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

• that the diarylmethine stereocenter at C7′ in 6 could be formed by an Evans’ auxiliary-induced asymmetric conjugate addition of α,β-unsaturated acyl oxazolidinone 7 with 3,4,5-trimethoxyphenylmagnesium bromide (8). Both of these two building blocks could be conveniently prepared from commercially

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• chemotherapy and achieving targeted treatments [18][19][20]. In the era of nanotechnology, a promising strategy for developing more effective treatments against cancer [21][22], calixarene derivatives are also emerging as valid building blocks for the development of nanoscale multivalent constructs [23]. Due

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

• robust approach to a wide range of 3-substituted thiophene-2,5-dicarboxylates. These intermediates are of interest as valuable building blocks for the synthesis of more complex thiophene derivatives in both materials and medicinal chemistry contexts. The synthetic routes to 3-hydroxy-substituted TT

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• involves a formal 1,3-C shift. Keywords: Aspidosperma alkaloids; [2 + 2]-cycloaddition/retro-Mannich reaction; DFT study; photoinduced electron transfer; Introduction Photochemical reactions, which enable the construction of topologically complex architectures from simple building blocks, have attracted

• valuable strategy for synthesizing natural and unnatural products from simple building blocks [4]. Three distinct photoinitiated approaches have been established for the formation of the [2 + 2] cycloadducts: direct irradiation [5][6], energy transfer (EnT) [7], and photoinduced electron transfer (PET, or

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

• used building blocks in glycosylations. For the synthesis chamber (A) was loaded with trifluoroacetamide (6 equiv) in pyridine. In the other chamber (B), the hemiacetal (ca. 500 mg, 1 equiv) was dissolved in CH2Cl2 together with a catalytic amount of DBU. Upon addition of trifluoroacetic anhydride

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• development of a new methodology for the synthesis of galactofuranoside building blocks, we encountered an unexpected predominance of the furanoside form in the equilibrium mixture of benzoylated β-galactosides. Since the furanoside form is typically less stable and is usually present only in minor amounts

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

• aldol condensation of the resulting dialdehyde. This strategy is widely used at the key stage in the formation of a cyclopentane ring in the synthesis of various building blocks, including echinopine A (3) [10][11][12] (Scheme 1). The ozonolysis–cyclization sequence was used by Alvarez-Manzaneda et al

• simple building blocks [72]. The main feature of light-induced transformations is the involvement of electronically excited states that occur during photon absorption, leading to the formation of reactive intermediates causing significant changes in chemical compound reactivity. As a result, light energy

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

• protection as ketal and nitrile reduction. The two building blocks (76 and 81) were then merged through the desired formal [3 + 3]-cycloaddition to generate N-desmethyl-α-obscurine (82), presumably via in situ-generated intermediates 76a and 81a, respectively. Subsequent Boc protection of the cyclic amine in

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 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

• The desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds is a powerful tool for the construction of ring systems bearing multiple stereocenters including all-carbon quaternary stereocenters, which are widely useful chiral building blocks for the total synthesis of structurally

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

• quinoxalinones and Ugi reaction products may be valuable for organic synthesis and medicinal chemistry because the presence of a free carboxyl group makes them promising for use as building blocks for the construction of complex heterocyclic structures, including those using multicomponent reactions. Some

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

• synthesis of strained compounds such as bicyclo[1.1.0]butane (BCB) and bicyclo[2.1.0]pentane (housane). The energy stored in strained σCC bonds of BCB and housane makes them important building blocks in the synthesis of complex molecular structures. BCBs have been employed in ring-opening reactions with

• nucleophiles [7][8][9][10][11], radicals [12][13][14][15] and electrophiles [16][17][18] to give cyclobutanes and cyclobutenes [19][20], which are building blocks in regio- and stereoselective synthesis [21][22][23][24][25][26][27] (Scheme 1a). Additionally, BCB has been used in bioconjugation due to its high

• mechanical calculations and NAMD simulations to investigate the mechanism of photodenitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives, which produce the strained compound housane, important building blocks in the synthesis of complex molecular structures. We identified that the key

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

• acetylation of prochiral 1,3-diols to access chiral building blocks (R)-3 and (R)-11, Shishido's team completed a series of helianane-type sesquiterpenes. This pioneering work demonstrates the utility of prochiral 1,3-diols in the synthesis of natural products. In 2013, the first asymmetric synthesis of the

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

• . Remarkably, the synthetic approach was compatible with building blocks bearing three different S(VI) warheads, enabling the direct connective synthesis of diverse reactive probes armed with non-cysteine-directed warheads. Reactive probes that are synthetically accessible using our approach may be of value in

• 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

• activity against T. brucei, a parasitic kinetoplastid that causes vector-borne African trypanosomiasis, and four probes with promising anti-trypanosomal activity were identified. Remarkably, the synthetic approach was compatible with building blocks bearing three different S(VI) warheads, and enabled the

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

• leveraging the synthesized enantioenriched aza[6]helicene 29a and tetrahydro[6]helicene 30a as chiral building blocks, a series of helically chiral organocatalysts and ligands could be easily prepared, such as the helically chiral pyridine N-oxide 31a and helically chiral monophosphine ligands 31b,c, whose

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• production of approximately 30 million tons annually [40]. Their low cost and widespread availability make them highly valuable as fundamental building blocks in organic synthesis. Over the past few decades, the direct functionalization of styrenes has emerged as a prominent research area due to its

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

• photo-responsive cages or capsules include fabricating cages and capsules from photoactive building blocks, and developing cages and capsules encapsulating photo-responsive guest molecules [112][113]. Incorporating supramolecular amphiphiles into photo-sensitized systems has propelled the creation of

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• ][17][18][19][20][21][22][23] and more [24]. Especially BINOL-based crown ethers proved to be highly useful and were applied for stereoselective molecular recognition [25][26][27], for catalysis [25][28][29][30][31], as stationary phases for chromatography [32][33][34], but also as building blocks for

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

• typically exist as a mixture of anomers which complicates their use in the chemical glycosylation reactions. Earlier approaches to constructing 1,1'-O-glycosidic bonds often relied on the use of simply and symmetrically protected (benzylated or acetylated) monosaccharide building blocks, enabling the

• 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

• this shortcoming, it is essential to use monosaccharide building blocks bearing temporary protecting groups that can be selectively and sequentially removed under mild conditions. Such an approach ensures compatibility with sensitive functionalities and enables the effective incorporation of 1,1

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

• become a hot topic in synthetic organic chemistry. Isocyanides (also termed isonitriles) are a class of highly versatile building blocks in organic synthesis, participating in a wide range of transformations including multicomponent reactions (e.g., the well-known Passerini and Ugi reactions) [13][14][15

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• reaction, in which 2H-azirines act as the annulation reagent. Keywords: annulation; azirines; benzothiophenes; indoles; nickel catalysis; Introduction 2H-Azirines represent a valuable class of nitrogen heterocycles that are widely used as versatile building blocks in organic synthesis. In particular, the

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

• precluded the potential issues inherent to one-pot glycosylation based on thioglycosides such as aglycone transfer [43][44][45][61]. Results and Discussion Retrosynthetic analysis Retrosynthetically, we envisaged that glycans 1–4 could be derived from monosaccharide building blocks Man PTFAI 5 and 6, Man

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• act as both electrophiles and nucleophiles [7]. This makes enaminones very reactive, providing an excellent scaffold for organic synthesis. Thus, enaminones are valuable building blocks in the preparation of several carbocyclic [8][9][10][11], heterocyclic [12][13][14][15][16][17][18] as well as

Azobenzene protonation as a tool for temperature sensing

• Antti Siiskonen,
• Sami Vesamäki and
• Arri Priimagi

Beilstein J. Org. Chem. 2025, 21, 1528–1534, doi:10.3762/bjoc.21.115

• emerged as staple building blocks in smart materials, from light-responsive norbornadienes in molecular solar thermal energy storage [2] to pH-sensitive spiropyrans in cell imaging [3], and redox-active viologens in memory junctions [4]. Among the different molecular switches azobenzenes stand out due to

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• ]-cycloaddition of respective thiocarbonyl dipolarophiles (preferably non-enolizable thioketones) with diazomethane, was demonstrated as a favorable method for their generation [5][6]. In the past three decades, 1,3-dipoles 1 have extensively been studied as useful building blocks for the preparation of various

• hindered) suggests that the steric hindrance can play an important role in the trapping process. It is worth of emphasizing that thioaminals [33] and dithioacetals [34] constitute important groups of building blocks, which are of interest not only for pharmaceutically oriented studies [35] but also for