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

• to obtain the respective aldehyde and alcohol motifs were accomplished by acidic treatment, then HWE reaction and 1,4-reduction with LiBH4 afforded sulfone 303. The iodination and addition of Zn in AcOH triggered a Bernet–Vasella-type fragmentation (indicated by arrows) towards 304 [108]. Finally

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• selenium-containing systems [51][52]. The ESI-HRMS mass spectral data of compound 7 showed a molecular ion peak [M + H]+ at m/z 544.1407, which is consistent with the calculated m/z value of 544.1385. For compound 8, the observed molecular ion peaks revealed extensive fragmentation of the molecular ion

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

• domino-process consists in nucleophilic addition of the alcohol, mercaptan or water (in case the reaction was performed in CH3CN) at the benzoyl group (Scheme 3). The subsequent ring-opening of the pyrrolidine ring can proceed via two possible pathways. First path is the tandem Grob-type fragmentation

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

• of a nucleophile towards C-12 of 120c ruptures the cyclopropane ring in a fragmentation reaction, kicking out the leaving group at C-14 in the process and expanding the 6-membered C-ring to furnish the final product 121. Finally, an example for a concomitant B/C-ring contraction and expansion was

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

• if applied to non-tumor cells. At the same time, nucleus fragmentation was not observed during the experiment which may indicate the absence of pro-apoptotic activity. Data on actin cytoskeleton structure as well as data demonstrating percentage of cells with filopodia-like deformations and

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

• hydrogenation of a pyridine precursor, whereas Mander’s strategy relied on an Eschenmoser fragmentation as well as a reductive amination (Scheme 17) [87]. Pyridine analogue 121 was converted to tetracyclic compound 123 via a 1,2-addition. A five-step transformation, including allylic hydroxy group transposition

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

• -nitrosopropane (1a) is expected to be barrierless with the formation of N-oxyl radical B. The radical B undergoes very low-barrier (ΔG≠ 5.5 kcal/mol) fragmentation with the release of NO2 molecule and formation of the final product 2a. An alternative pathway for the formation of 2a is a direct NO2 extrusion from

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

• in C14–C15 via a Horner–Wadsworth–Emmons (HWE) reaction. Interestingly, the left-hand fragment is synthesized in an unusual thermal Eschenmoser fragmentation, the product being directly conjoined in a one-pot fashion. First, commercially available (S)-3-methylpiperidine (74) was N-protected and

• furnish 79 in excellent yield. The key connection in this synthesis proceeded in a one-pot fashion in 67% yield. At first, tosylhydrazone 79 was subjected to a thermal Eschenmoser fragmentation at 150 °C under microwave conditions to obtain both, an alkyne and aldehyde moiety in intermediate 80. The crude

• fragmentation, a Horner–Wadsworth–Emmons (HWE) reaction and an alkyne methylation, all proceeding in one-pot. This then set the stage for the key Diels–Alder/aromatization sequence. Although three entirely different approaches are displayed, all three pose a fast 13 or 15 step longest linear sequence access to

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

• compound 19. This intermediate is converted to lactone 20 via base-promoted Grob fragmentation followed by acid-mediated MOM deprotection. Epoxidation of the C10–C11 double bond in 20, lactone hydrolysis-promoted epoxide ring opening, and inversion of the C10 hydroxy configuration, yield the key

• secondary hydroxy group, successfully achieving the conversion of ryanodol (4) to 3-epi-ryanodol (5) and 3-epi-ryanodine (30) [45]. The specific synthetic route is as follows (Scheme 3): Beginning with ryanodol (4), an acid-promoted fragmentation yields anhydroryanodol (10). Subjecting compound 10 to Li/NH3

• 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

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• formyloxy group on the N atom in the unstable intermediate 13 serves as electron-withdrawing group to facilitate fragmentation when removal of the acidic proton at C2 was initiated. Although the reduction of enone 14 could provide the requisite stereoisomer, the rigid conformation of such bicyclic [4.3.0

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• considerable attention in recent decades. Numerous approaches to natural product synthesis have been reported in which a photochemical transformation represents a key step [1][2][3]. In this context, the photochemical [2 + 2] cycloaddition and subsequent fragmentation of the resulting cyclobutane provides a

• leads to ketene D, which can undergo cycloaddition with an alkene to yield E. This fragmentation pathway dominates under various conditions (e.g., transition-metal catalysis, nucleophilic addition) and is driven by ring-strain release [11]. PET, an alternative to direct excitation and EnT, enables the

• -initiated [2 + 2] cyclization of the tryptamine-substituted cyclobutenone K to form the radical cation L, which has a highly functionalized and rigid bicyclo[2.2.0]hexane core. Fragmentation of the C3–C19 bond would afford a redox-active intermediate which upon further reductive quenching would lead to the

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• , particularly iridoids. One of the promising methods for ring contraction in the absence of multiple bonds in the six-membered ring of terpenoids was proposed by Grishko et al. [26] (Scheme 6). The key step of 2,3-fragmentation was the cleavage of an enolized C–C bond at a keto group, followed by an

• -ketoxime 45 by Grignard reduction alkylation, followed by a Beckmann fragmentation of the C2–C3 bond of the intermediate 3-ethyl-substituted hydroxyimino ketone in the SOCl2-CH2Cl2 system. The introduction of a carbonyl substituent into the isopropylidene fragment of ketone 46 was achieved either by

• 147b and 148b. The authors of [74] suggested that keto enol 149 was the intermediate from which the cyclopentane derivative 147 and fragmentation products 148 and 150 were formed. Irradiation of a solution of keto enol 149 in benzene containing 1% methanol resulted in the formation of the proposed

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• favor Norrish–Yang cyclization over the competing unproductive Norrish type II fragmentation pathway; (2) the long excitation wavelength of 1,2-diketones (λmax ≈ 450 nm) enables their selective activation in the presence of other photochemically excitable groups [5][6]. Furthermore, the resulting α

• –Yang cyclization and related photoredox reactions, owing to their ability to undergo selective activation under mild conditions (e.g., long-wavelength irradiation) – a feature that minimizes competing fragmentation pathways. Notably, different dicarbonyl substrates exhibit distinct reactivity patterns

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• dichloromethane (DCM), gold(I)-catalyzed alkyne activation initiated 6-endo-dig cyclization of the conjugated alkene. Subsequent alkyl migration formed four-membered ring intermediate 9, which underwent fragmentation and rearrangement to yield phenanthrene derivative 10 (Scheme 3, path a). When tetrahydrofuran

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• DPG dicarbamates, along with their various fragmentation products. The mass spectra for KSU-1n-Hex and KSU-1C14, show evidence of urea products in negative mode, and protonated DPG carbamates along with their fragmentation products in positive mode (Figures S4–S7, Supporting Information File 1

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• involves an electrooxidative dialkoxylation of the furan ring providing spirocycles 4a–c which undergo a further electrooxidative fragmentation to products 3a–c. However, the further transformation of products 3a–c was hampered by the problematic removal of the protecting groups (Ts, Boc, Ac) under the

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• an alkoxide anion producing an ether (Scheme 2) [35]. Although this seems to be a relatively simple, straightforward reaction, the yields are often low due to the competing Grob fragmentation (Scheme 2) which, besides being entropically favoured, might also be favoured by the thermodynamic stability

• conditions and exhibits excellent functional group tolerance (demonstrated by synthesising a large library of azetidine analogues), but tends to deliver the oxetane products in rather low yields due to fragmentation of the biradical intermediate 67 through a Norrish-type II process. 1.3 [2 + 2

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• a fragmentation process for the total synthesis of (−)-phlegmariurine B. A one-pot epoxidation/nucleophilic epoxide opening introduced both a hydroxy group and a chloride across the cyclopentene, producing 14 in 57% yield. After oxidation of alcohol 14 to ketone 15, the Mukaiyama hydration then

• triggered a Grob fragmentation process of hemiaminal 16 and afforded the imide compound 17. Final regioselective reduction of one of the two carbonyls on the imide completed the synthesis of (−)-phlegmariurine B. Annulation Total syntheses of cephalotaxine and cephalezomine H The [2 + 3] annulation of

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• computational study to design new PCs to be employed in atom transfer radical polymerization (O-ATRP) [17]. Notably, the sulfur-based structure 2 showed excellent performance for this transformation. One year later, the same research group reported its use in a reversible addition-fragmentation chain-transfer

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• derivative 60 is obtained in one step under Ugi reaction conditions following an Ugi reaction/5-endo-dig carbocyclization/retro-Claisen fragmentation cascade reaction (Scheme 47) [110]. Although the reaction is performed under the conditions typically used in Ugi reactions (MeOH, 80 °C), in this case the

• an amide) and the enolizable position favored by the presence of an additional withdrawing group (phenylcarboxy). It was proposed that, after the cyclization, intermediate II follows a retro-Claisen fragmentation to give the final product by releasing

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• bacteriochlorin for photoinduced electron transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization under far-red light (Figure 4) [43]. This synthetic bacteriochlorin, structurally modified from tetraphenylporphyrin with two reduced pyrrole rings, exhibits strong absorption in the far

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• biomolecules like DNA and lipids. Lipid peroxidation and membrane disruption can cause random cross-linking, resulting in cell death and the fragmentation of proteins and enzymes. Elevated concentrations of reactive oxygen species (ROS) from various molecular processes contribute to the oxidation of proteins

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• homolytic fragmentation in solution, producing tetramethylpiperidinyl radical and the TEMPO radical. The tetramethylpiperidinyl radical interacts with 2-naphthol derivatives 58, leading to the generation of an oxygen-centered radical through hydrogen atom transfer, which resonates with its respective carbon

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• the ions that depend on the backbone chain length. The same is true for the respective methyl esters; their mass spectrometric fragmentation is shown in Supporting Information File 1, Figure S12. The natural acids thus form a homologous series ranging from 4,6-dimethylnon-5-enoic acid (A) to 4,6