Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• donor, through a late-stage glycosylation. The aglycon 2 can be derived from the Δ14 olefin intermediate 3 via Mukaiyama hydration and several functional group transformations. In turn, 3 would be generated from the key C14α-hydroxylated intermediate 4 via an elimination process. For the synthesis of 4

• hand, we first tried the synthesis of rhodexin A through direct glycosylation of 2 by the ʟ-rhamnose donor 2,3,4-tri-O-benzoyl-α-ʟ-rhamnopyranosyl trichloroacetimidate (14). However, the selective glycosylation at the C3-hydroxy group of 2 was a formidable challenge since competitive glycosylations of

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

• -bonded carbon atom. Given that 3n and 4n contain donor–acceptor (DA)-type groups separated by a π-bond, the study of their photophysical properties has become particularly interesting. This structural arrangement often facilitates an internal charge transfer (ICT) process, which is common for such

• , thus hindering an ICT process (see Supporting Information File 1, Scheme S2). The molecular structure of compounds 3n and 4n can be separated in three blocks: a donor region, a π bridge and an acceptor region (Figure 9) common to molecules with intramolecular charge transfer (ICT) states. M06-2X/def2

• -TZVPP single point calculations in CPCM water of compounds 3n and 4n in protonated, deprotonated, and neutral forms showed that there is a degree of charge transfer between a HOMO–LUMO excitation in their neutral and deprotonated forms [98]. Protonation of the nitrogen atom in the donor region shifts

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

• visible region, and improved morphological stability [4][5][6]. Recent reports have shown that the development of alkyl-supported TT-based semiconductors has led to high-performance, air-stable OFETs [7], while integration of TT frameworks into donor–acceptor architectures has enabled the development of

Ex-situ generation of gaseous nitriles in two-chamber glassware for facile haloacetimidate synthesis

• Nikolai B. Akselvoll,
• Jonas T. Larsen and
• Christian M. Pedersen

Beilstein J. Org. Chem. 2025, 21, 2465–2469, doi:10.3762/bjoc.21.188

• donor; haloacetimidates; haloacetonitrile; two-chamber reactor; Introduction Trifluoroacetonitrile is an electrophilic reagent that has seen a variety of uses, mostly for incorporating trifluoromethyl groups into organic compounds [1]. As an example it has been successfully utilized for the synthesis

• trifluoroacetonitrile [24]. Schmidt published the first synthesis of glycosyl trifluoroacetimidates and concluded that their glycosyl-donor properties were similar to the trichloroacetimidates, but more difficult to prepare and purify [24]. In contrast to these observations, Nakajima et al. reported the

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

• content, compared to pure acetonitrile. Photocyclization of the dithienylethene with UV light quenches the fluorescence of the TPE due to Förster resonance energy transfer (FRET) between the TPE (donor) and the closed dithienylethene (acceptor). Irradiation with visible light triggers the cycloreversion

• along the axle in response to pH changes, moving farther from the spiropyran upon the addition of acid. In the spiropyran form, no FRET occurs between the tetraphenylethylene fluorophore on the macrocycle (donor) and the spiropyran unit, regardless of their relative positions. However, upon

• photoisomerization to the merocyanine (open) form, FRET is activated – even when the macrocycle is relatively distant from the merocyanine – and becomes more pronounced as the donor approaches the acceptor. Moreover, this rotaxane exhibited tunable photoluminescence properties in response to solvent polarity, pH

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

• -phosphatidylcholine (16 mg) and cholesterol (4 mg) in a solvent mixture of chloroform, hexane and dodecane (5/70/25 vol %). Each well of the PAMPA donor plate (MAIPNTR, PVDF membrane, Merck KGaA, Darmstadt, Germany) was coated with 5 μL lipid solution. Thereafter the donor plate was fitted into the acceptor plate

• (MSSACCEPTOR, Merck KGaA, Darmstadt, Germany) already containing 300 μL PBS (pH 7.4) solutions with 1% DMSO. Finally, 150 μL of the initial solutions was pipetted into the donor plate, the plate sandwich was covered with a wet paper tissue and with a plate lid to avoid evaporation, and the system was incubated

• at 37 °C for 4 hours. Then samples were taken from the donor and acceptor wells and analyzed along with the initial solutions by HPLC. Effective permeability and membrane retention were calculated with Equation 1 and Equation 2 as suggested by Avdeef [48]: where A is the filter area (0.24 cm2), t is

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• of Lewis acid–base bifunctional catalyst (Zr-β zeolite and K2CO3) in the Meerwein–Ponndorf–Verley reduction of a concentrated furfural solution (17.3–80.5 wt % in ethanol) combined with in situ cross-aldol condensation with acetaldehyde and crotonization. Ethanol was used as hydrogen donor for the

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

• donor, securing the desired secondary alcohol product in excellent enantioselectivity (99% ee). Protection of the alcohol group with TBDPSCl gave silyl ether 64 in high yield (79% for 2 steps). Subsequently, successive four manipulations including dehydrogenation, Morita–Baylis–Hillman reaction

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

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• efficiency observed upon switching from blue to UV-A light irradiation. Nevertheless, alternative scenarios involving the potential formation of excited donor–acceptor (EDA) complexes between benzoylazolium species 1 and DIPEA were considered. Measurements of the UV–vis spectra in the presence of the amine

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

• Lewis acid-mediated semi-pinacol rearrangement, this work involved a CRL-catalyzed desymmetrization of prochiral diol 51 (prepared from aldehyde 50 in four steps), providing monoester 53 in 57% yield with 83% ee. Notably, 1-ethoxyvinyl 2-furoate (52) was selected as the acyl donor in this step to

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

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• halogen may act as an electron donor rather than an acceptor, and the interaction can be better described as an n–π* interaction involving the lone pair on the halogen atom. The results shown in Figure 1 suggest that in the case of chiral compounds, the corresponding racemic and enantioenriched forms

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• addressed using counterpoise corrections. Natural bond orbital (NBO) analysis was conducted using the NBO 7.0 program [25] to identify donor–acceptor interactions responsible for electron delocalization within the systems. The NOSTAR/NBODEL keyword was employed to calculate deletion energies by excluding

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

• precursors [38][39][40][41][42]. This emphasizes the importance of reliable and reproducible approaches for the stereoselective synthesis of unsymmetrically orthogonally protected nonreducing disaccharides. While the desired anomeric selectivity on the side of the glycosyl donor can often be achieved by

• reactivity of the donor molecules [45][46][47][48]. Review Synthesis of β,α-1,1'-linked disaccharides The assembly of β,α-1,1'-linked disaccharides has traditionally been carried out using perbenzylated monosaccharide building blocks and various types of glycosyl donors, including chlorides [49], bromides

• [50], and trichloroacetimidates [51][52]. However, the monosaccharide components were mostly fully benzylated or acetylated, so that the 1,1'-glycosylation reactions led to the formation of symmetric nonreducing products [53]. For instance, the tetrabenzylated chloride donor 1 was reacted with the

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 one-pot synthesis approach was applied to successfully and quickly construct disaccharide 10. In this protocol, donor 7 was first activated by the TolSCl/AgOTf promoter and reacted with 6 to form compound 8. The reaction progress was monitored by thin-layer chromatography. Subsequently, in the

• same reaction mixture, in situ activation of disaccharide donor 8 and acceptor 9 using TolSCl/AgOTf reagent combination was introduced. This two-step, one-pot glycosylation gave a 42% yield of disaccharide 10, maintaining good β-stereoselectivity at the galactosyl linkage (α/β = 1:5.8). The 2

• position of the galactoside using 1.3 equivalents of bis(trimethylsilyl)amine (HMDS), concurrently leaving the 3-OH group at the non-reducing end available for glycosylation with the ᴅ-Galf donor 12 [47]. After the in situ activation with TolSCl/AgOTf, product 13 was obtained with a 76% yield and exclusive

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

• Scientific) and readily available in bulk quantities compound. In organic synthesis, it is most commonly used in metal-catalyzed reductions where NaH2PO2 serves as a molecular hydrogen donor [6][7][8][9][10][11][12][13][14][15][16]. However, recent studies demonstrated application of hypophosphites as a

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• is worth noting that the presence of a hydrogen bonding donor in 27 is crucial for achieving high enantioselectivity. As shown, while replacing the OH with NHMe led to a slight decrease of ee (28c versus 28b), the protection of the OH with methyl caused a severe drop (28d versus 28b). The application

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• catalysis, and this arsenal of catalysts is constantly expanding. In this thematic issue, the Dell’Amico group describes the development of a new class of organic donor–acceptor photocatalysts that show promising activity for several transformations [18]. Additionally, Hoffmann and co-workers contributed a

• Review article discussing photocatalysts capable of harnessing low-energy red light to trigger chemical reactions [19]. In addition to photoredox catalysis, several mechanistic platforms that leverage light – such as the use of electron donor–acceptor complexes [20], proton-coupled electron transfer [21

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

• used in the synthesis of a good number of target molecules, including complex natural products [32][33][34][35]. Typically, the LA binds the dienophile through a donor–acceptor interaction (usually involving a carbonyl group) which results in a significant stabilization of the dienophile’s LUMO. As a

• TS-aromaticity and the barrier heights. The origin of the computed decrease of the activation barrier in the CH3–OH to O=CH2 as compared to the analogous reaction involving ethane as hydrogen donor can be initially traced to different C–H vs O–H bond strengths. Indeed, we found that the total bond

• ) between them (as confirmed by the EDA method, Figure 6b). Obviously, this stabilizing noncovalent interaction is lacking in the process involving ethane as hydrogen donor and as a consequence, the activation barrier computed for this DGTR is substantially higher (although the in-plane aromaticity of the

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

• donor–acceptor dyads based on perylene (Pe) and phenothiazine (PTZ), in which triphenylamine (TPA) units and a phenyl spacer were introduced to modulate donor strength and spatial separation. Among the series, Pe–PTZ(TPA)2 exhibits a distinct thermal equilibrium between the locally excited (LE) state of

• the PTZ moiety and the photoinduced charge-transfer (CT) state. Femtosecond to microsecond transient absorption spectroscopy reveals that this equilibrium is facilitated not simply by enhanced donor ability, but presumably by excited-state planarization of the PTZ moiety, which lowers the energy of

• the LE state of the PTZ moiety. In contrast, Pe-Ph–PTZ(TPA)2, in which the donor–acceptor distance is increased by a phenyl spacer, does not show clear equilibrium behavior. These results underscore the crucial role of excited-state structural relaxation in tuning photoinduced charge separation, and

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• was employed. The substantial impact of the reaction conditions can be attributed to the stability of the dipole formed. The presence of mesomeric donor substituent (such as 4-OMe group) has been shown to render nitrile oxides more susceptible to dimerization in comparison to other dipoles [27][34

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

• peripherally modified CBBC derivatives have also been prepared and were shown to have fascinating properties [17][18][19][20][21]. For example, carbazole-substituted donor–acceptor-type CBBC derivatives exhibit both efficient circularly polarized luminescence (CPL) and thermally activated delayed fluorescence

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• conjugated systems, enabling the design of donor–acceptor helicenes with tunable photophysical properties. In 2020, Ema and co-workers developed a series of chiral carbazole-based BODIPY analogues 35a–f, derived from helical carbazole-based BF2 dyes [49] (Table 11). These analogues exhibit red-shifted

• -performance chiral optoelectronic materials. In 2023, Zhang’s group introduced a new class of helically chiral double hetero[4]helicenes 74a and 74b exhibiting CP-TADF, constructed on a distinct donor–acceptor core architecture [88] (Table 25). These compounds demonstrate excellent configurational stability

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• spectra in toluene and CHCl3 are almost identical, with two intensive bands around 390 nm (assumed to E according to the simulated spectra, Figure S2) and 470 nm (assumed to KE/KK), which is rather surprising bearing in mind that chloroform, as a strong proton-donor solvent, always shifts the tautomeric

• achieved with the used substituents. Most of the substituents destabilize K with exception of the electron donor ones on position 4 and all in position 6. Again, the cyano group on position 5 is acting in the desired direction, but the effect is weak. Considering the fact that some substituents act

• donors in the phenyl ring, while N–NH is a donor, favored by acceptors in Ph [3][7][89]. Following this model, a suitable substitution in the Ph ring of 1 can stabilize or destabilized KE and KK in respect to E and K. This opens an additional channel for fulfilling the requirements for a clean switching