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

• conformation, causing the nuclei on each side of the molecule to experience different local magnetic environments. In this case, four smaller peaks – each corresponding to a distinct carbon atom – should be observed. The absence of these peaks could be explained by longer relaxation times associated with the

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

• signatures of peptide backbone conformation [27][28][29]: a random coil typically shows a negative band near 198 nm and a positive band near 218 nm; an α-helix exhibits characteristic minima at 208 nm and 222 nm and a maximum near 192 nm; β-sheet structures are often indicated by a single minimum between 210

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

• ] by flash column chromatography in 30% yield. The stereocontrolled formation of aryltetralin 13 could be attributed to an adoption of a pseudo-half-chair conformation 5a. Finally, the final step towards the total synthesis of (+)-aglacin B (2) was achieved by treatment with BF3·Et2O as the Lewis acid

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 and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• functionalization of the calix[4]arene skeleton blocked in cone conformation, as evidenced by the AX system (3.13 and 4.26 ppm) for the bridged CH2 protons. Spontaneous self-assembly Due to the amphiphilic nature, compound 3 could spontaneously self-assemble in aqueous medium. This was confirmed by dynamic light

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• details see Supporting Information File 1). The Db nucleobases were individually incorporated into the PNA model oligonucleotide and subjected to 50 ns unrestricted Desmond molecular dynamics. Pictures from the molecular dynamics simulations shown in Figure 7 represent the conformation of the PNA bases

• flexibility. Yet, for the Hoogsteen hydrogen bonding to occur using distal recognition monomers, the entirety of the flexible linker must enter the major groove being forced into a conformation that no longer is freely rotating. Additionally, these longer chains bring in potential issues of steric conflict

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

• , which has a stereogenic centre at C10, photocyclization afforded 10g in moderate yield and with excellent diastereoselectivity (76% yield, dr >20:1). This indicates that the reaction is controlled by the substrate conformation. To investigate the effects of the spirocyclic ring size on the

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• example of the furanose form stabilization was demonstrated wherein the introduction of a 3,6-O-(o-xylylene) bridge locked the mannopyranose in unfavorable conformation, thereby shifting the equilibrium toward the furanoside form (Figure 2D) [27]. Besides the approaches described in Figure 2

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• modulated the co-conformation of the rotaxane. However, the folded geometry of the axle restricts long-range movement of the macrocycle. Therefore, the authors later reported a photoswitchable rotaxane with an unfolded molecular thread, achieved by modifying the stopper groups and adjusting the linker chain

• photoisomerization of the stiff-stilbene allows the macrocycle to adopt a narrow-elongated conformation in the cis state and a wider geometry in the trans state. This light-induced conformational change was utilized to control the anion-templated formation of a pseudorotaxane. Specifically, the axle contains a

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

• conformation of the substrates, thereby modulating their reactivities. Density functional theory calculations show that 22 prefers to proceed its annulation through TS22b (ΔΔG‡ = 0) to afford 23 rather than that via TS22a (ΔΔG‡ = 1.5 kcal/mol). In contrast, annulation of 30 undergoes through the low barrier

• difference between TS30b (ΔΔG‡ = 0.3 kcal/mol) and TS30a (ΔΔG‡ = 0), resulting in the formation of 31 as a 1:1 mixture of regioisomers (Scheme 5c). In this work, to address unsatisfactory C4 stereochemistry in initial synthesis, the authors introduced a double bond to alter substrate conformation, enabling

• -diketones, the rigid lattice structure locks molecules into a specific conformation, limiting access to certain γ-hydrogens for abstraction and thus enhancing regioselectivity [42]. Enantiopure 87 was obtained by preparative chiral supercritical fluid chromatography (SFC) resolution of the racemate, while

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• previously for an anthracene-walled glycoluril tetramer host [43], G2W3 undergoes an end-to-end twist due to splaying of the aromatic sidewalls that results in an overall helical conformation that is chiral. The angle between the mean planes of the naphthalene rings amounts to 42.490°. Most relevant to the

• sequestration abilities of G2W3 is the conformation of the Ar–OMe groups. The splaying of the naphthalene sidewalls positions the Ar–OCH3 groups directly over the opposing naphthalene sidewall and vice versa. The OCH3 C-atom resides 3.4925 and 3.5563 Å above the mean plane of the opposing sidewall. Solvating

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• risk, as the strongly bound compounds affect membrane integrity, thus influencing the conformation of receptors and possibly causing side effects. As the outcome of pharmacokinetic characterization, lead-likeness was interpreted in Table 2 and Table 3, considering kinetic solubility, GI PAMPA

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• derivatives [41] the preferred conformation of (S)-2a can be proposed (Figure 2). In the case of the P conformer, a Newman projection along the C–N bond reveals that the bulkier substituent, the hydroxymethyl group (denoted as L), is close to a seven-membered ring, and is destabilized by steric repulsion with

• 293 K, the population of the P and M conformers were determined. CD and UV spectra of (a) tertiary amines (S)-2a–e and (b) quaternary ammonium salts (S)-2f,g and (R)-2h (2.0 × 10−4 M in CH3CN, 293 K). Schematic representation of the preferred conformation of (S)-2a. Four major conformers of (S)-3a

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• two triplets which are slightly downfield-shifted as compared to the aromatic protons in compound 6a. This observation reflects a rigid conformation of aromatic Hs after forming the 7-membered 1,4-diazepine ring in 8a. In addition, the 1H-1H COSY and HSQC analysis of compound 8a were conducted and the

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• the denitrogenation mechanism of 7,7‐diethoxy‐2,3‐diazabicyclo[2.2.1]hept‐2‐ene, showing that a stepwise C–N-bond cleavage is energetically favored using broken‐symmetry (BS)‐(U)CCSD/6‐31G(d) and suggested that an equatorial conformation of the diazinyl diradical leads to the formation of the inverted

• product. An alternative route via an axial conformation of diazinyl diradical for the inverted product was suggested using Born–Oppenheimer molecular dynamics [85]. Most recently, our group performed multireference calculations with CASPT2(8,8)/ANO-S-VDZP//CASSCF(8,8)/ANO-S-VDZP and non-adiabatic

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• -subsituents of ligand 183 are important to adjust the conformation of the ligand to provide suitable space for the smaller group. It is observed that the attachment of two n-butyl groups at the C5 position is beneficial for the reaction [65]. Although the ee of monobenzoate 185 was undetermined, azepinoindole

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• , tryptophan residues), as well as the overall structure of the protein. The peak intensity and shape can vary depending on pH, ionic strength, and protein conformation. However, under our conditions, the HSA oxidation was consistent, well‐defined, and served as a clear baseline reference. Subsequent to

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• chirality originating from the rigid conformation of molecules lacking symmetry, which do not fit into the aforementioned four categories, are termed inherent chirality. Notable examples include inherently chiral calix[4]arenes and saddle-shaped medium-sized cyclic compounds. Catalytic asymmetric synthesis

• reaction mechanisms and applications of the chiral products for selected examples. Review Helical chirality Helicenes are a group of rigid polycyclic aromatic compounds composed of ortho-fused aromatic (hetero)cyclic rings, with their helically twisted conformation enforced by steric hindrance between

• derivatizations. Based on experimental and computational studies, the origin of helical chirality in this method was elucidated. We proposed that the asymmetric Povarov reaction would generate a pair of diastereomeric tetrahydroquinoline derivatives displaying helical conformation, with a modest energetic barrier

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• strong as in the previous examples, a deeper analysis is usually needed to predict the photophysical properties of the azoheteroarenes. While the Z-isomer of 6-membered rings is always in a twisted conformation, it was discovered in the case of 5-membered rings that also a T-shaped conformation could be

• with bulky N-substitution suggest that the conformation is twisted, with reduced conjugation. Steric hindrance at the indoxyl nitrogen also provides higher thermal stability of the E-isomer, with mixtures of E and Z found at thermal equilibrium [77]. Heteroaromatic substitution in hemiindigo generates

• transition state E-inversion (Scheme 32A). The addition of ring strain between the stator and the rotor (Scheme 34, right) was found to affect the thermal half-life depending on the ring size [109]. Too small (n = 3) 108a and too large rings (n > 5) 108d–f force the E-isomer in a less stable conformation and

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• adapt a gauche-conformation (∠O3–C21–C22–O4 = 66.9(3)°, ∠O4–C23–C24–O5 = −77.3(2)°), and only the central ethylene glycol can be found in a trans-conformation (∠O5–C25–C26–O6 = −173.0(5)°). Probably induced by the linker, the commonly preferred perpendicular orientation of the naphthyl-units in the

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• /β = 8:1 and 7:1, respectively), the β,β-configured by-products were also formed, which was attributed to rapid anomerization of the lactol acceptor to the more reactive β-anomer during glycosylation. To minimize anomerization, the lactol acceptor was locked in a 4C1 conformation using a 4,6-O

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• defined by the two aromatic components of the sensor result in an essentially planar conformation at the free state, whereas binding to a naked barium cation results in a perpendicular arrangement between the benzo[a]imidazo[5,1,2-cd]indolizine and the 1,4-phenylene components, thus promoting a blue shift

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• the donor property but also to lower the energy of the LE state of the PTZ moiety. Notably, while PTZ adopts a non-planar conformation in the ground state, it undergoes planarization in the excited state [16][17]. This conformational change is expected to further enhance the stabilization effect

• . Although the PTZ unit adopts a bent structure in the ground state, it is known to undergo a structural transformation to a planar conformation upon excitation, as the planar geometry becomes more stable in the excited state. For instance, the planarization time constant of a phenyl-substituted

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• benzamidine derivatives as a novel pH-responsive molecular switch. Keywords: atropisomer; conformation; isomerization; molecular switch; organobase; Introduction pH-Responsive molecular motors and switches are a class of functional organic molecules capable of reversible structural and electronic changes

• behavior, allowing for both tunability and predictability. Among the various types of pH-sensitive molecular switches, those that rely on isomerism caused by the rotation of molecular bonds are attracting attention because they can apply the most basic property of molecular conformation to molecular

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• stable figure-eight conformation A to a metastable bathtub conformation B with a small energy difference of approximately 2 kcal mol–1 [21]. In this paper, we discuss the effect of the transformation of the carbonyl groups on the conformational change of the figure-eight structure. We thus intentionally

• ruled out. The structures of compounds 3, 4, and 5 were determined by X-ray diffraction analysis (Figure 2). Mono-olefin 3 and bis-olefin 5 adopt a bathtub-like chiral macrocyclic structure rather than figure-eight conformation. Both compounds crystallize as a racemic pair of enantiomers with P21/c and

• temperature. These are attributable to the mixture of conformers with the figure-eight conformation as minor and the bathtub conformation as major conformer with a ratio of ca. 1:7. The obtained temperature-dependent 1H NMR data were subjected to the van't Hoff plot, affording an enthalpy ΔH and an entropy ΔS