Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• -aminoazoles into the Biginelli reaction allows azolo[1,5-a]pyrimidines [10][11][12][13][14][15][16] to be synthesized, in general, the range of products obtained in these syntheses is predictable and limited. Ethyl trifluoroacetoacetate and its polyfluoroalkyl-containing analogues are also used widely as

• , respectively. The introduction of cycloketones has resulted in the same types of heterocyclic systems, yet they are now carboannelated, which are synthetic analogues of alkaloids [26]. Moreover, it has been shown that acetaldehyde is capable of reacting in a similar manner with ethyl trifluoroacetoacetate and

• in the piperidone ring shows upfield shifts (δF 79.50–79.61 ppm) compared with the cis-analogues 4a–dcc, 4a–dct (δF 79.92–80.09 ppm). The configurations of diastereomers 5ctc and 5ctt were established using XRD (Figure 3). Figure 5 shows a fragment of the 1H NMR spectra of hexahydrooxazolo[3,2-a

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• , respectively (Scheme 2). The structure of compounds 20e and 21g was also confirmed by single-crystal X-ray diffraction (Figure 3). We demonstrated the potential utility of the synthesized new ring systems in the field of medicinal chemistry by the synthesis of tetracyclic analogues 20b and 21b of tianeptine

• analogues 20b and 21b. Conditions: 20b: NaOH, EtOH/H2O, rt, 25 h, 80%; 21b: NaOH, EtOH/H2O, rt, 19 h, 73%. Synthesis of tetracyclic ethers 23 and thioether 24. Conditions: i) ROH, MeCN, rt, 2–3 h, 38–84%; ii) 2-(morpholin-4-yl)ethanethiol, MeCN, rt, 1 h, 72%. Synthesis of pentacyclic compounds 25–27

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

• leading not only to improved extraction effectivity but also to enhanced selectivity [2]. Anion extractants based on functionalized polystyrene or silica gel typically incorporate calixarenes [6] and their analogues, calixpyrroles [7][8], azacalixarene derivatives [9], or expanded porphyrin-like sapphyrin

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

• asymmetric reactions and are functional transformations in synthetic organic chemistry. Especially, 1,2,3-triazole-based NHCs are generally more reactive and stronger σ-donors than imidazole or thiazole analogues. Triazolium NHC enhances their ability to stabilize reactive radical intermediates or acyl anion

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

• platform for synthesizing other family members and their structural analogues. The synthetic sequence commenced with common intermediate 103 as the starting material. Stereoselective reduction of 103 yielded compound 111 as a single diastereomer. Systematic optimization of reaction conditions revealed that

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

• synthesis and structural determination of malaymycin A (1) as well as the subsequent design of structural analogues for biological evaluation [16][17][18][19][20]. Preliminary structure–activity relationship (SAR) studies revealed that fungicidal activity is highly dependent on the nature and

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

• 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

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

• in a stable aldehyde 23. This aldehyde is a product of intramolecular aldol–croton condensation and can be used in the synthesis of bartsioside (24) or its analogues [21][22] (Scheme 4). The authors [19] performed similar oxidative transformations with Diels–Alder adduct 25 obtained from LG and

• obtaining medically interesting dactylicapnosine-like analogues for detailed study of their biological activity. Matoba et al. [45] reported the first enantioselective synthesis of the hasubanane alkaloid (−)-metaphanine (70) and the norhasubanane alkaloid (+)-stephadiamine (71) using a cyclohexane ring

• rearrangement to lupane derivatives containing the betulin framework. This reaction was induced by a number of catalysts, including hydrogen chloride, montmorillonite K10, and boron trifluoride etherate. As a result, promising derivatives for the synthesis of ceanothic acid analogues were obtained [106][107

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

• using N-methyl,C-phenylnitrone and N-methylmaleimide [110]. Furthermore, although mono- and bifunctional N-methylnitrones exhibit higher cycloaddition reaction rates than their N-phenyl analogues, their impact on selectivity is diminished [111]. It is well established that nitrones prepared from

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

• Johannes Puschnig Martyn Jevric Ben W. Greatrex Faculty of Medicine and Health, University of New England, Armidale, NSW, 2351, Australia 10.3762/bjoc.21.175 Abstract Halogenated butyrolactones are found in a variety of bioactive materials and used for the construction of nucleoside analogues

• influenza [7], while chlorinated analogues such as 3 have demonstrated activity against hepatitis C (Figure 1) [8]. Stereoselective methods to access halogenated γ-butyrolactones are therefore valuable, as they enable access to nucleoside analogues which have applications in treating cancer and certain

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

• cyclopropanation of 1,6-enyne initiated a cascade involving 1,5-enyne addition, consecutive 1,2-alkyl migrations, and Friedel–Crafts alkylation, efficiently constructing the pentacyclic fused benzofuran framework 21 (Scheme 5, path b). Above two analogues were prepared on a gram scale, converted into valuable

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

• also evidenced by the better affinity for DYRK1A of the acidic molecules as compared to their ester analogues. Therefore, this new interaction could explain the higher affinity of VS-77 toward Hs_DYRK1A, as compared to DB-18. Conclusion In the present work, we disclosed a new strategy to improve the

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

• Paris, France 10.3762/bjoc.21.170 Abstract Azobenzenes are photoresponsive compounds widely used in molecular switches, light-controlled materials, and sensors, but despite extensive studies on symmetric derivatives, efficient methods for synthesizing non-symmetric analogues remain scarce due to

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

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

• ]. Given the presence of the indole moiety in indolo[1,2-c]quinazolin-6(5H)-one (1), the design of novel gramine-like analogues via aminomethyl substitution at position 12 is feasible. To evaluate the influence of the urea carbonyl group on biological activity, a modified scaffold, 6-methylindolo[1,2-c

• indolo[1,2-c]quinazoline framework, which enabled the generation of carboxamides, aminomethylated analogues using classical and advanced methodologies. Among these, 12-substituted aminomethyl derivatives exhibited the most promising antiproliferative activity, with compound 9c showing notable

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• natural products of the monocerin-family Early in 1979, monocerin and 7-O-demethylmonocerin were elucidated from Fusarium larvarum [20]. Since then, a large group of analogues have been isolated from diverse fungal species [21][22][23][24][25] (Scheme 2). Along with the structural elucidation, biological

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

• ring system with the appropriate functional groups in place for attaching the remaining groups is a highly important task for the asymmetric total synthesis of PGs and analogues [10][11][12][13]. The groups of Aggarwal [14], Hayashi [15], and Zhang [16] have reported bond-disconnection strategies for

• total synthesis of 4 and is required to explore alternative synthetic strategies for PGs and analogues [17]. Biosynthetically, 4 is proposed to arise via a 5-exo-trig biogenetic radical-mediated cyclization (Scheme 1C) [18][19]. Over the past five decades, the Snider oxidative radical reaction has been

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

Synthesis of chiral cyclohexane-linked bisimidazolines

• Changmeng Xi,
• Qingshan Sun and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140

• bisimidazoline (PyBim) ligands derived from pyridine-2,6-dicarbonitrile or pyridine-2,6-dicarboxylic acid and vicinal diamines, as analogues of pyridine-linked bisoxazoline (PyBOX) ligands [16][17]. They exhibited excellent performance in metal-catalyzed asymmetric organic reactions. Chiral rigid backbone-linked

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• to the preparation of triazaphospholes and triazaarsoles, π-conjugated species with potential applications in materials science due to their luminescent properties [98]. However, these heavier alkyne analogues are typically kinetically unstable, which limits their use as dipolarophiles. Despite that

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

• towards 5-mercapto-1H-tetrazoles was compared with well-known analogues derived from adamantanethione and 2,2,4,4-tetramethyl-3-thioxocyclobutanone. Some of the isolated thioaminals were observed to undergo thermal isomerization in CDCl3 solution yielding the corresponding dithioacetals. Structural

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• diterpenoids, including alterbrassicicene E and brassicicenes A and R in 4 or 5 chemical steps from brassicicene I. This strategy lays the foundation for the preparation of fusicoccane diterpenoids and their analogues for biological studies. Keywords: cotylenol; fusicoccane diterpenoids; heterologous

• ][23][24][25][26]. Most of these synthetic approaches rely on similar strategies, i.e., coupling of the A ring and the C ring followed by the formation of the B ring. Additionally, the semisynthesis of analogues of 1 has been reported and led to the discovery of ISIR-050 (4), which shows higher

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• isonitrile remained when only 1 equivalent was employed. The limited scope of iodonium salts for arylations usually arose from the poor range of synthetically accessible symmetrical salts compared to their unsymmetrical analogues. However, the selective transfer of one of the aryl groups is a main challenge

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

• length. Protonation further induced red-shifted emission, with compound 14d-H+ emitting at 542 nm. However, PLQYs decreased significantly from 0.078 to 0.006 with longer helicenes. The CD spectra of 14c and 14d were found to resemble their carbohelicene analogues, underscoring the structural fidelity and

• conjugated systems, enabling the design of donor–acceptor helicenes with tunable photophysical properties. In 2020, Ema and co-workers developed a series of chiral carbazole-based BODIPY analogues 35a–f, derived from helical carbazole-based BF2 dyes [49] (Table 11). These analogues exhibit red-shifted

• -workers introduced various boryl substituents at both termini of a series of nitrogen-doped [5]helicenes, yielding helicenoids 42a–h [57] (Table 14). The Bpin-substituted derivatives 42a–e exhibited broad emission across the 400–800 nm range, whereas their analogues 42f and 42g showed negligible emission

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

• siderophores because the isolates share common structural scaffold and are analogues of previously confirmed siderophores, including pseudomonine and salicylic acid [26][27][28] which were also isolated from the same culture as well. The experimental work to confirm these types of compounds as siderophores was