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

• only causes damage to the environment, but also greatly restricts further research for their pharmaceutical applications. Therefore, substantial synthetic efforts have been devoted towards the preparation of these valuable targets recently [8][9][10][11][12][13][14][15][16][17]. Rhodexin A was firstly

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• against Gram-positive bacteria), will be conducted in our laboratory. Cyclization reactions to segetalins A–H, J and K. The CD spectra of segetalins A–H, J and K. Preparation of segetalins A–H, J and K. Preparation of linear peptides for segetalins A–H, J and K. Supporting Information Supporting

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• remains a major challenge due to the strong hydration of anions. Here, we report the preparation of silica gel functionalized with covalently anchored bambusuril macrocycles. In aqueous solution, this material efficiently sorbs dicyanoaurate(I), the key anion in gold mining, even in the presence of

• carried out in nitrogen atmosphere. The dicyanoaurate concentration in solution was determined according to UV–vis spectra recorded with a CARY 60 spectrophotometer (Agilent Technologies). NMR spectra were recorded on a Bruker Avance III 300 spectrometer (300.15 Hz, 298.15 K). Preparation of SG-NHCO-BU1

• was filtered and thoroughly washed with DMF, water and methanol in order to remove byproducts and unreacted BU1. After air-drying, SG-NHCO-BU1 was obtained. Preparation of SG-BU1 For the preparation of SG-BU1 with electrostatically bound BU1 on the surface of silica gel, a-SG (0.9 g) was suspended in

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• , particularly the synergistic combination of N-heterocyclic carbenes (NHCs) with organic photocatalysts, has opened new avenues in molecular construction, particularly for the novel, practical preparation of carbonyl group-containing compounds [13][14][15][16]. These ubiquitous ketone, ester, and amide

• , and advanced optical and energy materials. Review Visible-light-driven NHC/4CzIPN-catalyzed reactions Recently, Shu and co-workers developed a direct and innovative preparation of highly functionalized aryl amide derivatives 3 from aryl aldehydes 1 and substituted imines 2 under mild conditions in the

• existing metal-catalyzed C–H bond functionalization methods (Scheme 3) [53]. Recently, Scheidt et al. discovered an NHC/organic photoredox-catalyzed three-component coupling reaction for the efficient and novel preparation of γ-aryloxy ketone scaffolds 12. This transformation builds on the emerging field

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• polyhydroxylated molecular framework has posed a significant synthetic challenge, impeding the preparation of derivatives for SAR exploration. In 2017, the Reisman group addressed this issue by drawing upon an analysis of Deslongchamps’s prior synthetic work [45] (Scheme 8). They hypothesized that utilizing an

• ). The synthesis commenced with the preparation of key cyclization precursor 98 via Barbier coupling and Babler–Dauben oxidative rearrangement. A pivotal palladium-catalyzed Heck/carbonylative cyclization then efficiently furnished the ABC tricyclic core 99. Notably, adding N-formylsaccharin under a CO

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• 2,4,4,6-tetrabromo-2,5-cyclohexadienone (TBCD) in CH2Cl2 followed by reaction with allyl alcohol, provided β-bromo acetal 5 in 30% overall yield starting from alcohol 6. With a successful preparation of the cyclization precursor 5, the designed nickel-promoted reductive tandem cyclization was pursued

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• modification of the base-catalyzed conditions reported by Kwok [53], where a stoichiometric plus additional catalytic amount of tetraethylammonium hydroxide base in DMSO solvent was used to promote tandem trimethylsilyl deprotection and cycloaddition in one preparation (Figure 3). Isolated yields of this

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

• . Nucleophilic substitution of the nitro group with sulfur nucleophiles, including thioacetate or disulfide anions as well as thioacetamide, yielded bis(thiophen-3-yl)disulfide and sulfide derivatives. The disulfide served as a suitable precursor for the preparation of 3-alkylthio-substituted thiophene-2,5

• cyclization to furnish the TT framework [2][23][24]. Despite the wide structural diversity of TT derivatives, 3-hydroxy-substituted analogues remain rare, with only a few synthetic strategies described for their preparation, as illustrated in Scheme 1. One such route involves sulfur insertion into a thiophen

• tolerated both electron-donating and electron-withdrawing groups on the aromatic ring, and the yields for this series ranged from 76% to 92%. Piperonyl mesylate was successfully used in the synthesis of compound 4g (92% yield), while thiophene-2-ylmethyl mesylate was used for the preparation of compound 4h

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• of LG and 1,3-butadiene (Scheme 3). The ratio of the resulting regioisomers was 5:3 in favor of the 5-methoxycarbonyl derivative 17a. The synthesized cyclopentane derivatives 17a,b, 18, and 19 may be useful for the preparation of iridoids and other biologically active cyclopentanoids. An alternative

• with MeONa or t-BuOK as base led to the formation of diol 29 with a yield of 40%, which is interesting for the synthesis of angeloside (31) [23]. An alternative preparation of diol 29 involved ozonolysis of the double bond in dioxolane 26 at −78 °C in methanol, followed by reduction of the ozonide with

• unprecedentedly highly oxygenated five-membered D-ring. These compounds exhibit potent anti-inflammatory and analgesic activity both in vitro and in vivo [44]. The synthetic method for the preparation of dactylicapnosines A (63) and B (64) was based on the known phenol 65 and involved the ring contraction of p

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• consisting of a combination of isoxazolidine rings [36][37][38][39][40][41]. It has been demonstrated that such cycloaddition reactions are also employed in the efficient preparation of biologically active molecules, including nucleosides, β-lactam class antibiotics, peptides, and amino acids, as well as

• for the preparation of such cyclic compounds and/or their fused cyclic systems typically necessitate the use of toxic solvents, including chloroform, benzene, toluene etc. [32][53][54][55][56][57][58][59]. Indeed, the selection of conventional organic solvents, including benzene, toluene and

• -based nitrone with some maleimides via a mechanochemical route in a solvent-free medium [67][68]. The development of environmentally friendly green methodologies for the preparation of heterocyclic compounds via such cycloaddition reactions is a significant and ongoing research area that should not be

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• , The Ural Branch of Russian Academy of Sciences, Goleva St. 13, 614081 Perm, Russian Federation 10.3762/bjoc.21.183 Abstract A synthetic strategy for the preparation of spiro[indoline-3,2'-pyrrolidine] derivatives has been developed, featuring a two-step sequence consisting of the reaction of 2

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• pyrrolidine-derived phenyl keto amide substrate 91 with blue LEDs produces the pyrrolidine-fused 4-oxazolidinone (N,O-acetal) 92, precluding preparation of the pyrrolidine analog of lycoplatyrine A (94) by this method. Compound 92 is presumably formed via either the radical mechanism [41] or possibly

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

• larger aromatic walls in the form of triphenylene walls. To ensure that the targeted hosts display low aqueous solubility required for solid state sequestrants, we exchanged the O(CH2)3SO3Na groups for OMe groups. Accordingly, we targeted the preparation of W1 and W2 (Scheme 1) which contain large π

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

• -derived bioactives. Preparation of chlorinated and brominated lactones 8a,b and 11a,b. Preparation of fluorinated lactone 14. Fluorination of LGO (5) and conversion to lactone 17. Trifluoromethylation of 9a,b and 15 and subsequent Baeyer–Villiger oxidation. Supporting Information Supporting Information

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

• preparation of chiral β-aminoalcohols [63]. Chiral copper(I) complexes convert imidate radicals, formed transiently through energy-transfer catalysis, to oxazolines. The transformation includes a regioselective and enantioselective HAT process. Upon blue LED irradiation, oxime imidates (derived from alcohols

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

• components such as solvents, catalysts, ligands and so on. Unlike traditional “one-to-one” reactions, pathway-controlled “one-to-many” transformations synthesize multiple products from single intermediates, dramatically reducing preparation time and reagent requirements (Scheme 1b). As an exceptionally

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

• ]. Results and Discussion Chemical syntheses The synthetic strategy is very similar to the one previously developed for the preparation of DB18 and designed analogues (Scheme 1) [23][24]. It starts from known quinazoline 1 which, on Buchwald–Hartwig-type reaction with 3-bromoaniline (2a), gave

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

• . (a) Synthetic (2S,3S)-8, (2S,3R)-9, (2R,3R)-10, and (2R,3S)-11 and (b) C9–C12 fragment 7 derived from 1. (A) General strategy for the preparation of the fragment from an MPO-containing natural product. (B) Synthesis of esters 4–6, each as a mixture of four stereoisomers. Preparation of the C9–C12

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

• , most synthetic methods have focused on the preparation of symmetric derivatives [12][13]. Traditional approaches, such as oxidative coupling of anilines [14][15][16][17][18][19], reductive coupling of nitroarenes [20][21][22][23], or cross-coupling between anilines and nitroarenes have proven

• proved to be a suitable coupling partner, enabling the preparation of azoarene 3p in 70% yield. Moreover, starting from 1,4-dibromobenzene and 2 equivalents of 1a, a double reaction occurred, enabling the one-step synthesis of 1,4-bis[(E)-2-phenyldiazenyl]benzene (3q) in high yield. We next investigated

• -products. The presence of oxidants such as O2 mitigates this pathway by promoting oxidative dehydrogenation as the dominant pathway. Conclusion In summary, we have developed robust and efficient conditions for the preparation of azobenzenes via C–N coupling and dehydrogenation, employing [PdCl(C3H5)]2 with

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

• -dioxides, we aimed at elaborating a synthetic procedure for the preparation of their pyrrole-fused counterparts, 2,9-dihydro[1,2,3]thiadiazino[5,6-g]indole 1,1-dioxide derivatives. The simple and versatile process led, via Fischer indole cyclization of the corresponding hydrazones, to a wide structural

• KGaA, Darmstadt, Germany), adjusting the pH with HCl. Water for buffer and eluent preparation were provided by a Millipore Milli-Q water purification system. Kinetic aqueous solubility assay. All compounds were dissolved in DMSO to make stock solutions at 10 mM concentration. In the case of 7i, 7j, and

• water (5 mL) was added. The mixture was extracted with EtOAc (3 × 5 mL), washed with water (5 mL) and brine (5 mL), dried over MgSO4 and evaporated to give crude products 3 or 10, which were purified by recrystallization from isopropyl alcohol or by flash chromatography. Method B for the preparation of

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• sustainable strategy for the preparation of 3-selenylindoles. In 2023, Satyanarayana also described a similar electrochemical cascade approach towards 3-selenylindoles from 2-alkynylanilines (Scheme 6) [202]. When graphite was used as anode, platinum as cathode and LiClO4 as electrolyte, the electrochemical

• ][254], this approach exhibited the following advantages like without metal catalysts and external oxidants, atom economy, facile access of starting materials, etc. In 2024, Cho succeeded in the preparation of trifluoromethylated oxazoles through in-situ aminotrifluoromethylation/cyclization of alkynes

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

• the atom economical preparation of dihydroxyacetone (DHA) in good yield from aqueous glyceraldehyde (Scheme 16) [78]. Transformation of 1,3-dihydroxy-2-propanone (dihydroxyacetone, DHA) has been a very popular topic for many years, using a variety of reactions like isomerizations and dehydrations [79

• intermediate furan-derived enones. Subsequent reductive amination was performed in the presence of ammonia or amines and Pd/Al2O3 under H2 pressure, providing the tetrahydrofuran-derived amines [184]. The same catalytic system could allow the one-pot preparation of tetrahydrofuran-derived secondary and

• , pharmaceuticals or high added value chemicals [215][216][217][218][219][220][221][222][223]. Its first commercial production began in the 1940s. Its preparation from biomass involves several different possible pathways. One is the C5 sugar route starting from xylose as an example, relying on acid hydrolysis of

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

• , unlike conventional linear synthesis strategies, they enable the preparation of libraries of organic compounds in higher yields and with significantly less time, resources, and chemical waste [1][2][3][4][5]. The Ugi reaction, discovered in 1959 by Ivar Karl Ugi [6], is one of the classic multicomponent

• for the preparation of benzodiazepinone derivatives, which showed promising psychotropic effects [20][21][22][23][24], using a tandem combination of Ugi/azide–alkyne cycloaddition reactions. From this point of view, azido amines are promising reagents for use in the Ugi reaction, opening up the

• dedicated to the synthesis of novel peptidomimetics using the four-component Ugi reaction and the study of a tandem Ugi/aza-Wittig combination based on α-ketoglutaric acid for the preparation of earlier unavailable quinoxalinone derivatives. Results and Discussion We began by studying the behavior of α

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• -keto ester 15 [24]. The β-keto ester 15 was expected to be derived from compounds 16 and 17 via an asymmetric aldol reaction [25]. The first phase of the synthesis required the efficient preparation of compound 14, for which a transition-metal-mediated oxidative radical cyclization of β-keto ester 15

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

• -worker described the asymmetric synthesis of (−)-rasfonin, harnessing an enantioselective enzymatic desymmetrization with lipase AK and an enzymatic oxidative kinetic resolution to install stereocenters [47]. The synthesis commenced with the preparation of fragment 100 from ethylene glycol (97) (Scheme

• leustroducsin B (96). Nanda’s synthesis of a) fragment 100, b) fragment 106 and c) (−)-rasfonin (109). Davies’ synthesis of (+)-pilocarpine (115) and (+)-isopilocarpine (116). Ōmura’s synthesis of salinosporamide A (125). Kang’s synthesis of ʟ-cladinose (124) and its derivative. Kang’s preparation of fragment