Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• and allomaltol derivatives have the wide variety of biological activity [12][13][14][15][16]. This means that designing such hybrid products can significantly alter the pharmacological properties. Results and Discussion The starting compounds 1 were prepared from allomaltol employing a previously

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• research communities. This has led to the creation of hybrid systems – improvised combinations of commercial ball mills with transparent jars (e.g., PMMA, glass, quartz, or epoxy resin) and off-the-shelf LED lamps or strips. However, a standardized apparatus for photomechanochemistry is not available yet

Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane

• Zahra Noori,
• Miquel Solà,
• Clara Viñas,
• Francesc Teixidor and
• Jordi Poater

Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29

• Barcelona, Spain 10.3762/bjoc.21.29 Abstract A new series of o-carborane-fused pyrazoles has been recently successfully synthesized. This fusion was expected to create a hybrid 3D/2D aromatic system, combining the 3D aromaticity of o-carborane with the 2D aromaticity of pyrazole. However, while the boron

• expected to create a hybrid 3D/2D aromatic system, combining the 3D aromaticity of o-carborane with the 2D aromaticity of pyrazole. Notably for the case of pyrazole or pyrazoline, the N–N bond length is diagnostic, being approximately 0.1 Å longer when the molecule lacks aromaticity. In contrast, o

• calculations were performed with the Gaussian 16 package [64] by means of the B3LYP [65][66][67] hybrid density functional and the 6-311++G(d,p) basis set [68]. The geometry optimizations were carried out without symmetry constraints (Table S2 in Supporting Information File 1). Analytical Hessians were

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• ://www.ccdc.cam.ac.uk/data_request/cif. Computational methods Quantum chemical calculations were performed using the Gaussian 09 software package [34] with hybrid functional PBE0 [35][36] and 6-311+G (d,p) basis set. Solvent effects were modeled by using polarizable continuum model (PCM) [37] within the integral

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• previously reported study investigating the biosynthesis of tenellin from Beauveria bassiana CBS110.25 [13], it was established that tenellin and a vast array of related metabolites could be synthesized through a cascade involving hybrid highly reducing polyketide synthase–non-ribosomal peptide synthetase

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• demonstrating the highest potential among the tested compounds against acetylcholinesterase. Furthermore, Pachón-Angona et al. [35] synthesized hybrid molecules using the Ugi reaction (Scheme 3), with antioxidant compounds as starting substrates, pursuing the aim of developing more powerful antioxidants. The

• reaction to produce pyrazine-based MTDLs. Synthesis of BCPOs employing a Knoevenagel-based multicomponent reaction and the best candidate synthesized. Hantzsch multicomponent reaction for the synthesis of DHPs as novel MTDLs. Chromone–donepezil hybrid MTDLs obtained via the Passerini reaction. Replacement

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• highly bioactive compounds that can be converted into drug candidates in a fast and efficient manner containing these moieties is the molecular hybridization [8][9][10]. It consists of covalently joining of two or more pharmacophoric fragments to provide new hybrid compounds with improved efficacy and

• previously described strategies involved the use of higher-order multicomponent reactions (HO-MCRs). As part of our ongoing research program towards the synthesis of novel hybrid compounds based on the 1,5-disubstituted tetrazole moiety [23][24][25][26][27], we developed a synthetic strategy for the

• synthesis of a novel bis-heterocyclic hybrid, 1,5-disubstituted-tetrazole-indoles. The compounds were achieved through a high-order multicomponent reaction consisting of two sequential processes: an Ugi-azide reaction and a further Pd/Cu-catalyzed heteroannulation (Scheme 1d). Results and Discussion Our

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• previously found that the reaction between 3,5-di-tert-butyl-6-methoxymethylcatechol and different functionalized thiols occurs via an acid-catalyzed mechanism and leads to corresponding thioethers with methylene linker [53][54]. Hybrid structures of this type are of particular interest from the point of

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• biological activity was determined for these compounds. Pestauvicomorpholine A (34) is an exceptional hybrid metabolite with fusion of a polyketide-derived resorcylic lactone and the steroid dihydroergosterol, which was isolated from the fungus Pestalotiopsis uvicola [174]. Its structure was determined by

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• truxenes with freshly distilled pyrrole using trifluoroacetic acid (TFA) as an acidic catalyst afforded the anticipated DPM-appended truxene derivatives (14, 16 and 18) in good yields (60–80%). All the newly prepared DPM-linked truxene-hybrid molecules as well as the intermediate acetylated truxene

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• [31]. Range-separated hybrid GGA (RSH-GGA) functional, including dispersive interaction with 6-31G* as the polarization basis set (ωB97X-D/6-31G* method), was used for energy and geometry optimization [32]. Bioactivity Cytotoxicity and tyrosinase assays were carried out according to the procedures

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• , experimental procedures, and characterization data. Supporting Information File 30: Copies of NMR spectra. Funding This work was partially supported by a Grant-in-Aid for Scientific Research on Innovative Areas “Hybrid Catalysis for Enabling Molecular Synthesis on Demand” (JP17H06447) and a Grant-in-Aid for

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• molecules. Tautomerism of indazole. DFT-calculated deprotonation of 6 with Cs2CO3 in implicit THF with the temperature of the calculation set to 90 °C to simulate the dioxane conditions (top) and energy differences of four enolate resonance structures of 6 calculated as discrete structures. The hybrid is

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• used as acid components in tandem combinations of various multicomponent processes such as Ugi and Ugi, azido-Ugi and Ugi, Ugi and Passerini, Groebke–Blackburn–Bienaymé and Ugi, etc. [15][17][37][38]. The creation of hybrid molecules by using primary and post-modified Ugi products in combination with

• bisamides based on the same aldehydes and amines may also demonstrate biological activity. In view of these facts, we decided to develop a new approach for the synthesis of hybrid molecules containing substituted heterocyclic and peptidomimetic moieties. The first stage of this approach was the preparation

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• structure B, which is further destabilized by the neighbouring ketone. A similar resonance hybrid will be formed for molecules substituted in the 4-position, like 6b, explaining the selectivity towards p-quinones. Abstraction of a proton rearomatizes the molecule before another cation is formed in the

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• hybrid syntheses of cotylenol (1) and brassicicenes [19]. The key oxidative allylic rearrangement was conducted enzymatically, while the skeletal rearrangement originally mediated by P450 enzymes in the biosynthetic pathway was achieved through chemical transformation. Hence, this strategy can be

• tolerance through enzyme mutagenesis should allow more precise control over scaffold-constructing reactions. As with the related natural products, hybrid sorbicillinoids were also known to be biosynthesized through Diels–Alder reactions between diene 34 and non-sorbicillinoid-derived dienophiles [29

• ]. Gulder and co-workers achieved the total synthesis of hybrid sorbicillinoids using the established chemo-enzymatic synthetic process, in addition to the synthesis of homodimers (Scheme 4B). Upon treatment of the extract of the enzymatic reaction mixture containing (S)-34 with dienophile 39, sorbicatechol

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• relaxed substrate specificity for all maturases in the aer BGC: All hybrid precursors were extensively modified with dehydrations, C-methylation, N-methylations, and epimerisations comparable to the AerA precursor [112][113]. PbtM1 from the thiopeptide GE2270 BGC is another example of a side chain amide-N

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• partition coefficient logarithm (log P), H-bond acceptor/donor count (HAcc/HDon), fraction of sp3-hybrid carbon atoms (F(sp3)), and rotatable bond count (RotB) are shown in Figure 5. It is apparent that the GBB chemical space contains many drug-like (69,043,101 molecules, 25%) and “beyond-Ro5” compounds (75

• count; F(sp3) – fraction of sp3-hybrid carbon atoms; RotB – rotatable bond count); compounds complying with specific Lipinski/Veber rules (MW ≤ 500, log P ≤ 5, HDon ≤ 5, HAcc ≤ 10, RotB ≤ 10 [38][41]) as well as compounds with F(sp3) > 0.5 are highlighted in blue, the rest of the compounds are shown in

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• yields (up to 97%) and high enantioselectivities (up to 98.5% ee) under mild reaction conditions. In addition, this protocol was further expanded to synthesize highly enantioenriched hybrid molecules bearing biologically relevant heterocycles. Keywords: α,β-unsaturated ketones; iminium catalysis

• (Scheme 2) were obtained in good to excellent yields (71–97%) and enantioselectivities (83.5–98% ee). Molecules containing two or more biologically relevant heterocycle motifs are receiving attention in drug discovery research [31][32][33]. The enantioselective synthesis of such hybrid molecules is

• such compounds might be endowed with potent biological activities. Under the disclosed optimized reaction conditions, the reaction between pyrazolin-5-one (2a) and indole-derived α,β-unsaturated ketone 1m was performed. The resulting hybrid molecule 3ma was isolated in 96% yield and 90% ee (Scheme 3

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• -deficient alkynes [59][60][61][62][63]. The in situ generated cyclic intermediate C has a resonance hybrid C’. Then, the further nucleophilic addition of the electron-rich enamino unit to 5-(alkylimino)cyclopenta-1,3-diene intermediate C gave intermediate D. At last, the coupling of the iminium cation with

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• experiments in solution, a one-pot cleavage from the resin combined with the CuAAC reaction to the triazole–pyrazole hybrid was conducted exemplarily and gave the target product 21gd in 30% yield. The solid-phase reaction route allows for roughly equally high overall yields compared to the solution synthesis

• ORTEP diagrams of triazole products 21sd and 21vg with the thermal ellipsoids shown at 50% probability. NaAsc = sodium ascorbate. One-pot synthesis of triazole–pyrazole hybrid 21gd. aOne-pot setup yielded 21gd with unknown impurities; bwith an additional evaporation step after the triazene cleavage, a

• quantitative yield of the target product 21gd was achieved. Solid-phase synthesis of azidopyrazole 19g and triazole–pyrazole hybrid 21gd by immobilization of aminopyrazole 14b on benzylamine-substituted Merrifield resin 22, NH-functionalization and cleavage. Reaction conditions: a) BF3∙Et2O, isoamyl nitrite

Synthesis and physical properties of tunable aryl alkyl ionic liquids based on 1-aryl-4,5-dimethylimidazolium cations

• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2024, 20, 1278–1285, doi:10.3762/bjoc.20.110

• [PhImC4H9]+, the unsubstituted 4,5-dimethyl-1-phenyl cation of TAAIL 37 and the cations of TAAILs 40 (4-CH3) and 49 (4-CF3). The structures of the cations were optimized with Gaussian 16 [56], using the hybrid functional Becke3LYP [57][58][59][60] with the split valence triple-ζ basis set 6-311++G(d,p) [61

Synthesis of indano[60]fullerene thioketone and its application in organic solar cells

• Yong-Chang Zhai,
• Shimon Oiwa,
• Shinobu Aoyagi,
• Shohei Ohno,
• Tsubasa Mikie,
• Jun-Zhuo Wang,
• Hirofumi Amada,
• Koki Yamanaka,
• Kazuhira Miwa,
• Naoyuki Imai,
• Takeshi Igarashi,
• Itaru Osaka and
• Yutaka Matsuo

Beilstein J. Org. Chem. 2024, 20, 1270–1277, doi:10.3762/bjoc.20.109

• differences between t-Bu-FIDO and t-Bu-FIDS, the density functional theory (DFT) method was employed using the B3LYP hybrid functional. The 6-31G* basis set was used for the geometry optimization and frequency calculation. The thiocarbonyl group in FIDS was found to have an out of plane bending vibration