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

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• data, compound 3aa crystallizes in the centrosymmetric spatial group of the monoclinic system. The molecule has a tweezer-like conformation due to π–π interactions between the electron-donating tolyl and the electron-acceptor fragment NC‒C=C‒S. The heterocyclic fragment in the molecule is non-planar

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

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• accordance with coupling constants and resulting dihedral angles. Keywords: conformational restraints; dihedral angle NMR; half-chair conformation; modified amino acids; pipecolic acid; stereoselective hydrogenation; Suzuki–Miyaura cross-coupling; Introduction Non-proteinogenic amino acids play an

• important role as building blocks for peptide synthesis [1][2][3][4][5], as organocatalysts [6][7][8][9][10] and as enzyme inhibitors [4][11][12][13]. The incorporation of such amino acids into peptides can, for example, influence peptide conformation, the binding affinity to receptors [14], as well as

• broad doublets instead of double-doublets (Figure 2a,b). The lack of a second coupling constant indicates a conformation in between a chair and a boat with a dihedral angle ϕ near 90°, which is necessary for a coupling constant to be around 0 Hz. Half-chair or twist-boat conformations are well known for

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• projected benzyl groups. For the 1/NaBArF24 complex, the repeating unit shows that both phenylalanine HIMs exhibit the same conformation (e.g., I) where all three benzyl groups are oriented toward the interior of the macrocycle (Supporting Information File 1, Figure S9). From the single crystal data set, we

• -crystal. Li+ complex 2 (Figure 8) represents the complex consisting of HIM in two different molecular conformations I and II, whereas Li+ complex 3 (Figure S19 in Supporting Information File 1) represents a complex consisting of both macrocycles in the same molecular conformation (e.g., I and I

• ). Similarly, Na+ complex 4 (Figure S20, Supporting Information File 1) represents the complex consisting of HIM in two different molecular conformations I and II, whereas the Na+ complex 5 (Figure S21, Supporting Information File 1) represents a complex consisting of both HIM in same molecular conformation, I

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• triphenylmethyl radical [38][39]. In contrast to the Gomberg radical, the perchlorination prevents dimerization through the para-position. Moreover, the chlorine substituents in the ortho-positions twist the phenyl rings into a propeller conformation and out of the sp2-hybridization plane of the central methine

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

• excited state. This results in a consistently planar conformation for donor b, while donor a can exhibit either a planar or bent conformation, depending on the nature of the substituent, as previously mentioned. This duality between planar and bent shapes is significant, as it contributes to the aromatic

• CT stabilization of the first excited state of the molecule [34]. This observation is further supported by the orthogonal D–A conformation calculated using DFT, which indicates a decoupled interaction between the HOMO and the LUMO (Figure 2). Moreover, compound 5e is the only member of the family in