Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• reactions [10]. Oxidation of the alcohol is done in situ to avoid problems regarding the isolation and instability of the aldehyde produced, although undesirable reactions, such as oxidation of the amines or isocyanides or overoxidation of the alcohol, could also be problematic [11][12]. In this regard

• well for a wide variety of solvents and under mild basic conditions, since the solubility of the reagents and ease of product isolation are the factors that govern the choice. Sisko et al. used DMF/K2CO3 as the best conditions to carry out the cycloaddition of a wide variety of amines, aldehydes, and

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

• isolation of intermediate salt 3a. Indeed, the reflux of starting compound 1a with amine 2a in AcOH for 24 h led to formation of product 4a with 62% yield. Using various furanones 1 and amines we attempted to synthesize analogues of compound 4a based on the above procedure. It was found that the presence of

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• isolation from cyanobacteria [2], their extraordinarily high cytotoxicity was apparent and attracted attention, not least because of their still high efficacy against multidrug-resistant (MDR) cells [3]. Cryptophycin-52, a synthetic development candidate by Eli Lilly based on the initially discovered

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• ANTH and the –C6F5 group might provide the desired spatial isolation of the ANTH (and other PAH) cores, and result in enhanced photoluminescence by disrupting close π–π stacking in the solid state. In addition, air- and photostability might also be improved due to the steric and electronic properties

• a relatively fast and efficient conversion into the desired products. Further optimization of this promising photochemical method is currently under way in our laboratory. Isolation and characterization Pure samples of 9,10-ANTH(BnF)2 and 9-ANTH(BnF) were isolated by HPLC (Figure S3, Supporting

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

• yield (94%). The reaction remained efficient across a variety of substrates, as shown in Scheme 3. The authors noted that, if the mixture was not ground before irradiation, product 3.3 was obtained in just 46% yield after isolation. Thus, the role of mechanochemistry was to achieve optimal mixing of the

• ]. As an example, the authors were able to convert 4,4’-dimethoxybenzhydrol (6.1) to 4,4’-dimethoxybenzophenone (6.2) in 74% yield after isolation using 5 mol % RFTA under air (24 h), all performed without any additional solvent (Scheme 6). The authors noted that the reaction proceeds via a molten state

• oxidation of 1,2-diphenylethyne to benzil [71]. Thus, when a 1:2 mixture of 7.1 and 4-chlorothiophenol (7.2) was ground in the presence of eosin Y as the photocatalyst and anhydrous Na2SO4 as a bulking agent, benzil (7.3) was obtained in 43% GC yield under blue light irradiation (LED, 14.5 W). Isolation led

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

• , sometimes under the moniker “enzyme mimic” [22][138]. MOCs are typically soluble in polar organic solvents or water [156][157], and so their dynamics can be studied using solution-phase techniques [22]. Isolation from solution is not always possible, since their dynamic nature can make them sensitive to

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• isolation of any trace of β-product (Scheme 12). Based on the same concept and stabilisation of the intermediate α-triflate by the participation of the 2-O-protection group in glycosyl donors, Yamago et al. illustrated the use of dialkyl phosphates as the 2-O-protecting group (compound 75 in Scheme 13) for

• the formation of 1,2-trans stereodirected glycosyl products 77 when the donor was suitably activated using BSP and Tf2O [139]. The role of the 2,2-dimethyltrimethylene (DMTM) phosphate group at the participating C-2 protection was analysed wherein the NMR studies showed no isolation of the

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• [6], which has to the best of our knowledge not been studied before on its secondary metabolism. The current study deals with the isolation and characterization of the major bioactive principles of the ex-holotype strain of Samsoniella aurantia. Results and Discussion Structure elucidation Compound 1

• evaporation at 40 °C, forming a semi-solid residue dispersed in water. Liquid–liquid extraction against EtOAc (1:1) was conducted twice. The organic phases were combined, filtered, and evaporated under vacuum, while the aqueous phase was discarded. Isolation of compounds 1–6 The obtained organic crude extract

• ), a gradient elution was implemented, starting from 60% B and progressing to 100% B in 30 minutes. The gradient was then held at 100% B for 10 minutes, resulting in the isolation of 6 (30 mg, tR = 34 min). For the purification of fraction 4 (306 mg), a gradient elution was applied, transitioning

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• -hydroxyacetophenone and N,N-dimethylformamide dimethyl acetal (DMF-DMA) were reacted at 120 °C to give compound 3a, and without further isolation and purification, 1a, H2SO4 and TBAI were added directly to the reaction solution and the reaction was continued at 120 °C for 12 hours. In this way, the product 4a could

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

• Information File 1, Figure S2 [57], and the benzylic position on the THIQ ring [58]. Indeed, termination of the reaction just after 90 minutes instead of 20 h resulted in the isolation of the fluorescent intermediate 18 in 55% yield (Scheme S1, Supporting Information File 1). Even with the use of both

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• was crucial for the formation of the organozinc reagent (Scheme 19) [36]. Spiro-2,3-dihydroquinazolinones 26 were formed exploiting a one-pot multicomponent reaction, using isatoic anhydride, ketones and primary amines. The isolation of the amide intermediate XXIII obtained by the copper-catalyzed

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• substituted β-nitrostyrenes. This one-pot procedure allows the quick isolation of substituted β-nitrostyrene scaffolds with 62–83% yield under mild conditions, without the need for special precautions, inert atmosphere, and time-consuming purification techniques. Keywords: 2C-X; CuCl2; NaBH4; β-nitrostyrene

• suspensions and precipitation of the starting materials, make these solvents unsuitable for this reaction and the isolation of the products troublesome. The use of 2-propanol/water (2:1), together with the application of heat, ensures optimal solubility of the species involved. Moreover, the workup procedure

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• , differing from established isolation and separation techniques, holds the promise of not only enhancing the efficiency of HTE flow synthesis but also paving the way for more sustainable growth in this research area. Autonomous self-optimizing flow reactors Autonomous self-optimizing flow reactors (ASFRs

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• from the simultaneous formation of sulfinamide 6ea also isolated in this reaction for the first time (both in trace amounts). Reaction mechanism The inability to detect sulfinamide 6 and the isolation of sulfonamide 5, along with other byproducts (3, 4, and 7), stimulated us to propose a plausible

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• discovery of an additional psammaplysin derivative, ceratinadin G (1) (Figure 1). This paper details the isolation, structural elucidation, and biological activity of compound 1. Results and Discussion The marine sponge Pseudoceratina sp., collected in Okinawa, Japan, was initially extracted with MeOH

• ), as well as additional signals not matching those of any known psammaplysin derivatives. Further separation of this fraction using C18 HPLC led to the isolation of ceratinadin G (1, 0.4 mg, 3.2 × 10−4%) along with psammaplysin F (2) [10][11][12]. Ceratinadin G (1) was isolated as an optically active

• 49.8 ppm were used as internal references. Mass spectra were acquired on a JEOL JMS-T100LP spectrometer. Flash column chromatography was performed using a Biotage Isolera flash purification system. Extraction and isolation The EtOAc-soluble material (2.45 g) of the methanol extract (38.06 g) from the

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• aeruginosa biofilm inhibitors and antibiotic enhancers. Large-scale extraction and isolation studies resulted in the discovery of four new and minor natural products, ianthelliformisamines D–G (4–7) and the known steroid, aplysterol (8). Compounds 4–7 were fully characterised following 1D/2D NMR, MS and UV

• describe the large-scale extraction, isolation, and structure elucidation of four new metabolites, ianthelliformisamines D–G (4–7). Additionally, we report the isolation of the known natural products, aplysterol (8) and ianthelliformisamines A–C (1–3). Owing to the novelty of ianthelliformisamine D (4) we

• HPLC (RP-HPLC), which led to the purification of the known metabolites, ianthelliformisamines A–C (1–3) [7] and aplysterol (8) [13], and four new natural products, ianthelliformisamines D–G (4–7) (Figure 1). This extraction and isolation process was repeated twice to obtain sufficient quantities of the

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• studies, we employed benzaldehyde derivatives with various stereoelectronic decoration, excluding aliphatic ones due to their decreased reactivity resulting in failures to proceed [24][25][26][27]. Commercially available isocyanides utilized were cyclohexyl and tert-butyl isocyanide. Notably, an isolation

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• . Fractionation is an iterative process guided by screening for the desired bioactivity until the isolation of a pure compound. This workflow was invented by Selman Waksman and has facilitated the identification of the vast majority of natural products known to date. However, it has fallen out of favor due to

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• . A size-complementary rotaxane contains axle-end groups that are as large as the wheel cavity. Thus, it is sufficiently stable for isolation under ambient conditions, although a certain stimulus, e.g., heat or the addition of a base, can induce the deslipping reaction to degrade itself as each

• reaction confirmed that the deslipping of [3]rotaxane 3 was approximately 10 times faster than that of [2]rotaxane 6, offering a local maximum of the yield of [2]rotaxane species in the developing process (approximately 80% by the theoretical calculation) and enabling the isolation of [2]rotaxane during

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• , see Scheme 1). In order to break the symmetry and to generate the acid function only on one side, benzyl protection was performed. From diols 1, 2, and 3 statistical mixtures of unprotected, mono-, and di-protected products were obtained, from which the isolation of the desired mono-protected products

• bicarbonate (NaHCO₃) provided acids 7, 8, and 9. A byproduct is obtained during oxidation and it is assumed that this is the molecule oxidized at the benzyl position (see Supporting Information File 1, compounds 35–40). Work-up and isolation proved to be difficult, and therefore, the acids were directly

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

• the reaction to proceed under gentle conditions. This prevents the subsequent transformation of the obtained S-aryl xanthates, thereby facilitating their isolation with satisfactory to excellent yields. During the assessment of the reaction's versatility, first variously substituted (4-anisyl)(aryl

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

• material in Europe (Scheme 1). It is obtained by extraction and isolation of the colorless indole-O-glycoside indicane which is then hydrolyzed to give indoxyl. The latter undergoes oxidative dimerization to provide indigo. In the 19th century, syntheses of indigo were developed which made the pigment

• , indirubin, and isoindigo which can be regarded as blue, red, and yellow sugars, respectively. Review Indigo-N-glycosides (blue sugars) In 2002, Laatsch and Maskey reported the isolation of the akashins A, B and C, indigo-N-glycosides, from terrestric Streptomyces (Scheme 2) [17][18]. These natural products

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

•  3) [13][14]. To a dry THF solution of adduct 4a, butyllithium was added, and the reaction mixture was stirred at −78 °C for 5 min. Following the addition of acetic acid, the reaction mixture was concentrated and subjected to silica gel column chromatography, resulting in the isolation of ethyl 5

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• ketones reacted well too. Accordingly, 3j was obtained in 42% yield. Enone 1k gave 3k in 51% yield, and after isolation by column chromatography the product was obtained in 13% yield. Difluoromethyl enol ether 3l was formed from diketone 1l in 25% yield. Finally, conversions of the two cyclic ketones 1m

Young investigators in natural products chemistry, biosynthesis, and enzymology

• Jeffrey D. Rudolf,
• Lena Barra and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 2720–2721, doi:10.3762/bjoc.20.229

• , Japan 10.3762/bjoc.20.229 There is just something about natural products. When staring at these structurally complex molecules produced by diverse organisms on our planet, one may wonder why a particular natural product is made, how it is made, how I can make it, or how I can use it. The isolation and