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

• product. They resolved racemic intermediate 27 by derivatization with (S)-1-(1-naphthyl)ethyl isocyanate, followed by separation of the resulting diastereomers via silica gel chromatography (Scheme 3). By converting diastereomer 32 to (−)-illisimonin A, the absolute configuration of the natural product

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• monosaccharides and applying dipolar cycloaddition to construct various bioactive compounds [21][22][23][24][25][26][27], we intended to develop a practical strategy to access the perhydrofuropyran core of malayamycin A and other uracil nucleosides to enable future rapid derivatization (Scheme 1B). The bicyclic

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• spatiotemporal precision [9]. Rotaxanes have emerged as promising tools for performing various functions in lipid membranes, owing to their multiple sites for derivatization, which allow fine-tuning of their structure and function in membranes. For instance, they have been used to transport ions across lipid

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

• protocol highlights its potential for further derivatization and the discovery of valuable properties. Natural and synthetic bioactive spiro[indoline-3,2'-pyrrolidine] derivatives. Previous approaches and our work. The reaction of 2-arylindoles 1 with α,β-unsaturated ketones 2. aIsolated yield of the 5

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

• derivatization. Several derivatization methods using chiral anisotropic reagents, including α-methoxy-α-trifluoromethylphenylacetic acid (MTPA), phenylglycine methyl ester (PGME), and Marfey’s reagents, are widely used [8][9][10], although their applicability is restricted by the presence of specific functional

• Discussion Our degradation strategy of natural products bearing an MPO moiety includes (1) acylation of hydroxy group, (2) oxidative cleavage of olefin to generate 3-acyloxy-2-methylbutanoic acid, and (3) its methyl esterification (Scheme 1A). We initially investigated derivatization strategies to enable LC

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

• decyanation [75] and double bond migration of 95 produced common intermediate 96, which was elaborated to ketone 97 [69] via four functional group manipulations, thereby achieving the formal total synthesis of (−)-conidiogenone B (17). On the other hand, functionalization and derivatization were performed on

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• NH proton in the urea moiety (position N5) of indolo[1,2-c]quinazolin-6(5H)-one (1) enables efficient N-alkylation. Accordingly, alkylation of 1 with 1-bromo-3-chloropropane afforded intermediate 11, bearing a reactive chloropropyl side chain suitable for further derivatization. Nucleophilic

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

• DDD products 64e. Moreover, the authors showcased the facile derivatization of dimethoxy-substituted chiral DDD 64f into various DDD-based chiral ligands, such as the phosphoramidites 65, phosphoric acid as well as monophosphine ligands and diphosphine ligands 66. Notably, the applications of these

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• thermodynamically stable cis- and trans- isomers were also obtained in the reaction with azomethine ylides [20]. Finally, we performed preliminary derivatization studies of the obtained spiro-tetrahydrothiophenes. Compounds 7 and 9 demonstrated remarkable stability under both acidic and basic hydrolysis conditions

• , proved to be a more promising derivatization approach (Scheme 4). Thus, the short-term action of hydrogen peroxide successfully converted compounds 7e, 7c, and 9e to their corresponding sulfoxides 11e, 11c, and 13e. However, prolonged oxidation led not only to sulfone formation but also to deeper

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

• solubility, this can be improved through derivatization. Water-soluble calixarene derivatives can be obtained through functional modifications, including the introduction of sulfonic acid, amine, and carboxylic acid groups [57][58][59]. These water soluble macrocycle derivatives can be used to increase the

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

• excellent UV stability and solvent-dependent fluorescence [91]. Protonation significantly enhanced their emission intensity, and the presence of nitrogen facilitated further structural derivatization. In the same year, Alcarazo’s group reported an enantioselective gold-catalyzed synthesis of compound 78

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

• the biogenesis of this heterocyclisation leading to the pseudomonine biosynthesis [23]. The absolute configuration of the threonine residue in compounds 1 and 2 was assigned as ʟ, based on the derivatization of 1 and 2 hydrolysates with ʟ-FDAA, a Marfey’s reagent, followed by chromatographic profiling

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

• that this synthesis is easily scalable up to a 100 g scale. In the same year, Zhang et al. developed another highly modular route to 3,3-disubstituted oxetanes 173 via derivatization of oxetanyl trichloroacetimidates (Scheme 43) [95]. This method, inspired by a Schmidt glycosylation, provides easy

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

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• structure of pipecolic acid is rather challenging and often necessitates early-stage derivatization followed by the formation of the six-membered ring [29][30][31][32]. An alternative is to utilise derivatization reactions such as Suzuki–Miyaura [33] or Sonogashira–Hagihara [34] cross-coupling reactions on

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

• excellent yield (Scheme 2) [32]. The formed anhydride 3 was smoothly converted to the amide at room temperature. This method provides a green approach by allowing cinnamic acid derivatization in water as a benign solvent. Similarly, Rajendran and Rajan (2023) reported a one-pot transamidation of cinnamamide

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• excitation [66][67], product derivatization was explored (Scheme 2A). While initial efforts for oxidation proved challenging, due to a competing retro-aldol ring-opening reaction, employing a buffered system enabled access to β-alcohol 5. Given the previous power of trifluoroborates in cross-coupling

• cyclobutyldiol. A) Product derivatization and B) transition-metal EnT catalysis. Reaction conditions A): 4d (1 equiv), H2O2 (30 wt % in H2O), aq NaH2PO4, THF, 0 °C; B) 4 (1 equiv), KF (4 equiv), ʟ-tartaric acid (2.1 equiv), MeOH, MeCN, H2O, rt. Probing EnT catalysis of alkenylboronic ester 1a via alkene

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

• bromoalkyl HBC derivatives 7, 8, and 9. Synthesis of the HBC ether derivative 11. Derivatization of the HBC fluorophore 5 to generate handles with distinct electrophilic groups. Synthesis of mesylated HBC fluorophores 16, 17, and 18. Synthesis of the bifunctional HBC fluorophore 22. For an application of 22

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

• subsequent opening of the furanone ring and proton transfer results in final compounds 8, 10 and 11. The synthetic application of obtained pyrazolones 8 was demonstrated by its further derivatization. The interaction with electrophilic agents is determined by the presence of several nucleophilic centers in

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• [17]. As a starting point for further derivatization, the synthesis and characterization of monohalogenated N-acetyl diazocines 2 and 3 (Figure 1) have been performed [22]. Unfortunately, diazocines in general, and N-acetyl diazocines in particular cannot be derivatized by electrophilic aromatic

• substitution. Substituents such as halogen atoms must be introduced into the N-acetyl diazocine structure during the synthesis of the building blocks. In the present work we start from mono- and dihalogenated N-acetyl diazocine 2–4 (Figure 2) and focus on the further derivatization via cross-coupling reactions

• diazocine attached to glutamate to form a photoswitchable neurotransmitter [10]. The halogen-substituted N-acetyl diazocines 2–4 were used as the starting compounds for further derivatization via Pd-catalyzed cross-coupling reactions. Solutions of the Z isomers are yellow. The E isomers are red. Synthesis

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• further investigate the potential utility of this methodology, a gram scale experiment was conducted affording product 16f in a good yield and a slight decrease of the enantioselectivity. Additionally, a derivatization of product 16f by hydrogenation was carried out to yield the tricyclic piperidine 17

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• successful derivatization of sulfoxonium ylides with trifluoroethyl or tetrafluoropropyl groups, and provides valuable insights into the scope and limitations of this approach. Nineteen examples have been prepared (45–92% yields), with structural diversity modified at two key sites on the sulfoxonium ylide

• discovered by Umemoto has proven an effective electrophilic trifluoroethyl transfer reagent [34][35], and to further explore the potential of fluoroalkyliodonium salts we evaluated the reactivity of such compounds in the context of sulfoxonium ylide derivatization. As depicted in Table 1, we began our

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• accepting a wide variety of protective and functional groups, the method creates products with an iodine substituent that is easily accessible for product derivatization. Moreover, it is a convenient methodology for both N-arylation and O-arylation. The arylation of amines 38 was achieved in acetonitrile as

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• readily available and cheap. Since then, indigo was produced in large scale. The synthesis, derivatization, and application of indigo derivatives have been widely studied [1][2][3]. Besides their application as dyes, indigo derivatives represent versatile tools for the development of innovative

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• a tetrafluoroethylene group on an asymmetric carbon center. Synthetic strategy for preparing fluorine-containing amines via [1,3]-proton shift reactions. Preparation of the substrates used in this study. Derivatization of (S)-20b to (S)-23b for determining the optical purity of (S)-20b. Substrate