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

• elastase release and superoxide-anion generation. In 2024, Baudoin and co-workers presented an efficient route for the first total synthesis (+)-randainin D (13) by utilizing an early-staged Ru-catalyzed desymmetric enantioselective reduction as the key transformation [53]. As shown in Scheme 5 [53], based

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

• comparisons highlight future directions for cross-material integration. The reversible trans–cis isomerization of azobenzene makes it an ideal model system for studying solar thermal fuels, as it enables both solar energy storage and heat release. While significant advances have been made, critical challenges

• , and hinders practical deployment. Third, azobenzene groups release energy through a process involving thermal relaxation or thermally induced cis–trans isomerization. Temperature critically governs the efficiency and kinetics of this process: elevated temperatures accelerate uncontrolled instantaneous

• heat release, while low temperatures induce phase transition-induced failures that compromise structural stability. Despite tunable photothermal parameters, achieving controlled heat release and structural robustness under extreme temperatures remains a pivotal challenge for azobenzene systems. Looking

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

• been employed to release carbon monoxide at relatively safer doses in biological systems using photoresponsive CO-releasing molecules (photo-CORMs) [4] because these have shown anti-inflammatory activity [5][6]. Photochemical denitrogenation of azoalkanes has been utilized in the stereoselective

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• inherently chiral eight-membered azaheterocycles 72 with moderate to good enantioselectivity, along with the release of CO2 (Scheme 20). While the enantioselectivity using certain substrates was initially unsatisfactory, simple phase separation significantly enhanced the enantiopurity of the products by

• 71 yielded the cyclic intermediate INT-B, which then underwent addition with aniline co-catalyst 73 to form INT-C. The CPA-enabled release of CO2 from INT-C yielded the imine-containing intermediate INT-D, which underwent iterative addition with INT-B, followed by release of CO2 to afford INT-E. The

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

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

• Liu-Huan Yi Jian Qin Si-Ran Lu Liu-Pan Yang Li-Li Wang Huan Yao School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, China 10.3762/bjoc.21.139 Abstract Intelligent controlled-release drug delivery systems that are responsive to various external

• release systems based on host–guest selective recognition, self-assembly, and nano-valves by the use of of calixarenes and pillararenes from five perspectives: pH, light, enzyme, hypoxia, and multi-stimuli combination responses. Furthermore, the article projects the future clinical application prospects

• of controlled-release technologies, with the aim of offering a reference for the utilization of aromatic macrocycles in drug-controlled release applications. Keywords: aromatic macrocycle; controlled-release drug delivery systems; stimulus response; supramolecular chemistry; Introduction Drugs are

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• (e.g., safety) and fundamental challenges (e.g., mass/heat transfer limitations). Process safety assessment: Nitration reactions pose significant safety risks due to their highly exothermic nature (ΔH ≈ −73 to −253 kJ/mol) [35], which can trigger thermal runaway if heat release is uncontrolled, and the

• the material [70]. Oxygen balance (OB), a critical parameter quantifying how well an explosive provides its own oxidant, reveals potential safety risks when OB values exceed the threshold of −200. Since the energy release predominantly originates from oxidation reactions, the available oxygen content

• in a nitric acid/acetic anhydride system under semi-batch conditions, revealing an average reaction enthalpy of −173.63 kJ·mol−1 – significantly more exothermic than conventional nitration processes, with this enhanced exothermicity likely arising from concurrent heat release during acetic anhydride

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• antitumor agent PI-88 (muparfostat), which retards tumor growth via inhibiting angiogenesis in two ways: 1) interaction with pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) and 2) by prevention of the release of angiogenic growth factors

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• switches with multiple states [3], logic-in-memory operations using single-metallofullerenes [4], multistate molecular switches [5], molecular memory and logic processing based on guest capture/release [6], etc., have demonstrated the possibility of using single molecules in logic operations. Manipulating

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• released by microorganisms into their surrounding extracellular environment to chelate iron and selectively import it into the microbial cells [12][13]. It has been suggested that the release of siderophores by soil-dwelling pseudomonads give them an ecological edge by creating an iron-deprived environment

• ]. The biosynthetic route of compound 1 leads to the amide-bond formation step between the PmsG-tethered threonine and salicylic acyl group leading to intramolecular dehydration. The decarboxylated product of histidine, histamine serves as a nucleophilic substrate to release the corresponding uncyclised

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

• 175 in a divergent synthesis of 3,3-disubstituted oxetane amino esters 176 based on a facile, strain-release-driven Giese addition of nitrogen- or oxygen-stabilised radicals (Scheme 44) [96]. The radicals were generated through a photochemical oxidative decarboxylation of amino- or alkoxycarboxylic

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• radical anion 15 was reduced by the photocatalyst Ir(Fppy)3 from the reagent 11. The resulting anion 14 underwent aromatization to release a nitrile anion, subsequently yielding product 12. This strategy also successfully produced products 16 and 17 with yields of 85% and 56%, respectively, from

• able to abstract a hydrogen atom from substrate 1. The addition of the corresponding radical 4 to HRP-5 facilitated the release of amidyl radical 36, which simultaneously produced the final product 35. Amidyl radical 36 was capable of abstracting hydrogen atoms from both substrate 1 and AQ–H. The HAT

• radical 47 can be intercepted by species 43, simultaneously releasing radical 48 and product 44. Radical 48 reacts with HRP-6, leading to the regeneration of amidyl radical 45, the release of byproduct 49, and the initiation of a chain reaction pathway. Notably, this system could give rise to the

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• the starting material 28 to yield an alkyl radical intermediate 31. This radical undergoes C=C-bond addition, cyclization, and deprotonation, ultimately leading to the formation of the desired products. Simultaneously, MeOH is reduced at the cathode to release H2, maintaining the electronic balance of

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• carboxylate groups followed by a ring opening of the aziridine ring, forming azomethine ylide intermediates A. The intermediates A further undergo a [2 + 3] annulation (or cycloaddition) with aldehydes 2 through endo transition state TS to generate intermediates B, which release products 3 with regeneration

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

• using tris(2,4,6-trimethoxyphenyl)phosphine (TMPP) to obtain methyl cinnamate (44) in good yield (Scheme 18) [50]. Herein, the phosphine group attacks the acid fluoride to give intermediate 55, fluoride attack then triggers methoxy group release. Toste and co-workers (2021) synthesized N-trifluoromethyl

• trimethylsulfoxonium iodide (TMSOI) with DMSO-d6, resulting in CH3/CD3 exchange. Furthermore, Chisholm and co-workers (2019) synthesized bulky cinnamate esters 61–64 utilizing a trichloroacetimidate-based alkylating agent in moderate to excellent yields via carbocation 65 formation upon trichloroacetamide release

• ) utilized isothiocyanate and cinnamic acid (7) to prepare the corresponding amide 47 in good yield via a carbamothioic anhydride 74 formation followed by carbonyl sulfide (COS) release (Scheme 24A) [59]. Similarly, Zhao and co-workers (2020) employed tetraalkylthiuram disulfides to synthesize amides via COS

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

• ]. In 2015, García-Valverde and co-workers described an alternative synthesis of benzo[e][1,4]diazepines 6, exploring the nitro group of 2-nitrobenzoic acid as a masked amino group. The release was achieved through the post-Ugi reduction of the nitro group with SnCl2 triggering concomitant

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

• afforded phenanthridinones. Intriguingly, switching to the electron-rich bidentate ligand bis(diphenylphosphino)methane (dppm) redirected the pathway to yield acridones. Time-dependent NMR studies revealed that the selectivity hinges on the aryne release kinetics from its precursor. Employing CsF

• , oxidative addition of the C–I bond to palladium formed the four-membered aryl–palladium complex Int-5. Steric hindrance from the bulky dppm ligand, combined with slower aryne release (using KF as the fluoride source), attenuated aryne coordination. Under these electron-deficient conditions, CO

• to substrate 11, followed by oxidative addition and release of carbon dioxide to form the zwitterionic π-allylpalladium intermediate Int-21. Under the reaction conditions, silyl triflate 12 undergoes a fluoride-mediated 1,2-elimination to generate the cyclic allene intermediate Int-22. Through a

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• solution into chloroform and controllable release into acidic solution [32]. Very recently, it was found that the receptor L alone can further extract solid Li2SO4 into DMSO solution [33], where sulfate binding is sufficiently strong to drive the solid–liquid extraction. DFT calculations suggest that an

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

• isoforms of NOS named according to their site of existence and include inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS) [4]. For example, upon bacterial infection in humans, immune cells express iNOS which promotes the release of NO causing inflammation [5] and NO supports defense to

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• species Int C or Int D, which undergoes an SN2'-like pathway with allylic phosphates 23 to generate the chiral products 43 or 44 along with the release of L*CuOR species. A σ-bond metathesis of this alkoxycopper species with HBpin and/or PMHS regenerates the L*CuH catalyst, completing the secondary

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• trodelvy, used in a treatment for patients with triple-negative breast cancer, the linker may release the drug prior to internalization. (3) Payload: The payload may be a subunit used in cellular tracking, imaging, or most commonly toxic drug therapeutics. The overall goal of ADCs is to deliver the payload

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

• grinding serves to dissociate the more loosely bound 2.3 from 2.2, where a release of strain energy and formation of a more thermodynamically stable 2.1·2.2 complex for a subsequent turnover are favored. The first preparative example of photomechanochemistry via manual grinding was reported by Wang and co

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• release [216] and even switch catalysis on and off [196]. MOCs containing peptides in the edge pieces also look promising to direct catalysis [217]. Extended frameworks Metal-organic frameworks (MOFs) [218][219] and covalent organic frameworks (COFs) [220][221][222][223][224] are well-studied as

• that might permit tuning of several consecutive catalytic steps [395], induced-fit binding, product release, allostery [396][397], or signaling. For the acyl transfer reaction, cage 1 is an inferior catalyst compared to cage 2, which we have postulated is due to the larger equilibrium cage height

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• , red-light photocatalysis enables innovative applications in phototherapy and controlled drug release, exploiting its tissue penetration and low cytotoxicity. Together, these developments underscore the versatility and impact of red-light photocatalysis, positioning it as a cornerstone of green organic

• photocatalysts, such as helical carbenium ions and advanced nitrobenzofuran derivatives for applications in phototherapy and controlled drug release, underscoring the potential of red-light photocatalysis in biomedicine. Review Red-light photocatalysis with metal-based complexes Metal-based complexes naturally

• acetone, allowing the pre-activation of the ruthenium complex with the successive release of an N-heterocyclic carbene ligand and a chlorine atom, which are replaced by two acetone molecules to form compound 2. Simultaneously, excitation of the osmium(II) complex in the red region (660 nm) decreases its

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• a phenol moiety. The final step is assumed to be facilitated by the release of the ring distortion of the benzofuran system. Overall, triggered by the gold(I)-promoted 6-endo hydroamination between the 2,3-diaminobenzofuran and the alkyne in 11, dehydrogenative oxidation of the resulting 12 to form