Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• . Soon after, Shibata and co-workers developed a cycloisomerization strategy that generated various axially chiral polycyclic aromatic hydrocarbons (PAHs) 70 through bond-cleavage followed by successive cyclization reactions with excellent yields and enantioselectivity (Scheme 19) [58]. In 2020, Miller

• biaryl compounds. Highly enantioselective C–H arylation of heteroarenes. Synthesis of novel axially chiral N-arylcarbazole skeletons by the assembly of azidonaphthalenes and carbazoles through chiral phosphoric acid catalysis. Catalytic enantioselective synthesis of axially chiral polycyclic aromatic

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• ; electrochemistry; emission; helical elongation; helicene; photophysical; Introduction Chirality is a pervasive feature of natural and artificial systems, and chiral small molecules continue to underpin advances in chemistry and materials science [1][2]. Among them, helicenes – ortho-condensed polycyclic aromatic

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• , Novosibirsk, 630090, Russia 10.3762/bjoc.22.22 Abstract Rotational correlation time is a key parameter for organic radical contrast agents (ORCA) for magnetic resonance imaging (MRI). Design of polycyclic systems with incorporated nitroxide moieties in which rotation of the radical separately from the

• rotation of the radical separately from the framework is impossible could be particularly promising. Rigid polycyclic fused systems with incorporated nitroxide moieties could be one of the possible ways to achieve the above feature. We recently found that the reaction of sterically hindered 3-hydroxymethyl

• often leads to formation of complex polycyclic systems [17][18][19]. In this study, we aimed to construct rigid tricyclic condensed systems with an integrated nitroxyl radical fragment from 3-substituted 2-ethynylpyrrolidine-1-oxyls. The desired tricyclic nitroxides were prepared via intramolecular

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• biosynthesis, when the oxidation state of the terpenoids is being adjusted [28][29][30][31][32][33][34][35][36]. Starting with an already substantial number of these common polycyclic frameworks and adding the almost unlimited variability for oxidative enzymatic C–H functionalisation, it is not surprising that

• such as jolkinol C (45), the formation of complex polycyclic tiglianes and ingenanes is also invoked, even though detailed studies have still not been performed [111][112]. The required C-8→C-14 cyclisation would require a C-nucleophile to be present at C-14 (next to the cyclopropyl group), attacking

• 1,2-alkyl migration is invoked, giving rise to the bridged polycyclic system of 68. Apart from these larger classes of sesquiterpenoids there are many singular examples of rearranged and ring-size-modified kaurene derivates, such as pierisketone B (69) and pierisketolide A (70). These 7,5,6,5-systems

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• 10.3762/bjoc.22.20 Abstract Polycyclic spirobarbiturates containing a pyrrolizidine moiety were synthesized via a one-pot three-component 1,3-dipolar cycloaddition reaction of alloxan, ʟ-proline and N-substituted maleimides. The reaction stereoselectivity was found to depend on the nature of substituents

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• hydrogenation of the polycyclic aromatic compound PyBQ to PyBTHQ using this catalyst in HFIP (Scheme 5) [50]. Under the optimized conditions, only the heteroaromatic part of quinoline was reduced selectively, while the benzene ring and pyridine remained unchanged. In 2020, Beller and co-workers used a manganese

• functional group management can decisively shape the success of complex molecule synthesis. Total synthesis of jorunnamycin A and jorumycin by Stoltz, 2019 The bistetrahydroisoquinoline (bis-THIQ) alkaloids, a class of polycyclic natural products with significant physiological activities, have drawn

• oxygen atoms from the substrate and the metal catalyst, which fixed the conformation of the polycyclic scaffold. As a result, the top face is sterically less favored, thereby hydrogen approaches from the opposite face. The subsequent addition of another two equivalents of hydrogen also supported this

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• Morwenna Mogel David Berger Philipp Heretsch Institut für Organische Chemie, Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany 10.3762/bjoc.21.206 Abstract The Veratrum alkaloids constitute a class of natural products with particularly intricate polycyclic frameworks and

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

• desired polycyclic compounds 35 in a moderate level of enantioselectivity (Scheme 14) [64]. Conclusion In conclusion, over the past two decades, organocatalyzed visible-light-promoted radical chemistry, particularly dual photocatalysis combining N-heterocyclic carbenes (NHCs) with organic photocatalysts

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

• and future trends in the total synthesis of natural products from this family. Natural products derived from the Ryania genus comprise a class of structurally intricate polycyclic diterpenoids isolated from the Central and South American shrub Ryania speciosa (Scheme 1) [8][9][10][11][12][13][14

• and structurally established [16][17][18]. Structurally, ryanodine (1) and related diterpenoid natural products feature a 6-5-5-5-6 pentacyclic core skeleton containing 11 stereocenters, eight of which are quaternary carbons. A key structural feature is the assembly of a polycyclic cage-like framework

• ingenol [55]. Typically, the biosynthesis of polycyclic diterpenes occurs in two distinct phases: an initial cyclase-mediated cyclization phase to form the carbon framework, followed by an oxidase-catalyzed phase to install the requisite oxidation states. Inspired by this general biosynthetic pathway, the

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• observed for these annulated molecules, while their analogous non-annulated control compounds were not bioactive. Keywords: annulation; arenes; antimicrobials; fused-ring systems; UV–vis spectroscopy; Introduction Polycyclic aromatic heterocycles are a diverse class of small molecules with utility in a

• physical and biological properties of such polycyclic aromatic heterocycles would serve as an initial evaluation of their potential use in chemical, material, and therapeutic applications. Results and Discussion The two-step approach used to prepare the target pentacyclic aromatic heterocycles 13–18 via

• reactivity of this family of pentacyclic aromatic heterocycles towards N-benzylation and the antimicrobial properties of such resulting quaternary ammonium compounds are ongoing. Examples of polycyclic aromatic heterocycle structures: phenanthridine (left), 1,5-naphthyridine (center), and 1,9-phenanthroline

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• excellent conversion rates (up to 95% yield) and high enantioselectivity (up to 96% ee). Notably, isoquinoline derivatives containing polycyclic naphthalene moieties or ortho-substituted phenyl groups also demonstrated good reactivity and compatibility. DFT calculations indicated that the C–Se bond

• ]. When a para-fluorine substituent is present on the naphthalene ring of the substrate, the reaction proceeds with a yield of up to 90% and an enantioselectivity reaching 92% ee. The methodology demonstrates a broad substrate scope, accommodating various polycyclic naphthalene isoquinolines as well as

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

• with a yield of 51% (Scheme 28). As a result of the photolysis of 5,6-epoxy ketones 146 and 152, valuable derivatives of cyclopentane, 147a,b, 151, and 153 were obtained. Photochemistry is an important tool in the synthesis of natural and synthetic biologically active substances based on polycyclic

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

• stereochemical inversion of the Norrish–Yang reaction. This achieved efficient construction of benzofuranone-based 4,5-spirocycles with contiguous all-carbon quaternary centers, offering a conformational regulation protocol for stereocontrol in complex polycyclic systems. 1.3 Avarane-type meroterpenoids In 2024

• ingenuity lies in utilizing the inherent conformational constraints of the substrate instead of external chiral catalysts, which not only simplifies the reaction system but also solves the challenge of precisely controlling contiguous chiral centers in polycyclic systems. Conclusion This review

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• polycyclic products in a highly diastereo- and enantioselective manner [45]. The polyene substrates were designed to facilitate a radical cyclization process, with alternating electron-poor and electron-rich olefins so as to enable polarity matching of the olefins and radical intermediates. With this design

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

• solvent-controlled selective syntheses of two polycyclic compounds (Scheme 6) [13]. Using PdCl2 as the catalyst and DMF as the solvent, substrate 22 underwent a 6-endo-dig cyclization and subsequent enone insertion, forming a palladium–carbon bond intermediate. Protonolysis yielded isocoumarin-fused

• polycyclic aromatic heterocycles (Scheme 15) [23]. Catalysts bearing the strong σ-donating IPr ligand exhibited a marked preference for the 5-exo-dig cyclization pathway, affording five-membered ring product 70 (Scheme 15, path a). When a bulky Me4XPhos ligand was employed, the reaction favored 6-endo-dig

• constraints promoted intramolecular Friedel–Crafts cyclization via intermediate 84 to form spiro-polycycle 86 (Scheme 18, path b). The ligand-dependent gold(I)-catalyzed cyclization provided modular access to therapeutically significant fused polycyclic heterocyclic scaffolds via regioselective ring expansion

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• /bjoc.21.167 Abstract A one-pot Ugi–azide reaction followed by intramolecular Cu-free azide–alkyne cycloaddition generates a polycyclic scaffold 7 bearing polycyclic triazole, tetrazole, and benzodiazepine rings. This method could be extended for obtaining a more complicated scaffold 8 containing a

• piperazinone ring. Keywords: benzodiazepine; click reaction; multicomponent reaction; one-pot; piperazinone; polycyclic; triazole; tetrazole; Ugi–azide reaction; Introduction Triazole, tetrazole, and benzodiazepine are privileged heterocyclic rings commonly found in drug molecules and functional materials [1

• in 36–90% yields (Scheme 4). As shown in Scheme 2, we also propose the synthesis of triazole-, tetrazole-, and piperazinone-fused 1,4-benzodiazepines 8. For the synthesis of this unique polycyclic scaffold, 2-isocyanoacetate 9 played a critical role in the formation of the piperazinone ring. Thus

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

• fuels driven by solar energy such as non-symmetrical polycyclic hydrocarbons has been proposed by using a photosensitized Conia reaction of ketones and norbornene (Scheme 67) [212]. The hydrocarbons derived from CPN and cyclohexanone endow high density of 0.935 and 0.941 g mL−1, respectively, much

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

• (−)-aspidospermidine (−)-Hunterine A (14) and (−)-aspidospermidine (15) are monoterpene indole alkaloids, which were isolated from Hunteria zeylanica and Apocynaceae plants, respectively [56][57]. Structurally, these two natural products both contain the fused polycyclic skeleton core bearing four consecutive

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

• polycyclic structures, DNA was not the primary target for their antiproliferative effects, as confirmed by FID assay and fluorescence titration studies. This study represents the first comprehensive evaluation of indolo[1,2-c]quinazolines as potential scaffold for the development of antitumor agents

• (positions 5, 6, and 12) with anticancer activity, thereby establishing indolo[1,2-c]quinazolines as a novel and underexplored platform for drug discovery. Results and Discussion Planar polycyclic compounds including classical frameworks such as acridine, anthraquinone, naphthalenediimide, etc. demonstrate

• exceptional potential as ligands targeting secondary structures of nucleic acids, particularly G-quadruplexes (G4) [21][22]. The indolo[1,2-c]quinazolin-6(5H)-one scaffold 1 exemplifies this design principle, with its rigid polycyclic framework mimicking topologies of established DNA/RNA-interactive molecules

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

• TsOH was used, sarglamides D and E could be obtained with a 1:1 ratio, as conducted by Yue [43] and Tong [45] research groups. In our hand, we used an excess amount of TsOH (3.0 equiv), and found that sarglamide E was generated exclusively. Ultimately, a powerful total syntheses of complex polycyclic

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• the formation of two new rings and a complex polycyclic product from relatively simple starting materials. To test the scope of the chemistry, we screened several other dipolarophiles for this transformation. As expected, the related N-phenylmaleimide resulted in the formation of the analogous N

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

• reaction mechanisms and applications of the chiral products for selected examples. Review Helical chirality Helicenes are a group of rigid polycyclic aromatic compounds composed of ortho-fused aromatic (hetero)cyclic rings, with their helically twisted conformation enforced by steric hindrance between

• and polycyclic ketone 2, they achieved the efficient asymmetric synthesis of various helically chiral azahelicenes 3 (Scheme 1). To address the inherent length-scale challenges of molecular helicene frameworks, the authors designed and synthesized novel CPAs bearing extended π-substituents at the

• aromatization process, in 2023 our group reported the asymmetric synthesis of various azahelicenes 8 from polycyclic arylamines 5, dienamides 6 and aldehydes 7 (Scheme 2) [13]. This methodology demonstrates a broad substrate scope, enabling the efficient asymmetric synthesis of diverse aza[5]helicenes 8a–d and

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• concluded that the aromatic character of the fluorophore is better described as the combination of two aromatic subunits integrated in the polycyclic system. Different DFT functional are used to analyze the photochemical behavior of this family of sensors. It is concluded that PBE0 and M06 functionals

• decoupling between the para-phenylene and benzo[a]imidazo[5,1,2-cd]indolizine components that results in a blue shift upon Ba2+ coordination. Keywords: aromaticity; DFT-TDDFT calculations; double-beta decay; fluorescent sensors; polycyclic arenes; Introduction Double beta-decay [1] is a radioactive decay

• the molecular plane [25][26] since diatropic ring currents are observed over the centers of the four ring points of electron density. However, the issues associated with magnetic criteria to describe the aromaticity of polycyclic systems must be taken into account. Thus, a recent study [27] emphasizes

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• , Japan 10.3762/bjoc.21.119 Abstract The intramolecular oxidative fusion reaction of macrocyclic heteroaromatic arrays has provided strained polycyclic heteroaromatic macrocycles as promising functional molecules. In this study, we prepared an ortho-phenylene-pyrrole-thiophene hybrid icosamer, as the

•  1) [6][7][8][9][10][11][12]. Nevertheless, partially fused macrocyclic intermediates are also important as they exhibit structural strain associated with both the polycyclic segments and the inherent strain stemming from the macrocyclic structure. For instance, cyclic chrysenylenes [13][14][15][16

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

• Meng Qiu Jing Du Nai-Te Yao Xin-Yue Wang Han-Yuan Gong College of Chemistry, Beijing Normal University, Xinjiekouwaidajie 19, Beijing, 100875, China 10.3762/bjoc.21.106 Abstract Helicenes, a class of non-planar polycyclic aromatic hydrocarbons composed of ortho-fused aromatic rings forming

• ; optoelectronic applications; Introduction Helicenes, a class of non-planar polycyclic aromatic hydrocarbons characterized by ortho-fused aromatic rings forming a helical framework, have attracted significant attention due to their inherent chirality, unique optoelectronic properties, and wide-ranging

• synthesizing azahelicenes and diaza[8]circulenes 65a–d [24] (Table 22). These molecules exhibited distinct Cotton effects and CPL, with |glum| reaching up to 1.6 × 10−3. This approach offers a generalizable route to structurally diverse chiral polycyclic aromatic hydrocarbons (PAHs) with strong chiroptical