five equivalents of MsCl and excess of DIPEA afforded 9b in 65% yield. When a 1.5-fold excess of mesyl chloride per hydroxy group was used, another nitroxide 9c was isolated in 26% yield along with 9b (43

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

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

• esterification of acids 11a–c afforded the isopropyl esters 12a–c in 71–98% yields. Similar attempts were made using cyclohexyl alcohol both as reagent and solvent in Fischer–Speier esterification; however, difficulties in purifying the reaction mixtures due to the large excess of alcohol prevented isolation of

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

• ). Acetonitrile (Ph. Eur.), absolute ethanol (Reag. Ph. Eur.), ethyl acetate (HPLC grade), dichloromethane (HPLC grade), ammonia (25%, analytical reagent grade), and diethyl ether (reagent grade) were purchased from VWR (Radnor, PA, USA). Sodium hydrogencitrate sesquihydrate (99%), salicylaldehyde (≥98

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

• -bromo-2-nitrobenzaldehyde (4), which can then be directly converted into 1. However, oxidation of the tolyl methyl group into an aldehyde has proved an ongoing challenge. Several syntheses have used a chromium(VI) oxidation to yield the desired product, but the toxic nature of this reagent and the

Design and synthesis of an axially chiral platinum(II) complex and its CPL properties in PMMA matrix

• Daiki Tauchi,
• Sota Ogura,
• Misa Sakura,
• Kazunori Tsubaki and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2026, 22, 143–150, doi:10.3762/bjoc.22.7

• optoelectronic applications. Experimental General information All reagents and solvents were of commercial reagent grade and used without further purification. Dichloromethane for spectroscopy was purchased from FUJIFILM Wako Pure Chemical Corporation. All compounds were identified by 1H , 13C NMR and ESI-MS. 1H

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

• by several approaches: forming of the CF3-group in a nitrocyclopropane (reaction of 2-nitrocyclopropanecarboxylic acid with sulfur tetrafluoride [31][32]), cyclopropane formation from a nitroethene substrate and a CF3-containing reagent (Corey–Chaykovsky reaction [33]), as well as reactions involving

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

• -methylaspidospermidine (Scheme 27) [95][96]. In a single-step reaction, pyridine 182 was activated with 2-chloroethyl triflate and the resulting pyridinium salt was dearomatized with a Grignard reagent to produce ketone 184. In this step, the Grignard nucleophile added regio- and diastereoselectively at the 2-position

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

• . Zirconium was first discovered by Klaproth in 1789 and subsequently isolated by Berzelius in 1824. In 1952, Wilkinson and Birmingham synthesized zirconium-containing organometallic compounds, pioneering research in organozirconium chemistry [2]. In 1974, Schwartz et al. reported the Schwartz reagent, which

• Schwartz’s reagent (Scheme 1) [7][8]. When compound 2, bearing an alkyl halide and an olefin moiety, was treated with triethylborane and Schwartz’s reagent in tetrahydrofuran, a halogen atom transfer (XAT) occurred at the alkyl halide, generating alkyl radical 3. This radical subsequently underwent

• , Schwartz’s reagent reacts with triethylborane to generate a low-valent zirconium complex 5. This complex abstracts the halogen atom from the alkyl halide, forming alkyl radical 8. The radical then cyclizes onto the olefin, and the resulting radical intermediate undergoes hydrogen atom transfer (HAT) from

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

• direct i-substitution. Conclusion Umpolung reactivity of electron-deficient hexa(methoxycarbonyl)cycloheptatriene through its antiaromatic anion allows to introduce a connection between the cycloheptatriene core and an electrophilic reagent. The cycloheptatrienyl anion mainly exists as a conformer with

• further transformation in the case of allylation. Reactions with diazonium salts mainly involve a vicinal addition of the reagent to the anion and subsequent 1,5-sigmatropic shift, 6π-electrocyclization, and azocyclopropane rearrangement into dihydroindazole derivatives. Analysis of the reaction

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

• corresponding alkyne 50 by elimination with LDA were achieved in superb yields (Scheme 10). Gross and Gloede introduced catechol–PCl3 as an effective reagent for the conversion of ketones to the corresponding alkenyl chlorides [62] (Scheme 11A). Hudrlik later demonstrated that, in the case of 2

• -methylcyclohexanone (54), this reagent markedly alters the product distribution compared to PCl5 [63] (Scheme 11B). However, since the reaction conditions differ significantly, it remains unclear whether the product distribution is driven by the reagent itself or by the reaction conditions employed. In 2007, Prati

• -workers reported the serendipitous discovery that N-acyl-2,3-dihydro-4-pyridinones react with the Vilsmeier reagent to afford the corresponding alkenyl chlorides (Scheme 14) [67]. Notably, dihydropyridones failed to react with POCl₃ in the absence of DMF. In 2003, Wähälä reported a closely related

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

• overcome existing constraints in functional group compatibility, efficiency, and reagent scope. In this regard, the direct formation of nitrogen-nitrogen or nitrogen-oxygen bonds presents a significant challenge due to the variety of possible side processes and the low thermodynamic driving force for N–N

• group developed a one-step electrochemical approach to the synthesis of nitro-NNO-azoxy arenes employing ammonium dinitramide (ADN) [87]. The achieved use of ADN, known as prospective chlorine-free green oxidant for aerospace propulsion applications [89][90][91], as both a reagent and an electrolyte is

• compounds with ammonium dinitramide, leading to efficient formation of the nitro-NNO-azoxy group. The developed strategy involves performing the electrosynthesis in an undivided cell under high current density with ADN employed as both a reagent and an electrolyte. The synthesized aliphatic nitro-NNO-azoxy

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

• product 11 in 37% yield (Scheme 2). Despite the modest yield, product 11 was transformed to the corresponding tertiary alcohol 12. Removal of the N-Piv group and dehydration with the Burgess reagent [35] led to an inseparable mixture of olefins slightly in favor of the exo-olefin isomer. Dehydration in

• -methylindole [41] in excellent yields. The Negishi cross-coupling reaction with the organozinc reagent prepared from iodoalanine derivative (vide infra) has been used to prepare various aryl-substituted tryptophans in 76–96% yields [42]. In principle, this protocol should be applicable to all the C4–C7

• amino acid reagent that could be removed under non-acidic conditions after the cross-coupling reaction. To this end, we prepared iodo N-Fmoc-ᴅ-alanyl anthranilamide methyl ester 29 from ᴅ-serine. Treatment of prenylindoles 14–17 with iodine and KOH followed by acetylation afforded the corresponding

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

• trifluoroacetoacetate (1) with methyl ketones 2. This reagent has alternative N- and O-reactive centers and thus can react as an N,N- or N,O-dinucleophile, generating in a single synthesis trifluoromethyl octahydropyrido[1,2-a]pyrimidin-6-ones or hexahydrooxazolo[3,2-a]pyridin-5-ones, or both that contain an additional

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• their versatility, eco-friendliness and low cost, the organo hypervalent iodine reagents have become popular in the field of synthetic chemistry in the last few decades. Hydroxy(tosyloxy)iodobenzene (HTIB) is a hypervalent iodine(III) reagent that contains both a hydroxy and a tosyloxy group. Oxidative

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

• 3-position, a copper-mediated C–H activation of position 12 and subsequent protection of the introduced hydroxy moiety to give compound 25 (Scheme 6). Installation of the lactone moiety in 22 was carried out in a three-step sequence via a 1,2-addition of organocerium reagent 26 to the ketone

• manipulations were carried out, the double bond isomerized to position C5–C6, and a reduction was performed, all in an optimized three-step, scalable sequence. Alkylation with phosphonate reagent 36 and subsequent Horner–Wadsworth–Emmons (HWE) reaction formed ring C, followed by an enolate alkylation to forge

• regioselectively desaturated to furnish known phenylsulfonylenamine (Scheme 23). Conversion toward the bromohydrin, treatment with potassium hydride, and subsequent addition of the crotyl-Grignard reagent 75 gave the desired isomer 76 in 22% yield over four steps. More exactly, the diastereomeric piperidine was

Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• reagent [20], the key intermediate 8 bearing a butenolide motif was obtained in 76% yield. Next, with the aid of the strong Lewis acid Bi(OTf)3, the regioselective elimination of 8 was achieved to produce the Δ14 olefin intermediate 9 in 86% yield. Afterwards, we evaluated the reactivity of 9 towards

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

• , successful macrocyclization was achieved by employing benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) as the coupling reagent in DMF at a concentration of 10−3 M. After cleavage from the resin and global side-chain deprotection, the crude cyclic peptides were purified by preparative

• reagent for the challenging head-to-tail macrocyclization step under moderate dilution (10−3 M). This protocol afforded the target cyclic peptides in practical isolated yields (45–70%) and high purity. Comprehensive structural characterization by HRESIMS, NMR, and HPLC confirmed the identity and high

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

• route commenced from (−)-pulegone. After introducing oxidation states at C6 and C10 and installing an alkynyl group at C11, oxidative cleavage of a double bond yielded the key propargylic alcohol intermediate 66. This compound underwent a 1,2-addition with alkynyl Grignard reagent 67, and the resulting

• , and introduction of an isopropenyl group afforded compound 75. Subsequent protection of the vicinal diol as a boronic ester and diastereoselective reduction of the C3 carbonyl group yielded compound 76. Esterification with acylating reagent 77 under basic conditions, followed by boronic ester removal

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

• asymmetric conjugate addition was carried out [20][21]. The in situ generated aryl–copper(I) species was obtained under the action of CuBr·Me2S with Grignard reagent 8, and then added to a THF solution of the α,β-unsaturated acyl oxazolidinone 7 at −48 °C. This reaction demonstrated an excellent