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

• a hot topic [75]. PAs can be prepared via the Friedel–Crafts condensation, which involves combining 1,4-dimethoxybenzene with paraformaldehyde in the presence of a Lewis acid. The central axis of these aromatic hydrocarbon molecules possesses n fold rotational symmetry [76]. PAs possess highly

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• DCC-induced condensation of phenylacetic acid reported by Bhandari and Ray [22] and others [23][24][25][26][27]. Initially, we converted indole-3-acetic acid to its methyl ester, followed by protection of the indole nitrogen with a Boc group and subsequent hydrolysis of the methyl ester to regenerate

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

• were readily prepared by self-condensation of the corresponding acetylated methyl 1,2-orthoacetates using BF3·OEt2 as a promoter [55]. While the 1,2-orthoester functionality in the glycosyl donor 17 directed the 1,2-trans selectivity towards the formation of an α-mannosidic linkage, the anomeric β

• due to the strong electron-withdrawing effect of the picolinium substituent, effectively preventing anomerization or self-condensation. Good stereoselectivity and yields were achieved in the glycosylation reactions of 4-O-picoloyl-protected TMS-α-glycoside acceptors with stereodirecting thioglycoside

• derivatives 130 and 131, respectively [63]. A separate case of obtaining symmetric 1,1-disaccharides of the manno- and talo-series 133 and 135, respectively, via self-condensation of the corresponding 3,4,6-tri-O-benzylated 2-iodolactols 132 and 134, has also been reported (Scheme 11) [115]. In specific cases

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

• condensation between 27 and the aldehyde afforded INT-A, which was activated by the CPA catalyst through hydrogen bonding interaction. The nucleophilic addition of isocyanide to Int-A produced INT-B bearing a stereogenic center. Subsequently, INT-B underwent intramolecular cyclization to generate axially

• functionality in 63 allowed for versatile derivatizations, such as reduction, reductive amination, condensation, and olefination, which further expanded the structural diversity of the resulting products. Summary and Outlook The past few years have witnessed exciting progress in developing catalytic asymmetric

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• successfully introduced into homogeneous [26][27][28][29] and heterogeneous [30][31] carbon–carbon and carbon–heteroatom bond-forming protocols. Although its reactive carbonyl group could limit its application when a strong base (aldol condensation [29]) or amines (potential Schiff-base formation) are present

• , a wide range of organic reactions, e.g., urea and amide formation [32][33], amide coupling [34], aldol condensation [35], C–H difluoromethylation [36], aromatic substitution [37], and MOFs synthesis [38] were demonstrated in CyreneTM. Very recently, Fasano and Citarella first reported a CuAAC

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

• condensation of 1,3-dicarbonyl compounds with amines [30]. While this approach is simple and straightforward, it often leads to a mixture of constitutional isomers in which the two different α-positions of the ketone have been functionalized. Therefore, the development of novel methods for the synthesis of

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

• condensation product, compound 2. Compound 1 is proposed to further undergo a dehydration reaction by the elimination of the α-proton and β-hydroxy group of the threonine residue to form compound 3. Compound 4 is a product of methylation of 3 carboxyl functionality (see Figure 4). These compounds are possibly

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• of catalyst- and solvent-free processes is desirable. Chalcones are a privileged scaffold in medicinal chemistry and are used for the synthesis of a multitude of products [43]. The cyclization between chalcones and hydrazines usually occur via a C=O/NH2 condensation and a subsequent NH addition to

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• by Jutz and Kirchlechner in 1966 (Scheme 3) [36]. Condensation between phenalene 15 and pentafulvene 16 gave pentafulvene 17. Pentafulvene 17 was finally subjected to Ziegler–Hafner reaction in quinoline at 180 °C, resulting in the π-extended azulene 18 in 60% yield. A similar synthetic strategy was

• -like electronic structure. Liu and co-workers developed a modular approach to for synthesizing azulene-embedded isomers of linear acenes (Scheme 11) [59]. Precursors 67–70 were obtained from aldehydes and substituted cyclopentadienes using Knoevenagel-type condensation. Finally, intramolecular

• palladium-catalyzed C–H arylation afforded the fused azulene-embedded PAHs 71–74 in good yields (40–70%). All non-alternant isomers of linear acenes exhibit azulene-like lowest energy optical absorption, attributed to the azulene-like S₀→S₁ transition. Condensation reactions: Various condensation reactions

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• Julius Krenzer Thomas J. J. Muller Heinrich-Heine-Universität Düsseldorf, Institut für Organische Chemie und Makromolekulare Chemie, Universitätsstraße 1, D-40225 Düsseldorf, Germany 10.3762/bjoc.21.97 Abstract Aroyl-S,N-ketene acetals are obtained by condensation of aroyl chlorides and 2-methyl

• ; condensation; Einhorn-type acylation; 2-methyl N-benzyl benzothiazolium salts; Introduction Aroyl-S,N-ketene acetals, in particular N-benzyl derivatives 1, are very short donor–acceptor chromophores that have recently found a renaissance due to their peculiar intense solid-state emission and significant turn

• 1 suggests starting from aroyl chlorides 2 and 2-methyl-N-benzylbenzothiazolium salts 3 by a condensation transform (Scheme 1). The condensation essentially represents an addition–elimination sequence that starts with the nucleophilic S,N-ketene acetal 4, in situ generated from substrate 3 by

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• followed by acid-mediated condensation. The linear copolymers show good solubility and carbon dioxide adsorption. Keywords: alternating copolymer; building block; formylation; gas adsorption; propellane; Introduction Combination of sp2- and sp3-hybridized atoms in core π-skeletons [1][2][3] is a key to

• well with the observed reactivities and selectivity. Attempted macrocyclization leading to linear polymers Formyl groups have diverse reactivities and enable facile condensation, dynamic covalent chemistry, and so on. In this work, we tried the synthesis of cyclic oligomers composed of naphthalene

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• approach for constructing Morken’s C2–C12 fragment In 2019, Uguen and co-workers introduced a strategy to assemble Morken’s C2–C12 intermediate 20 [41]. Their approach utilized iterative base-catalyzed condensation of sulfone compounds with epoxides. As illustrated in Scheme 1, the monoalcohol 20 was

• prepared via PMB removal of compound 21, which, in turn, was obtained through desulfonylation of compound 22. Compound 22 originated from the condensation of epoxide 23a with sulfone 26, which was produced by desilylation of 25 followed by converting the resulting primary alcohol into a sulfone group

• . Intermediate 25 was prepared through TBDMS protection and desulfonylation of 24, itself derived from the condensation of epoxide 23b and sulfone 27. The precursor 27 was synthesized from Roche ester 29 via a sequence of steps, including reduction, three-carbon homologation, and enzymatic desymmetrization. An

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• [5] and the FDA-approved antibiotic linezolid [6] (Figure 1). Both chiral oxazolidines [7][8] and oxazolidinones [9][10] have been utilized as chiral auxiliary groups in many asymmetric organic transformations. Oxazolidine derivatives have been prepared mainly from condensation of vicinal amino

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

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• aldol condensation of 5 provided the tetracyclic α,β-unsaturated enone 6 in 57% yield. Subsequent catalytic hydrogenation using Pd/C conditions delivered the hydrogen to the alkene from the less hindered face, producing ketone 7 with high diastereoselectivity. Final reduction of both the amide and

• intermediate would meet challenges associated with the instability of enolate derivatives. In their recent study, they successfully developed such a polycyclization taking advantage of a novel spiropyrroline-derived oxazole (SPDO) ligand (L3). As shown in Scheme 7, one-pot condensation of primary amine 40, β

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• hydrogenation of the C=C double bond in the side chain gave brevicarine (2). The first total synthesis of brevicarine is shown in Scheme 3 [2][20][21]. Condensation of indole (11) with 1-methylpiperidone (12) gave compound 13 [22]. N-Alkylation of 13 with benzyl bromide, followed by treatment of the quaternary

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• essential tertiary alcohol at C1. The β-hydroxylactone moiety (D ring) in 11 could be introduced through an intramolecular aldol condensation [35] of acetate 12. Ultimately, the preparation of 12 could be traced back to aldehyde 14 through 1,2-Grignard addition with an organomagnesium reagent [36] prepared

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• intramolecular condensation with the arylglyoxal-derived keto-carbonyl group [37]. In 2024, the same group streamlined this strategy by utilizing unprotected anthranilic acids, enabling the assembly of benzo[e][1,4]diazepines 6 directly during the Ugi reaction step [38]. In 2013, Van der Eycken and co-workers

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• structurally diverse macrocycles through the dynamic self-assembly of α,α’-linked oligopyrrolic dialdehydes and alkyldiamines (Scheme 10) [39]. Their investigation revealed distinct solvent-mediated selectivity in product formation. Condensation of the pyridine-bridged oligopyrrolic dialdehyde 37 with simple

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• single-crystal X-ray diffraction [19]. According to a previous publication, the condensation between pyrrolidine-2,3-diones and an amine as nucleophile normally occurred at the 3-position of nitrogen-containing heterocyclic ring which results in the corresponding enamine product [18]. However, the

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

• nucleophilic aromatic substitution of 4-fluorobenzaldehyde with 2-(methylamino)ethanol, 3-methylamino-1-propanol or 2-[2-(methylamino)ethoxy]ethan-1-ol in the presence of potassium carbonate to afford benzaldehyde derivatives 1, 2, and 3 in excellent yields. Next, the piperidine-induced condensation with 4

• monitored by the inherent fluorescent signal of the target RNA [11]. The synthetic route to such an HBC fluorophore is shown in Scheme 6. Piperidine-induced condensation of compound 2 with 4-iodophenylacetonitrile afforded the HBC-like ligand, whose hydroxy group was immediately protected with TBS-Cl to

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

• of chemoselectivity becomes important when formaldehyde is used. Moreover, primary amines (alkyl- and arylamines) can also react with two equivalents of both the formaldehyde and the P(O)H compound. In this case, a double Kabachnik–Fields condensation gives bis(phosphorylmethyl)amines 34 as possible

• (Scheme 30). As glyoxylates are C2 structures, their use as C1 building blocks in MCRs instead of formaldehyde, requires an extra path, usually a decarboxylation process, after the condensation reaction. However, by appropriately choosing the glyoxylate derivatives (for example, ethyl glyoxylate), post

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

• with diverse N-nucleophiles was investigated. It was shown that the direction of the process depends on the type of employed nitrogen-containing reagent. For example, condensation with aliphatic amines leads to 2H-furo[3,2-b]pyran-2,7(3H)-diones bearing an exocyclic enamine moiety. At the same time

• under various conditions. Initially, we performed the studied process with equivalent amounts of starting materials in ethanol at reflux for 1 h. As a result, no products of condensation or recyclization have been obtained. At the same time, stable salt 3a was isolated in 95% yield (Scheme 2a). Besides

• ). Apparently, for the realization of the presented condensation, the nucleophilicity of the aromatic amines is not sufficient. Wherein, the type of substituent in the aroyl fragment of furanone 1 doesn’t influence the result of this reaction. Thus, enamines 4 can be synthesized only using active aliphatic

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• ). As shown in Scheme 2, in the initial step, the aldol condensation of 2,3,3-trimethylindolenine 2 with o-chloranil (3) leads to the intermediate compounds, 6-(2-hetarylmethylene)-6-hydroxy-2,4-cyclohexadien-1-ones 4. Such intermediates were isolated preparatively and structurally characterized in the

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• generate crotonic condensation adducts of active methylene compounds and formaldehyde at room temperature in the absence of strong acids and bases. The formed adducts were highly reactive intermediates capable of reacting with dienes in a three-component reaction, leading to the formation of Diels–Alder

• main reaction products. Keywords: aldol condensation; [4 + 2]-cycloaddition; diffusion mixing; formaldehyde; Knoevenagel condensation; three-component reactions; Introduction Formaldehyde is a reactive electrophilic reagent widely used as a C1 building block in multicomponent reactions [1][2][3]. Its

• role in most cases is to generate highly reactive species in situ from the nucleophilic reaction component. This can subsequently interact with other reaction components to form target products. Compared to the crotonic condensation products of other aliphatic and aromatic aldehydes, methylidene