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

• intermolecular interactions in biological environments. This study clarifies the electronic origin of DFMO’s gauche effect and provides insight into how local electronic factors determine the structure of fluorinated amino acid derivatives. Keywords: conformational analysis; difluoromethylornithine; gauche

• intrinsic stereoelectronic preferences but also by intermolecular interactions within the ornithine decarboxylase active site. Therefore, the conformational behavior of DFMO arises from a delicate balance between the fluorine gauche effect and the intermolecular interactions that stabilize the ligand–enzyme

• changes in DFMO [11], a systematic evaluation of its zwitterionic and non-zwitterionic forms in the gas phase, aqueous solution, and biological environments is necessary to disentangle the respective contributions of intra- and intermolecular interactions to its conformation and biological activity. In

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

• states, intermolecular interactions enhance spin–orbit coupling and crystallinity suppresses nonradiative decay, thereby activating RTP. This work achieves an integrated “crystalline-state RTP–amorphous-state TADF” regulation within a single molecule. Keywords: imide; π–π stacking; room-temperature

• of both intra- and intermolecular non-radiative decay pathways [20][21][22]. Several strategies have been developed to enhance RTP in organic materials, such as incorporating functional groups with n→π* characteristics, such as carbonyl [23], sulfone [24], or sulfonamide groups [25], constructing

• intermolecular coupling to enhance SOC and suppress non-radiative decay channels, while TADF relies more on donor–acceptor decoupling and smaller ΔEST to lower the thermal activation barrier for RISC. Thus, a key challenge in the field is how to establish adjustable synergy between the molecular-scale

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

• geometry of the molecules and the intermolecular interactions in the crystals was carried out using the PLATON program [50] and the drawings of the molecules were performed using the MERCURY [51] programs. The non-hydrogen atoms were refined in anisotropic approximation. The hydrogen atoms were placed in

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• alkyl iodide 10 were subjected to nickel catalysis in the presence of zirconocene dichloride and zinc dust, intermolecular coupling occurred to afford ketone 12 in good yields. This reaction was applicable to substrates bearing β-alkoxy substituents, which are typically problematic under anionic

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

• -group elimination but through intermolecular hydride-transfer reactions as well. Therefore, the expected strategy to establish a chemical bond with a cycloheptatriene core is a reaction of a tropylium ion derivative with a nucleophile. Such reactions may involve either carbon [9][10][11] or heteroatom

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

• approaches focus mainly on intramolecular radical cyclizations [42][54][55][56][57][58][59][60][61][62][63], while intermolecular [1][64][65][66][67][68] N–N coupling remains a poorly studied area. In addition to the preparation of azo compounds [69][70], intermolecular N–N coupling reactions are of

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

• the OH group. The crystal packing of single crystals 4att, 4atc, 4acc, 4act, 4dct is ordered by intermolecular hydrogen bonds linking O–H groups and heteroatoms O/N of neighboring molecules (see Table S8 in Supporting Information File 1); N–H groups of the hexahydropyrimidine ring and a carbonyl

• hexahydrooxazolopyridone 5ctt is ordered by intermolecular hydrogen bonds of the NH2 group with the hydroxy and carbonyl functions of two other molecules (Figure 3b). The OH substituent of the piperidone ring is in the trans-configuration relative to O(4) atom. In the oxazolidine ring, the CH2NH2 group occupies a pseudo

• -equatorial position and is in the trans-position toward the Bu group. The single crystal structure of the bicycle 5ctc is ordered by intermolecular hydrogen bonds between the hydroxy group and the amino group as well as between the amino group and fluorine of the CF3 substituent of the neighboring molecule

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

• -sensitive hemiketal motif. The synthetic plan was to carve out the superfluous hydroxymethyl group in the late stage of the synthesis using a stereoretentive decarboxylative hydroxylation procedure [48]. A key step in the synthesis was an intermolecular Diels–Alder reaction between diene 97 and dienophile

• olefination to construct diene 97 for the Diels–Alder reaction. Dienophile 98 was constructed using a Horner–Wadsworth–Emmons (HWE) reaction between aldehyde 103 (2 steps from butenediol) and phosphonate 104 (1 step from commercially available materials). The intermolecular Diels–Alder reaction was achieved

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

• system with two molecules in the asymmetric unit. The bond distances in 3n C1=O1 is 1.229(4) Å and C2=S2 is 1.629(4) Å. For compound 4n, the observed C=O bond length is shorter than that of compound 3n (1.202(2) and 1.221(2) Å), respectively (Supporting Information File 1, Table S3). Intermolecular

• : a) 1H NMR spectra (600 MHz, DMSO-d6) with expansions, and b) 13C NMR spectra (151 MHz, DMSO-d6) with expansions. a) Molecular structure of 3n with crystallographic labeling (50% probability displacement). b) Perspective views of intermolecular hydrogen bonds (dotted lines) of 3n. (‘) symmetry

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• rearrangement. Finally, a White–Chen C–H oxidation [33][34][35] was employed to install the lactone ring, thereby completing the synthesis. The synthesis began with commercially available compound 19 and known compound 20 (Scheme 2). These were joined via an intermolecular aldol reaction to give adduct 21

• of 85 with iodine and BnOH enabled the intermolecular iodoetherification to yield ketal 86. A KF-promoted intramolecular alkylation of the cyclopentadiene moiety then delivered compound 87. To introduce the C4 hydroxy group and C1 functional handle for further elaboration, a nitroso-Diels–Alder

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

• is as follows: Starting from the chiral compound (S)-carvone, four simple transformations yield the enone intermediate 11. This intermediate undergoes an intermolecular [4 + 2] cycloaddition with diene 12, generating two sets of regioselective products in an approximate ratio of 1:1. The product with

• hemiacetalization to construct the oxa[3.2.1]-bridged ring system, thereby forming the D and E rings. Subsequently, the introduction of a tertiary hydroxy thiocarbonate at C11 afforded compound 38. Under thermal conditions, 38 underwent smooth introduction of an allyl fragment via intermolecular radical addition

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• structure, and saturation, can result in different membrane mechanics, hydration, thickness, intermolecular spacing, and non-covalent interactions with the rotaxane. For example, EYPC bilayer thickness increases linearly with cholesterol concentration and can induce the formation of nanodomains [16]. Such

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• ) derivatives are a valuable class of fused heteroaromatic compounds characterized by rigid planar π-conjugated backbones that provide narrow band gaps, high charge carrier mobility, and intermolecular π–π stacking interactions, making them particularly attractive for the design of organic materials. Indeed

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

• for precise control over their structural, dynamic, and functional properties. By harnessing light as a non-invasive stimulus with high spatial and temporal resolution, these photoswitches allow for the modulation of the rotaxanes’ intra- and intermolecular interactions, optoelectronic properties, and

• intermolecular interactions is a powerful strategy for designing sophisticated molecular systems that operate across multiple length scales, from nanoscale dynamics to macroscopic functions [1][2][3]. Light is particularly attractive compared to other stimuli due to its non-invasive nature, high spatial and

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• produce 11, which could be further converted to 12 and 13 for an intermolecular Mannich-type dimerization to form the C2–C3’ linkage [13]. Further oxidation state adjustment would give complanadines A, B, D, and E. Since their isolation, the complanadines, especially complanadine A, have attracted a

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• lactone 26. The Zhang group has extended the chiral metalloradical catalysis to cyclopropanation by the intermolecular reaction between styrenes and ketodiazoacetates [59]. Cyclopropanes were obtained in good yields with high relative and absolute stereocontrol. Properties, such as relatively high earth

• -trig cyclization and HAT furnished the enantioenriched products with up to 97:3 er. In addition to intramolecular radical reactions, intermolecular radical transformations have also been achieved using photoenzymatic catalysis, such as the addition of fluoroalkyl radicals to alkene substrates [36] and

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

• dual roles as solvent and nucleophile, the gold-catalyzed intermolecular Markovnikov addition of methanol to the gold-activated alkyne proceeded to afford dienol intermediate 4. The intermediate 4 subsequently underwent a regioselective 6-endo-trig cyclization, generating the naphthalene core 7 (Scheme

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• -catalyzed intermolecular Diels–Alder reaction of 106 with methacrolein 107 afforded the common intermediate 108 in high yield. Sequential Grignard reagent addition and acid-promoted ethoxy elimination provided the separable planar diene 109 (dr = 1:1), which underwent a Mn-catalyzed HAT hydrogenation to

• transformations of 121 generated bromodiene 122. Next, the metal–halogen exchange/intermolecular addition of 122 with aldehyde (+)-123 and in situ PtCl2-promoted hydrolysis and hydration gave tricyclic product 124. The BnMe3NOH-mediated intramolecular Michael/aldol cascade reaction of 124 constructed the C/D

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• investigated their solar thermal energy storage performance [46]. Key parameters governing the performance of azobenzene–RGO hybrid solar thermal fuels include hydrogen-bonding interactions, intermolecular distances between adjacent azobenzene groups, and electronic coupling effects. Conjugated azobenzene

• azobenzene polymer solar thermal fuels: (a) Photoisomerization and thermally induced reverse isomerization of diacetylene monomers. The inset depicts the crystal structure of diacetylene monomer (n = 6, X = N–H) with dashed lines indicating intermolecular hydrogen bonds. Figure 4a was used with permission of

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• rearrangements via the 1,2-silyl shift, enabled by the β-cation-stabilizing properties of silyl groups [19][20]. This phenomenon has been successfully employed in 1,3-difunctionalization events in both intermolecular [21] and intramolecular fashion [22] (Scheme 1B). Thus far such propargylsilane rearrangements

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

• with 99% ee. The TBS protection was crucial to prevent the potential racemization by intramolecular transesterification. Ester 79 was then prepared from 78 in eight steps. To complete the dimerization, fragments 80 and 81 were independently prepared from 79. An intermolecular Suzuki–Miyaura coupling

• the cyclohexanone ring into 120, and the resulting hydroxy group was protected to give ketone 121. The γ-lactam moiety of compound 122 was then constructed in subsequent 12 steps. SmI2-mediated intermolecular Reformatsky-type reaction with aldehyde 123 yielded compound 124. Finally, salinosporamide A

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• estimation of the yield of each product (Figure 2, panel B). It was found that many reactions involving alcohol- (e.g., C1–5, C8, C11 and C14) and indole- (e.g., C3, C12 and C15) containing co-substrates yielded intermolecular products, whilst those involving nitrile-containing co-substrates (C9 and 10) and

• the allylic ether C16 did not. It is remarkable that S(VI) electrophiles are tolerated. Eighteen substrate/co-substrate combinations gave, with at least one of the catalysts, an intermolecular product in >10% estimated yield (typically corresponding to >1 mg product). For all but one of these

• reactions, a product with molecular weight consistent with O–H insertion into water was also observed. For these 18 substrate/co-substrate combinations, the reaction with the highest estimated yield was selected for mass-directed purification (Table 2). In total, 23 intermolecular reaction products were

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• an important class of compounds with significant biological activities. Spirocyclic derivatives are present in a variety of natural products. We describe here the formation of spirooxindoles using an intermolecular nitrone cycloaddition reaction. The nitrone dipole was prepared in situ by cyclisation

• possibility to access the core of this ring system with the nitrone intermediate shown in Scheme 1A. As a model study, we describe here efforts towards an intermolecular variant with the oxindole shown in Scheme 1B; in this case a leaving group X will be displaced by the oxime to give an intermediate nitrone

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

• tautomerism is an intermolecular process that depends not only on the choice of aryl rings and substituents but also on concentration, solvent polarity, and the presence of proton sources [5][15]. In conclusion, the choice of aryl rings, substituents, and substitution position are all crucial to determine the

• concentration of the photoswitch in solution: when MeOH or water are present, the lifetimes drop significantly, and particularly at pH 4, as consequence of more favourable intermolecular proton transfer. Calculations show that water molecules bridging between two Z-isomers favour the formation of hydrazone and

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• ) [103]. CA4-Man3-NPs achieve efficient targeted drug delivery through a unique self-assembly mechanism. This system leverages the unique polymeric characteristics of CA4, which reduces the critical aggregation concentration and enhance intermolecular orderliness to form structurally stable nanocarriers