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

• C1–C13 fragment 11 with C14–C35 fragment 12 [66][67][68]. Despite these great advances, still, the research on improving synthetic efficiency, reducing production costs, omitting toxic chemicals, as well as on new pathways towards 1`s 4 heterocyclic precursor fragments is rigorously ongoing [69][70

• . Here, 121 bears the right configuration needed for Halaven synthesis, but the authors also showed that 122 was easily converted to 121 via Mitsunobu inversion. Although 121 only represents a small building block for the total assembly of 1, this method especially stands out for its cost-efficiency and

• competitive reaction sequence for the large-scale process currently applied by Eisai [66]. Furthermore, this method stands out for its cost-efficiency, since only an enantiomeric pair of ruthenium catalysts is needed in addition to other standard chemicals. A similar building block as from Kaghad and co

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

• % yield. Its structure was confirmed by 1H NMR, 13C NMR, and HRMS. The uranium(VI) extraction efficiency of PCP HA was evaluated by solid–liquid extraction experiments, using uranyl acetate as the uranium source, with measurements performed by gamma spectroscopy. PCP HA demonstrated good performance

• , removing up to 95% of uranyl(VI) from aqueous solutions (1 mM) at acidic pH, likely due to the strong coordination provided by its hydroxamic acid groups. Further studies revealed that the extraction efficiency also depends on the ligand-to-metal molar ratio. These findings establish PCP HA as a promising

• solid–liquid approach as previously described for calixarenes [58]. Extraction experiments In this study, two parameters that can influence the solid-liquid extraction efficiency of PCP-HA toward uranyl, namely pH and ligand-to-metal ratio, were studied. To ensure comparison between extraction

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

• one chiral axis followed by the second, and transformation from central chirality to axial chirality. We anticipate that this review will facilitate the development of novel synthetic strategies for remote biaxial chiral molecules, improve asymmetric synthesis efficiency, and expand their applications

• [41]. This strategy delivered excellent enantioselectivity, diastereoselectivity, and overall efficiency, underscoring its unique advantages in the synthesis of multiaxially chiral scaffolds. In parallel, Tanaka and co-workers advanced a [2 + 2 + 2] cycloaddition strategy to realize an asymmetric

• diastereoselectivity. Notably, this system overcame the limitations of previous methodologies that required elevated temperatures and suffered from poor efficiency and narrow substrate scope. Later, in 2011, the group extended this approach using a bisphosphine-ligated rhodium complex to efficiently synthesize

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

• complex organic architectures have witnessed remarkable achievements in recent years, continuously redefining the boundaries of creativity, efficiency, and practicality. On the other hand, it has been suggested that the field of complex molecular assembly is transitioning (or ought to transition) from an

• advancements, and strategic innovations. However, while efficiency and practicality remain essential design considerations in targeted synthesis, it is worth pondering whether the pursuit of efficiency (along with its associated elements) truly captures the underlying scientific essence of target-oriented

• , a generalized approach can address multiple target classes simultaneously, but typically exhibits reduced efficiency as molecular complexity increases. Integrating elements from both a customized and a generalized approach may represent an “ideal” strategy, although achieving such integration

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

• (1.2 equiv) was performed in CH3CN, using t-BuOLi (1.2 equiv) as base in the presence of a catalytic amount of ZnCl2. Due to the high efficiency of the reaction, no purification of product (±)-4a by column chromatography was necessary after post-treatment and the product could be directly used in the

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

• macrocyclic core through simple acylation of p-aminocalix[4]arenes with the respective phosphorous-containing activated esters. Such grafting of well-known receptor units onto a common platform has led to substantial amplification of the efficiency of lanthanide and actinide extraction from acidic media by

• propargylated and 2-azidoethylated calix[4]arenes revealed their enhanced efficiency, resulting in the preferential formation of exhaustively triazolated macrocycles over mixed triazolated/propargylated or triazolated/2-azidoethylated ones [79][80]. Furthermore, it has been proved that triazolated calixarenes

• next the TBS-protecting groups were removed from the acetylene units in the Boc-protected tetraamines 21–23 (Scheme 4). For the removal of the TBS groups, instead of using an equivalent amount of n-Bu4NF, it was used as a catalyst in a water/THF mixture, which showed excellent efficiency for the room

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

• frontier orbitals, intermolecular interactions, and excited-state dynamics, frequently enhancing fluorescence efficiency and circularly polarized luminescence (CPL) [16][17][18][19][20][21][22]. Consequently, heterohelicenes have emerged as attractive platforms for optoelectronic devices, 3D displays

• Supporting Information File 1), we developed a one-pot electrochemical annulation between 3 and β-naphthol derivative 4. Using n-Bu4NPF6 as the electrolyte in CH2Cl2 at room temperature, this protocol furnished oxaza[8]helicenes 5 in good-to-moderate yields with >75% Faradaic efficiency, and no homo-coupling

• with the observed trends in emission efficiency. Fluorescence quantum yields (Φf, in chloroform, 1 × 10−3 M) for 5a and 5b were 25.1% and 22.6%, slightly lower than those of 6a (40.5%) and 6b (38.9%). This difference can be rationalized by their radiative rate constants (kf). The calculated kf,calcd

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

• (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

• secondary 2-iodo-N,N-dimethylbenzamides 69–71 afforded 2,2,2-trifluoroethyl 2-iodobenzoate (68) in moderate yield. Higher yields were observed when tertiary amides 72 and 73 were employed for esterification. Among these, pyrrolidine-based amide 73 exhibited the highest efficiency, furnishing the ester 68 in

• N,N-dimethylamides possessing primary, secondary, and tertiary alkyl moieties at the α-position, furnishing the corresponding amides 86–89 in good to high yields. The efficiency of transamidation decreased with increasing steric congestion. Mechanistically, the carbonyl group is first activated by

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

• nitroxides are incorporated into macromolecular or nanosized supramolecular structures, which modulate nitroxide properties. For example, the efficiency of ORCA (relaxivity) directly depends on the rotational correlation time of the radicals attached to the scaffold [13][14][15]. Large structures in which

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

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

• , lifetime, and efficiency, make them highly versatile for integration into advanced optoelectronic devices [9][10][11]. The performance limits of these devices, particularly in terms of their brightness, longevity, and efficiency, are largely dependent on the ability to precisely control the dynamics of the

• the excitons within the crystal, thus facilitating the generation of room-temperature phosphorescence. The presence of these intermolecular π–π interactions enhances the efficiency of phosphorescence by providing a stable environment for the triplet excitons, which are otherwise prone to non-radiative

• increases the number of possible ISC pathways but also plays a crucial role in facilitating the efficient intersystem crossing process. This suggests that the intermolecular interactions in the solid-state environment are key factors in controlling the efficiency of the triplet exciton utilization

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

• slightly lower yield (88%, Table 1, entry 6). The organic base Et3N afforded 3a in 89% yield (Table 1, entry 7). These data indicate that mild inorganic bases are generally more appropriate for this transformation, with NaHCO3 offering the best combination of efficiency and practicality. Moreover

• diminished yields (68% and 88%, respectively; Table 1, entries 9 and 10). We tentatively attribute the inferior performance of NCS to its lower halogen-transfer efficiency and oxidation potential under the present conditions, which likely result in a less efficient generation of the key electrophilic sulfur

• species and in increased competitive decomposition. In contrast, the more strongly oxidizing TCCA tends to promote non-productive overoxidation pathways, thus also failing to match the efficiency of NBS. These results underscore the critical role of halogen source and oxidative strength in modulating 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

• Luminescent materials based on metal complexes have been extensively studied due to their high phosphorescence efficiency, making them promising candidates for applications in organic light-emitting diodes (OLEDs) [1][2][3][4][5], sensors [6][7][8][9], and bioimaging materials [10][11]. Among these materials

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• ) efficiency [14][15][16]. Indanones are highly conjugated with a planar structure, which favors overlap between the molecules. They are building blocks for many compounds, such as organic materials for optoelectronic and NLO applications [17][18]. Research shows that the absorption wavelength of the region

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

• , isoquinoline, pyridine, and related substrates can now be reduced with high efficiency and stereoselectivity, providing efficient access to saturated and partially saturated architectures vital to synthetic chemistry. Furthermore, catalytic asymmetric aromatic hydrogenation has facilitated the asymmetric total

• center and complicate catalysis. Consequently, designing cost-effective catalytic systems with enhanced efficiency, particularly for the selective hydrogenation of complex substrates, remains an essential direction for future research [33]. Hydrogenation of arenes has rapidly evolved from a specialized

• , Aggarwal and co-workers reported a concise and enantioselective synthesis of (−)-finerenone via an asymmetric hydrogen atom transfer (HAT) strategy, completing the total synthesis in just six steps with high efficiency and stereoselectivity [94]. Starting from the 2-pyridone derivative 178, the authors

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

• reported a closely related transformation building on the earlier work by Melloni (Scheme 41) [144]. The final example in their study (compound 229) illustrates that reactions involving aliphatic alkynes proceed with low efficiency and poor yields under these conditions. Notably, Mayr demonstrated that

• electronic attributes. Further improvement of the reaction was achieved by fine-tuning the Mo-metathesis catalyst (Scheme 60A–C). Schrock and Hoveyda also demonstrated that adding small amounts of HB(pin) helps remove residual water, significantly enhancing the reaction efficiency [193]. This technique can

• (Scheme 62B). Systematic optimization studies revealed that additives, such as magnesium bromide etherate or HMPA, had a pronounced impact on both reaction efficiency and stereoselectivity. In 2005, Yan reported that the direct oxidative addition of chloroform to a Mg–TiCl4 bimetallic system generates a

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

• substrate for methylation, affording O-methyl ethylmaltol (9c) in moderate yield (45%, Table 2, entry 3). Subsequent O-demethylation of 9c to ethylmaltol (1) was achieved with boron tribromide in dichloromethane in 65% yield. While an O-methyl group proved successful, the unsatisfactory overall efficiency

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

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

• will not be shown separately. For an example for this color coding, the (−)-englerin A (11) synthesis of the Christmann group is displayed in Scheme 3, together with the symbol explanation mentioned above [12]. This visual aid helps identifying the convergency and efficiency of synthetic routes, as

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

• overall synthetic efficiency of this route. Therefore, the development of more efficient syntheses of rhodexin A is of great significance. Recently, chemoenzymatic syntheses of steroids have made excellent progress, which can enormously shorten the synthetic routes and increase the overall efficiency [23

• -reduction of the butenolide motif. The low efficiency of this reaction prompted us to pursue an alternative two-step approach. First, we performed the deprotection to remove all the Bz groups of 16 by NH3/MeOH, furnishing the saccharide 17 in 95% yield. Eventually, the quick stereospecific C11 carbonyl

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• [52], acetic acid [53], or solvent-free processes [54]. Ionic liquids, such as [Bu4N][OH] [55], [bmim][OH] [56], and [Et3NH][HSO4] [57], and deep eutectic solvents (DES) [58] have been introduced to improve efficiency. Traditional methods for synthesizing these compounds, however, face several

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

• from the high cost of the specialized resin and large solvent volumes required for dilution, coupled with DPPA's poor efficiency in forming sterically hindered peptide bonds involving residues like Val or Ile. Dahiya and Kaur synthesized segetalin C (3) via a solution-phase fragment coupling strategy

• and solid-phase approaches are viable for peptide synthesis, Fmoc-based SPPS offers distinct advantages in operational simplicity and efficiency for laboratory-scale production [20]. We therefore devised a streamlined solid-phase strategy for synthesizing the Vaccaria segetalis cyclopeptide family

• sequences, coupling efficiency was significantly enhanced using a 1:1 mixture of 1-hydroxybenzotriazole (HOBt) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) in DMF [23]. Finally, we obtained crude linear peptides with 75% to 95% yields (Table 1). The critical head-to

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• . Next, we evaluated the efficiency of the SG-NHCO-BU1 material in sorbing dicyanoaurate. First, we showed that SG-BU1 is stable under the experimental conditions (Supporting Information File 1, Figure S5C) and next, we investigated both materials for dicyanoaurate sorption. Thus, we gradually increased

• , exhibiting near-quantitative binding at millimolar concentrations [17]. The lower binding efficiency of BUs attached to the material compared to the free macrocycle in solution can likely be attributed to the heterogeneous nature of the solid-phase system. Moreover, the anion binding ability of BU1 may be

• [17]. The finding is also in agreement with our reported results on the noncovalent SG-BnBU system, which showed significantly higher sorption efficiency towards dicyanoaurate over dicyanoargentate [14]. We next examined the recyclability of the materials. Only SG-NHCO-BU1 was used in these

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

• and the acylazolium complex B (Ep = −0.81 V vs SCE), single-electron transfer (SET) reduction of B was thermodynamically feasible; however, the efficiency was found to be significantly low. The oxidation potential was measured to be around [Ep = +0.72 V] vs SCE, indicating that it is sufficiently

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

• enhance synthetic efficiency, reduce costs, and provide robust solutions to challenges encountered in the synthesis of complex molecular architectures. Ryania diterpenes are natural products characterized by intricate structures and high oxidation states. Biological studies have revealed that the family

• employed therein while providing an in-depth analysis of the innovation of classical methods, the application of emerging technologies, and the enhancements in synthetic efficiency achieved through multi-strategy integration. The aim is to offer readers a clear understanding of the developmental trajectory

• the simultaneous construction of four quaternary carbon centers (C1, C4, C5, and C12) and the core AB bicyclic skeleton, markedly improving synthetic efficiency. Subsequent oxidative desymmetrization of the C14–C15 olefin in (±)-33 established the sterically hindered C11 quaternary carbon center. An α