Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• decarboxylase and as a therapeutic agent against African trypanosomiasis. Beyond its pharmacological importance, DFMO provides a valuable model for examining how fluorine substitution governs molecular conformation. A comprehensive quantum-chemical study was performed to elucidate the origins of DFMO’s

• interactions (typically σCH → σ*CF) that stabilize conformations in which the C–F bonds adopt a gauche orientation relative to polar bonds, such as C–N or C–O [8][9][10]. In DFMO, the difluoromethyl group is directly connected to the ornithine backbone, and its conformation is expected to be shaped not only by

• complex. Elucidating this interplay is essential for rationalizing DFMO’s inhibitory potency and may also offer broader insight into how fluorinated substituents control molecular conformation in biologically relevant environments. Although the biological milieu is known to induce only minor structural

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

• reasonably inferred that, in the amorphous state, intermolecular π–π stacking interactions are significantly suppressed. This suppression of π–π interactions, along with a more disordered molecular conformation and microenvironment, makes it difficult to establish effective rigid constraints necessary for

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

• conformation is less polar and more rigid in nature, and thus reducing the energetic penalty that is typically associated with this process. The possible impacts of such IMHBs on membrane permeability are well recognized [16][17]. Therefore, it appeared reasonable to speculate that a possible IMHB of 1 could

• isotope effect experiments, this suggests that under physiological conditions, a significant fraction of 1 will be able to adapt a conformation with an IMHB – the species that is most amenable to cross biomembranes. It should be mentioned that there could also be an IMHB present in the protonated form

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

• than the 80–100° range typically reported for the most stable conformation of binaphthyl groups [24]. In contrast, the dihedral angles between the binaphthyl unit and the coordination plane were 54° and 52°, respectively. The UV–vis spectral simulation based on electronic transition obtained from time

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

• cyclopropane ring is probably a consequence of the formation of a sterically hindered carbanion II in a conformation with an anti-periplanar position of the bulky substituents – bromine and a trichloromethyl group (Scheme 6). Due to the steric reasons, the anion in this conformation is selectively protonated

• bromine. The cyclization step from this conformation leads to trans-cyclopropanes. X-ray diffraction analysis data for compounds 2, 3, 9a, and 9b convincingly confirm the accepted structures, the position of cyclopropane protons, and the relative configurations of asymmetric atoms (Figures 2–5). It should

• enatiomeric pair S,R,S/R,S,R is realized, and in crystal 9b – S,R,R/R,S,S. The main geometric parameters (bond lengths and valence angles) and the conformation of independent molecules in crystals of 2, 3, 9a and 9b coincide within the experimental errors, so Figures 2–5 show the geometry of one of the

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

• 81 was prepared via a Polonovski–Polish reaction and isomerization, which, when adopting the proper conformation, spontaneously underwent an intramolecular [4 + 2] cycloaddition to construct the unsaturated bridged ring of (±)-keramaphidin B in a single transformation. Subsequently, the iminium ion

• oxygen atoms from the substrate and the metal catalyst, which fixed the conformation of the polycyclic scaffold. As a result, the top face is sterically less favored, thereby hydrogen approaches from the opposite face. The subsequent addition of another two equivalents of hydrogen also supported this

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

• hydrazonocycloheptatriene 10k. Notably, dihydroindazoles 8 and 9 are similar to that previously formed from 1 [17]. In this investigation the most questionable is the attack onto the i-position. In our previous studies we have substantially investigated the geometry of anion 2 in the most stable conformation, which has a

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

• (Figure 2 and Figure 3), the piperidone ring has a half-chair conformation in which the pseudo-equatorially located trifluoromethyl group is a conformational anchor. The five atoms of the six-membered piperidone ring are coplanar, and the trifluoromethyl-substituted carbon atom С(8) is significantly

• deviated by more than 0.5 Å above or below the ring plane. Accordingly, the adjacent hydroxy substituent has a pseudo-axial position. The hexahydropyrimidine ring in bicycles 4аcc, 4аct, 4аtt, 4аtc, 4dct has a chair conformation, and the oxazolidine ring in heterocycles 5ctc, 5ctt has an envelope

• conformation, with a deviation of the oxygen atoms O(1) by 0.5 Å for 5ctc and nitrogen atoms N(1) by 0.4 Å for 5ctt. In trans-junction, bicycles 4att, 4atc (Figure 2c,d) have a flattened fixed skeleton with a dihedral angle of 24.8–27.3° (see Table S9, in Supporting Information File 1), in which the

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

• (Scheme 1, Compound A, X = -OCH3), the nucleophilic addition of the tosylate to carbenium ion is found to be syn. An anti-addition was also studied but it is found to be an unfavourable conformation for subsequent aryl migration [34]. On account of this, the current study focuses on the syn-addition

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