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

• , illisimonin A was obtained only as a minor product. When O2 was replaced with the nitroaromatic compound 66 [38], the diastereoselectivity was reversed, thereby providing illisimonin A in 57% yield as a single diastereomer. The authors proposed that a hydrogen bond between the nitro group of 66 and the C8

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

• single hydrogen bond [29][30]. In efforts toward improving pyrimidine recognition, several groups have explored PNA nucleobase monomers using extended nucleobases to utilize maximum hydrogen bonding interactions across the Hoogsteen face of the Watson–Crick base pair [13][15]. Notable examples of the PNA

• nucleobases that showed enhanced triplex stability through cooperative effects compared to the control thymine base. In a follow up study, the pendant amide was removed from the Io core to determine the importance of the third hydrogen bond. To our surprise, these second-generation Io derivatives retained

• strong binding so long as the nucleobase lacked significant hydrophobicity [36]. This led to the hypothesis that quite possibly the third hydrogen-bond to the U base may not have been as important as originally believed. Given this result, we set out to design new nucleobases that reach across the entire

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

• five-membered ring due to the formation of an intramolecular hydrogen bond (Figure 2A). It has been shown that furanoside is preferentially formed in nonpolar solvents such as toluene. This form was successfully fixed and purified as benzoate derivative. Bulky substituents can also stabilize the

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

• has been largely supplanted by greener methods employing less-toxic reagents. Using alternative methods, radicals can be generated by hydrogen atom transfer (HAT), resulting in the homolytic cleavage of a carbon–hydrogen bond. Other approaches for radical generation in modern radical transformations

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• amine in terminal position. Based on this, our strategy was to design new inhibitors with introduction, in their terminal part, of an acid group which could perform an extra hydrogen bond or a salt bridge with lysine 241 and therefore could be specific to CLK3. Towards this goal we started from our

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

• File 1, Figures S1–S3). Based on their calculated physicochemical properties, all compounds satisfied Lipinski’s Rule of Five suggested by Wager et al. [34] (molecular weight < 500 Da, logP < 5, number of hydrogen-bond donors < 5, number of hydrogen-bond acceptors < 10) [35], and the topological polar

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• precipitation from non-polar solvents such as hexane and toluene did not lead to a complete separation of quinoxalinones 9 and Ph3PO. We attribute this to the ability of Ph3PO to form a strong hydrogen bond between the phosphoryl oxygen and a proton from the donor group of the second molecule [56][57][58], in

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

• pronounced red-shift of the E-isomer was observed for the pyrrole derivative 66 [81], showing that the hydrogen bond between pyrrole and carbonyl also plays a role (Scheme 21, left). The band separation also provides almost quantitative PSS in both directions. The imidazole derivative 67 (Scheme 21, right

• ) can interchange between tautomers to make a chalcogen bond with sulphur in the Z-isomer and a hydrogen bond in the E-isomer [64]. Extension of the conjugation with additional electron-rich arenes enables isomerisation with wavelengths up to >700 nm, with high PSS and high quantum yield. Electron-poor

• heterocycles generally possess strongly overlapped spectra with low PSS and low resistance to fatigue [64][82]. The hydrogen bond was also recently used to generate photobases [83]. Hemithioindigos with fully substituted double bonds have also been reported: more rigid stiff stilbene moieties have been

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

• well known for their strong 1,2-trans-stereodirecting effect [44][90][91]. On the other hand, the use of N-Troc and N-Fmoc as protecting groups in GlcN-based lactol acceptors offers the advantage of stabilizing the α-configuration via an intramolecular hydrogen bond between the axial anomeric hydroxy

• -carbamate-protected GlcN derivatives, such as the 2N-Troc-protected lactol 176 or the 2N-Fmoc-protected lactol 178, in which the α-configuration is reinforced by a hydrogen bond between the anomeric OH group and the N-carbamate moiety (Scheme 14). The α-anomeric configuration on the side of the imidate

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• a = 16.1017(4) Å, b = 7.7608(2) Å, c = 28.8344(8) Å, and β = 93.3680(10)°. Additionally, the presence of lattice water greatly influenced the molecular packing. The hydrogen bond (H–O–H) lengths in this lattice water ranged from 1.923 to 2.204 Å (Figure 2b). The pyruvylated galactose 6 was utilized

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• Chemical Technology of Russia, Miusskaya sq. 9, Moscow, 125047, Russia National Research University Higher School of Economics, Myasnitskaya St. 20, Moscow, 101000, Russia 10.3762/bjoc.21.130 Abstract Reducing agents with phosphorus–hydrogen bond, such as sodium hypophosphite, phosphite, and

• of the most actively applied reductants with phosphorus-hydrogen bond in industry, for example, in production of polymers [1], pharmaceuticals [2], electroless plating [3], metal corrosion prevention [4] and even food preservation [5]. NaH2PO2 is a non-toxic (LD50 7640 mg/kg – rat) (SDS Thermo Fisher

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• reaction coordinate, and particularly, at the transition state region. This results from the formation of a stabilizing, intramolecular CH3–OH···O=CH2 hydrogen bond at the initial stages of the process which brings together both reactants, significantly enhancing the orbital interactions (mainly HOMO–LUMO

Azobenzene protonation as a tool for temperature sensing

• Antti Siiskonen,
• Sami Vesamäki and
• Arri Priimagi

Beilstein J. Org. Chem. 2025, 21, 1528–1534, doi:10.3762/bjoc.21.115

• complexes between 1–3 and MSA (X-MSA and X-(MSA)2, X = 1, 2 or 3). The geometry-optimized structure of 3H+MSA−MSA is shown in Figure 3. In this structure, the second MSA molecule does not bind directly to the azo group but forms a hydrogen bond with the mesylate anion, and one of its oxygen atoms interacts

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

• involved in the formation of a weak intermolecular hydrogen bond of the C‒H···N≡C type with distances H(3)···N(3) 2.53(3) Å, C(3)···N(3) 3.436(4) Å and angle C(3)H(3)N(3) 157(2)° (symmetry transformation [1−x, 1−y, 1−z]). Conclusion Thus, we found that thioamides of acrylic acid easily interact with

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

• tetrahedral value which results in a large ring strain of 25.5 kcal/mol, comparable to oxirane (27.3 kcal/mol) and much greater than tetrahydrofuran (5.6 kcal/mol) [4]. Moreover, the strained C–O–C bond angle effectively exposes the oxygen lone pairs, making oxetane a strong hydrogen-bond acceptor and Lewis

• base [5]. In fact, its hydrogen-bond-accepting ability is even stronger than that of the other 3-, 5- and 6-membered cyclic ethers, as well as the carbonyls of aldehydes, ketones, esters and carbonates [6][7][8]. The only better carbonyl-based hydrogen-bond acceptors are amides, carbamates and ureas [9

• (Figure 2) [10][11][12]. As for the analogy to carbonyls, oxetanes display comparable polarity, spatial arrangement of the oxygen lone pairs and hydrogen-bond-accepting ability. In addition, they possess one major advantage and that is greater metabolic stability: while carbonyl groups are susceptible to

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• by hydrogen-bond interactions and oriented in alternating head-to-head and tail-to-tail modes comprising a continuous channel filled by an alternating [K(OH2)6]+ and [AuBr4]− polyionic chain (Figure 1). The authors further demonstrated that the process is selective for gold by determining, using ICP

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• . Similarly, Rajendran and Rajan (2024) utilized catalytic DABCO to perform the esterification of cinnamamide 99, where DABCO acted as a hydrogen-bond acceptor for phenol (Scheme 43B) [82]. Yuan-Yong and co-workers (2022) reported a DABCO/Fe3O4-catalyzed N-methyl amidation of cinnamic acid 122 via cooperation

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

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• attention due to their modular hydrogen bond donor/acceptor profile that can be tuned by varying the nitrogen position and the degree of unsaturation as well as by fusion with other rings [3]. Benzodiazepines, which contain a seven-membered diazepine core fused to a benzene ring, are recognized as

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• single-electron transfer with substrate 72 to form radical intermediate Int-70, completing the DPZ catalytic cycle. Intermediate Int-70 adds to substrate 73 to form radical intermediate Int-71, which further adds to hydrogen-bond-activated substrate 74 to form hydrogen-bonded complex Int-72. When Na3PO4

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• a dihedral angle of 49.86(10) 86.22(11)° with the phenyl rings C6–C11 and C18–C23, respectively. The angle between both phenyl rings is 70.76(11)°. The stereochemistry around the double bond is Z, allowing an intramolecular N–H···O hydrogen bond between one of the carbonyl oxygen atoms and the amino

• enhance its interaction with iNOS via the optimization of the hydrogen bond with Cys200. These results highlight the potential of compound 5e as a lead compound for further development in targeting iNOS-related pathologies. Experimental results have confirmed that compound 5e is a promising candidate for

• ellipsoids at the 30% probability level. The intramolecular hydrogen bond is shown as red dashed line. The bioavailability radar of studied compounds 5a–e. The interactions of potential drugs 5a–c in the active site of enzyme iNOS. The interactions of potential drugs 5d and 5e and control drug (DEX) in the

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• fluorophore derivatives bind the Pepper aptamer with affinities in the low nanomolar range [12]. Crystal structure analyses revealed that in the ligand binding pocket, a characteristic hydrogen bond is formed between the hydroxy group of the N-hydroxyethyl substituent of HBC and the N7 of G41 [12][13]. We

• -dimensional structure of the Pepper binding site with a bound HBC derivative (pdb code 7EOM). The hydrogen bond between N7 of guanine in position 41 (G41) and the hydroxy group of HBC is highlighted as gray dashed line [12]; d) concept for covalent attachment of HBC fluorophores to the N7 atom of G41 of the

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

• intramolecular hydrogen bond between the NH-unit and the carbonyl group. The presented results indicate that the reaction of the aliphatic amine doesn’t lead to recyclization of the studied heterocyclic system. Further, we hypothesized that synthesis of the enamine 4a can be realized in one-pot variant without

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• bimanes studied: a) Cl2B (B), representing 90% of the disordered asymmetric unit, b) Me2B, not disordered with dotted line representing an intramolecular hydrogen bond, and c) Me4B showing the majority occupied (55%) N–N moiety. View of the molecular structure in the crystal of a) symmetry generated by

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

• obtained as a single stereoisomer and in quantitative yield after 80 h of irradiation. The role of 2.2 is to create a close-packed environment via hydrogen-bond interactions where the [2 + 2] photodimerization can occur stereoselectively. Next, the authors evaluated the possibility of using the template