Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• moiety have been isolated and demonstrate potent bioactivities [7] (Figure 1). For example, lactacystin (1) which was isolated by Ōmura and co-workers [8][9], is a potent and selective proteasome inhibitor; its active form is the synthetic precursor omuralide (2) [10][11]. Similarly, salinosporamide (3

• ), a marine natural product isolated by Fenical and co-workers [12], also acts as a proteasome inhibitor and displays more potent in vitro cytotoxicity than omuralide (2). Anisatin (4), which contains a characteristic spiro β-lactone has been identified as a noncompetitive antagonist of GABA-gated ion

• channels [13]. Tetrahydrolipstatin (5) is a potent pancreatic lipase inhibitor and has been developed into an antiobesity drug marketed under the generic name Orlistat. Vibralactone (6), which was isolated by Liu and co-workers from Basidiomycete Boreostereum vibrans, features a fused β-lactone with a

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

• methoxide anion (Figure 2). The neutral acridane is restored through the thermal nucleophilic attack of the alkoxide on the acridinium ion. Abraham and co-workers exploited this dramatic change in the electronic nature and geometric shape of acridane to modulate the translation of cyclobis(paraquat-4,4

• behavior, enabling the translation of the macrocycle along the axle upon irradiation with light (Figure 3) [21]. Anthracene Anthracene undergoes [4π + 4π] dimerization upon irradiation with light, whereas cycloreversion is achieved thermally (Figure 2) [27]. Tron and co-workers synthesized a [2]rotaxane

• isomerization (Figure 2) [29]. In 1997, Nakashima and co-workers reported the first rotaxane where the azobenzene was located on the axle, acting as a recognition site for a β-cyclodextrin macrocycle. Photoisomerization of the azobenzene controlled the shuttling of the macrocycle [30]. Later, Stoddart and co

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

• isolated by Kobayashi and co-workers from the club moss Lycopodium complanatum [4][5][6][7]. They discovered that complanadine A exhibited neurotrophic activity by enhancing the mRNA expression level for nerve growth factor (NGF) biosynthesis in 1321N1 human astrocytoma cells and NGF production in human

• glial cells, rendering complanadine A a promising lead compound for neurological disorder treatment. Later, complanadine A was also identified as a lead compound for pain management by Siegel and co-workers [8]. They discovered one of its potential cellular targets as the Mas-related G protein-coupled

• and co-workers [19]. In this review article, we summarize these four total syntheses, comparatively analyze their strategic novelty and differences, and highlight the impact of enabling methodologies and concepts on the overall efficiency and economy of each total synthesis [20]. Review The Siegel

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• ], and non-conventional adsorbents [14]. Although activated carbon is widely used, its ability to capture polar compounds is limited and the regeneration process is complex and energy-intensive [15]. In work that stimulated supramolecular chemists to enter the game, Dichtel and co-workers demonstrated

• that β-cyclodextrin (Figure 1)-based polymers could remove organic micropollutants from water [15][16]. For example, in 2021, Sessler and co-workers reported the synthesis of a calix[4]pyrrole (Figure 1)-based porous organic polymer, which exhibits the rapid uptake of dyes from water [17]. In addition

• found that the water-soluble naphthalene-walled glycoluril dimer G2M2 (Figure 1) – with its roughly co-planar aromatic walls – is selective for planar aromatic cations as guests [38]. In order the complement the tricyclic ring system present in the panel of dyes (Figure 2), we envisioned the use of even

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• infections. The preparation of 2-halo-2-deoxy-ᴅ-ribose derivatives can be achieved via the modification of the parent sugar [9][10] or chain-elongation strategies from lower homologues. For example, Castro and co-workers have demonstrated the synthesis of a dichlorinated 2-deoxypentose via the addition of

• species in situ was crucial for this transformation. By modifying a procedure for the trifluoromethylation of ketene dithioacetals reported by Liu and co-workers using TMSCF3 [43], rapid consumption of enamine 15 was observed. Acidic treatment of the intermediate promoted the hydrolysis/elimination

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

• transformations [43][44][45][46][47][48]. Using SOMO catalysis, MacMillan and co-workers developed a method for the synthesis of substituted pyrrolidines from β-aminoaldehydes and olefins in a formal [3 + 2] cycloaddition (Scheme 2) [44]. The transformation was proposed to proceed via a radical–polar crossover

• single process that established five new carbon–carbon bonds and nine contiguous stereocenters, including four all-carbon quaternary centers (Scheme 3). Transition-metal-catalyzed radical reactions Recent advances in enantioselective radical reactions catalyzed by base metals (e.g., Fe, Co, Ni, Mn

• and NiCl2·diglyme, was used as the catalyst to obtain the coupling products 20 in good yield and high enantioselectivity. The first nickel-catalyzed asymmetric reductive cross-coupling reaction between acid chlorides 21 and secondary benzylic chlorides 22 was reported by Reisman and co-workers (Scheme

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

•  2, path b). In the following years, Liu and co-workers discovered that the protonation of intermediate 2 triggered its conversion to intermediate 3, which subsequently underwent oxidation with oxygen, resulting in the generation of an indenone skeleton 6 [9]. This tunability achieved efficient and

• and co-workers achieved an innovative gold-catalyzed cascade cycloisomerization of 3-allyloxy-1,6-diynes to access cyclopropane- and cyclobutane-fused benzofurans/chromanols (Scheme 5) [12]. In this study, solvent polarity and trace water were identified as key parameters governing the reaction

• nexus for the rational design and optimization of highly effective, selective homogeneous catalytic systems. In 2013, Barriault and co-workers demonstrated that strategic modulation of steric and electronic ligand parameters within gold(I)-catalyzed cyclization pathways enables the selective assembly of

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• obtained suffered from co-evaporation during solvent removal under reduced pressure, which led us to consider that degradation of the natural product to obtain the corresponding fragment would be challenging. Accordingly, esterification of the hydroxy group at C3 in 3, and suitable acyl groups were then

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• and co-workers developed a Chan–Evans–Lam-type oxidative cross-coupling reaction between N-arylphthalic hydrazides and arylboronic acids using copper catalysis [41]. Similarly, in 2003, Lee and co-workers introduced a desymmetrization approach employing simpler N=N precursors, specifically N-protected

• hydrazines. Their method involved a three-step process comprising Cu and Pd-catalyzed C–N bond formations followed by a dehydrogenative deprotection step (Figure 1b, top) [42]. This desymmetric approach was further employed by Oestreich and co-workers in 2022, who introduced silicon-masked diazenyl anions in

• for synthesizing non-symmetric azobenzenes via a Pd-catalyzed cascade involving C–N coupling of arylhydrazines with aryl bromides, followed by oxidative dehydrogenation (Figure 1c). As our study was nearing completion, Váňa and co-workers disclosed a related Buchwald–Hartwig approach employing the Pd

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

• al. reported the valorization of C1 molecules (CH4, CO2, and CO) upgraded to the industrially important C2 chemical glycolic acid (GA) in a sustainable way. In the first step all the C1 source molecules are converted into formaldehyde. Metabolic engineering of E. coli-based biocatalysts allowed to

• . Polylactic acid (PLA) and polyglycolic acid (PGA) are most important examples of biopolymers exhibiting interesting biodegradability properties [41]. The co-polymerization of PLA with glycolic acid was reported by Ayyoob and Kim [42]. High molecular weight poly-lactic-co-glycolic acid (PLGA) was obtained by

• the direct condensation and co-polymerization of both monomers promoted by a bicatalytic system including stannous chloride (SnCl2·2H2O) and methane sulfonic acid (MSA). PLGA films were prepared by the solvent casting technique, for which the presence of glycolic acid was found to increase their

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

• co-workers accomplished the first asymmetric total synthesis of (+)-aplysiasecosterol A (6) by employing a desymmetric enantioselective reduction strategy of 1,3-cyclopentanedione derivative as the key transformation [14]. Their synthesis features a highly efficient desymmetric enantioselective

• ][44][45][46][47][48][49][50]. For an efficient synthesis of these two natural products, Han and co-workers [51] adopted an alternative route utilizing the desymmetric enantioselective reduction strategy of a 1,3-cyclopentanedione derivative as the key transformation. Both (−)-hamigeran B (11) and

• 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

Multicomponent reactions IV

• Thomas J. J. Müller and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2082–2084, doi:10.3762/bjoc.21.163

• issue (1 Letter, 22 Full Research Papers, and 7 Reviews) reflect the broad spectrum of MCR chemistry worldwide. Among the Full Research Papers, isocyanide-based multicomponent reactions still constitute the relative majority. Ugi and co-workers’ groundbreaking discovery of the four-component reaction

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• fungus Aspergillus versicolour SCSIO XWS04 F52 [32]. All these alkaloids distinguish each other only by alkyl substituent at C11 and by relative stereochemistries at C2, C3, C11, and C14. Soon after the report of the isolation, structural elucidation, and bioactivity of (–)-chaetominine by Tan and co

• structures of aspera chaetominines A and B and revision of stereochemistry of aspera chaetominine B Several years after we have had accomplished the abovementioned investigations, Liu and co-workers reported the isolation and structural elucidation of two new alkaloids, aspera chaetominines A (12) and B (13

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• synthesis of natural products. Review Synthesis of chabranol In 2009, Duh and co-workers investigated the ingredients of Formosan soft corals Sinularia capillosa Tixier-Durivault and Nephthea chabroli Audouin, collected from west pacific Dongsha Atoll and Siaoliouciou Island, providing two terpenoid natural

• with an acid and base-promoted saponification inversed the C12 alcohol stereochemistry, which ultimately provided (12R)-hydroxymonocerin. Total synthesis and bioinspired skeletal diversification of (12-MeO)-tabertinggine In 2013, Kam and co-workers reported the discovery of two novel indole alkaloids

• chinensis Decne and Gymnotheca involucrate Pei. These two plants are endemic in China, and have been used as medicinal herb for a long history to treat diseases such as dysentery, abdominal distention, edema, contusion, and strains [31]. Since 2012, Zhou and co-workers extensively investigated the

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

• [8]. Significant progress has been made in developing molecular photochromic systems for solar thermal energy storage, with representative examples including anthracene derivatives [9][10][11], diphenylethylene [12][13], fulvalene-based tetracarbonyldiruthenium (FvRu2(CO)4) [14][15][16

• enables each azobenzene unit to store >200% more energy than isolated molecules, while achieving multi-order-of-magnitude improved storage lifetime and resistance to material degradation during repeated cycling. Feng and co-workers covalently grafted azobenzene groups onto RGO templates (Figure 3b) and

• visible light under sunlight irradiation [59], achieving a solar efficiency of 0.4% and a solid-state isomerization efficiency of 72.7% (Figure 5b). Feng and co-workers reported the synthesis of three azopyridine polymers (ortho-, meta-, and para-) [60], with the m-azopyridine polymer exhibiting a

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

• producing energy-dense compounds [2][3]. One promising strategy to access strained compounds involves gas-evolution (e.g., CO or N2) because of the associated entropic driving force; this approach has had wide utility in photomedicine and organic synthesis. For example, photochemical decarboxylation has

• 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

• to experimentally measure the stereoselectivity of the reaction. In 1965, Crawford and co-workers experimentally found kinetic evidence for a 1,3-diradical from the thermal decomposition of 1 [56]. In 1963, Steel investigated the photolysis of diazabicyclo[2.1.1]hep-2-ene in solution, and the

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

• manifold with carboxylic acid derivatives, numerous coupling processes affording ketone products have been developed. Since the initial report from Scheidt and co-workers using 4-alkyl-substituted Hantzsch esters as coupling partners [31][32][33][34][35][36], several alkyl radical sources have been

• recently proposed by Marzo and co-workers in an NHC-mediated coupling reaction with alkyl halides mediated by (TMS)3SiH [55]. The O-silylated product 5 could result from a subsequent radical C-silylation followed by a Brook-type rearrangement process [56]. Interestingly, performing the TESH-mediated

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

• in intramolecular [7-exo] and [8-endo] cyclization, furnishing the 7-membered cyclic ether 40 and 8-membered cyclic ether 41, respectively. Finally, MOM deprotection produced (−)-heliannuol D (42) and (+)-heliannuol A (43). In 2002, Chênevert and co-workers completed the total synthesis of (S)-α

• Takabe and co-workers in their synthesis of (E)-3,7-dimethyl-2-octene-1,8-diol (isolated from Danaus chrysippus) (Scheme 10) [42]. Prepared from geraniol (61) in eight steps, diol 62 was converted to enantioenriched compound 63 in 75% yield with 90% ee in the presence of PSA. This intermediate was

• further advanced to (E)-3,7-dimethyl-2-octene-1,8-diol (64) over three steps. Later in 2004, Takabe and co-workers accomplished the asymmetric synthesis of variabilin, a marine-derived furanosesterterpene (Scheme 11) [43]. The key C18 chiral center was established through lipase-mediated asymmetric

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

• diverse co-substrates. A high-throughput approach was used to identify promising substrate/co-substrate/catalyst combinations which were then prioritised for purification by mass-directed HPLC to yield a total of thirty reactive probes. The structural diversity of the probe set was increased by the

• multiplicity of reaction types between rhodium carbenoids and the many different co-substrate classes, and the catalyst-driven selectivity between these pathways. The probes were screened for activity against Trypanosma brucei, and four probes with promising anti-trypanosomal activity were identified

• the reactive probes would be prepared by dirhodium-catalysed reactions between pairs of building blocks: an α-diazoamide 2 bearing a S(VI) electrophile and a suitable co-substrate (→ 3) (Figure 1). Here, metal-catalysed carbenoid chemistry was chosen because of the wide range of potentially reactive

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• University of Hong Kong (HKU) and ITC to the SKL. The work described in this paper was partially supported by a grant from the Co-funding Mechanism on Joint Laboratories with the Chinese Academy of Sciences (CAS) sponsored by the Research Grants Council of the Hong Kong Special Administrative Region, China

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• -diimines. Later, in 2001, Yudin and co-workers described the parallel reductive coupling of aldimines using a spatially addressable electrosynthesis platform, which employed a stainless steel cathode, a sacrificial aluminum anode and a procedure adapted from Torii's earlier work including the use of PbBr2

• co-workers [44], the presence of a strong protic acid, such as methanesulfonic acid, MsOH, is essential to promote the intramolecular coupling. A control experiment revealed that when the electroreduction of 1a was performed in the absence of MsOH (Table 1, entry 3), no formation of the desired

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

• ][10][11][12][13]. Of note, Cook and co-workers described an elegant approach using tryptophan as a starting material and an oxidative rearrangement of an indole that allows access to a variety of spirooxindole alkaloids from the Alstonia genus [14]. An efficient way to construct cyclic nitrogen

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

• , the application of CPA catalysis in the asymmetric synthesis of other forms of molecular chirality has received less attention. While List and co-workers reported the first CPA-catalyzed asymmetric synthesis of helically chiral azahelicenes through the Fischer indole synthesis back in 2014 [12], the

• approaches [20]. In 2014, List and co-workers reported the pioneering CPA-catalyzed asymmetric synthesis of helically chiral molecules, which also marked the first organocatalyzed asymmetric synthesis of such compounds [12]. By employing a CPA-catalyzed asymmetric Fischer indolization reaction of hydrazine 1

• , while utilizing MnO2 as an oxidant selectively yielded heterohelicenes 20 with bisamido substitution at the peri-positions. In 2024, Zhou, Chen and co-workers disclosed an efficient method for the asymmetric synthesis of indolohelicenoids through a sequential enantioselective annulation, followed by an

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• catalytic performance and/or systematically investigate the influence of a particular chemical or structural property on catalyst efficiency [23]. For examples of tailoring the pore environment in MOF-based catalysts to modulate catalytic performance, we can refer to the elegant work of Telfer and co

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

• the protein-binding site than the bent Z-isomer. However, it would be more desirable to have an inactive molecule in its most stable state which can be activated by irradiation [51][59]. Hernando and co-workers were able to design photoswitchable neurotransmitters of ionotropic kainate receptors by

•  14, box) and repulsion between the aryl and the carbonyl group in the E-isomer. Some studies on N-acylindigo derivatives reported, besides the expected spectral blue-shift, also a decrease in the fatigue resistance due to photochemical rearrangements [68][69]. Dube and co-workers reported a series of

• racemised upon irradiation. For further details about bridged indigos, we refer the reader to the work of Tsubaki and co-workers [71]. Although less pronounced, substituents in the phenyl ring also change the absorption properties of indigos. Considering only the resonance structures that involve the phenyl