Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• ][13][14][15][16][17][18][19]. The ring-opening reactions of bicyclic epoxides are of significant importance and scientific interest due to their high ring strain, their strategic role in the construction of complex molecular architectures, and their utility in the synthesis of natural products

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• chemistry, as it exemplifies the successful translation of marine natural products into effective therapeutic agents. The clinical importance of 1 primarily stems from its efficacy in treating aggressive and refractory cancers, notably metastatic breast cancer and liposarcoma [31][32][33][34][35

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

• distal axial chiralities are widely applied in chiral ligands, natural products, and anticancer agents, with their unique spatial configurations endowing them with distinctive functions and values. Although significant progress has been made in the asymmetric synthesis of distal biaxial chirality

• catalysis [26]. These molecules are widely found in natural products [27] and drugs, such as michellamines A and B [28], korupensamines A and B [29], diazonamide A [30], mastigophorene A [31], and the recently developed drug candidate BMS-986142 [32] (Figure 1). When a molecule contains two or more chiral

• often difficult to control [37], particularly for remote biaxial systems (1,3-biaxial and beyond), where diastereoselectivity and enantioselectivity are challenging to regulate. Various multiaxial chiral natural products with high biological activity exist in nature [28], and in artificial synthesis

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• . Keywords: amide; amide activation; esterification; non-activated amide; transamidation; Introduction Serving as a cornerstone in organic chemistry, the amide bond is a fundamental and extensively utilized functional group, playing a central role in natural products, biomolecules, and functional materials

• conditions, several types of fluorinated alcohols were successfully employed as nucleophiles, generating the corresponding esters in good to high yields. Notably, the method displayed excellent chemoselectivity for primary amides. Therefore, multifunctional substrates derived from natural products or

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

• tailoring, will be examined and discussed. Where possible, biogenetic relationships of closely related families of natural products will be contextualised by showing the mechanistic rationale for their interconversion. In the second part of this article, the application of bioinspired ring contraction and

• ring-expansion strategies in relevant natural product syntheses will be presented, demonstrating how synthetic chemistry can help to elucidate plausible biogenetic routes for structurally complex natural products. Keywords: biosynthesis; rearrangement; ring contraction; ring expansion; skeletal

• editing; terpenoids; total synthesis; Introduction The vast richness of structural diversity in terpenoid natural products has fascinated organic chemists for more than a century now [1][2][3][4][5]. With more sophisticated techniques for isolation and characterisation emerging over the decades

Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• been used in the synthesis of numerous pharmaceuticals and natural products [7]. The application of asymmetric synthesis enables access to enantiomerically pure targets. Earlier, metal catalysis was used for Mannich reactions [8][9], but in recent years, methods of asymmetric organocatalysis have been

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

• saturation the aromatic ring facilitates synthetic chemists to efficiently synthesize natural products with complex three-dimensional structures. Recent advances in catalyst and ligand design have enabled unprecedented progress in the catalytic hydrogenation of (hetero)aromatic systems. Quinoline

• synthesis of complex natural products and pharmaceutical agents. This review highlights recent advances in catalytic (hetero)arene hydrogenation, with a focus on its application in natural product synthesis. Keywords: aromatic rings; dearomatization; hydrogenation; natural products; total synthesis

• ; Introduction For decades, a principal objective in natural product synthesis has been the development and utilization of efficient methods to access molecular frameworks with defined stereochemical complexity [1]. Natural products, such as taxol [2], strychnine [3][4][5], and tetrodotoxin [6][7][8], which

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• with pinacol in the presence of Et3N. This transformation was likewise applicable to a broad range of alkyl chlorides, affording the corresponding alkylboronates 40a–j in good yields. The bibenzyl skeleton is commonly found in numerous natural products and bioactive compounds [23][24][25], and the

• benzylic position, giving the hydrogenated products with high site selectivity. Zr-catalyzed radical reaction in the total synthesis of complex natural products This section presents examples of zirconium-mediated reactions applied to the synthesis of complex molecules. For application in total synthesis

• total synthesis of the halichondrin family of natural products (Scheme 11) [37][38]. Ketone 57, an intermediate in the synthesis of halichondrins, bears a β-alkoxy substituent, which raises concerns about potential epimerization via a retro-oxa-Michael/oxa-Michael pathway (Scheme 11A). To address this

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• caliche deposits in Chile [2]. This concentration of supply raises potential concerns regarding long-term availability and geopolitical vulnerability. Recent interest in alkenyl chlorides has been driven by their occurrence in bioactive natural products (Figure 1) [3][4][5], pharmaceuticals (Figure 2) [6

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• phytopathogenic fungi. Keywords: ammonium dinitramide; antifungal agents; azoxy compounds; electrosynthesis; NO donors; Introduction Organic compounds containing N–N and N–O bonds are ubiquitous in diverse fields, including pharmaceuticals, agrochemicals, natural products [1][2][3][4], as well as in

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• Bock in 1987 [16]. It is of interest that although the biosynthesis of 3-indolylbenzoquinone-2,5-dione ent-5 is initiated with ʟ-tryptophan and anthranilic acid [17], the resulting natural products 1–4 possess a (3R) configuration. This is because of an epimerization mediated by the non-ribosomal

• relatively simple structures, we considered two basic approaches to 4-, 5-, 6-, and 7-prenylated tryptophans as synthetic precursors which could be converted to the intended natural products by cyclization to benzodiazepine-2,5-diones or diketopiperazines. First, is the evident use of tryptophan as a

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

• . For an overall comparison of the strategies in the synthesis of jervanine-type natural products, we aimed to achieve a visual comparison via color-coded schemes proposed by the Christmann group (Scheme 15) [10]. In direct comparison, the Giannis synthesis of cyclopamine [21] as the oldest synthesis

Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• ; C–H hydroxylation; chemoenzymatic synthesis; Mukaiyama hydration; protecting-group-free synthesis; Introduction Cardiac glycosides (CGs) are widely distributed natural products, generated by plants and amphibians [1]. Structurally, they are composed of an aglycone-steroidal moiety, an unsaturated

• natural products. Representative CGs with promising biological activities. Retrosynthetic analysis of rhodexin A and sarmentogenin. Chemoenzymatic synthesis of sarmentogenin (2). Synthesis of rhodexin A. Optimization of the fermentation conditions of the biocatalytic C14–H α-hydroxylation. Supporting

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• (Caryophyllaceae), are head-to-tail cyclic oligopeptides comprising 5–9 amino acid residues [5][6][7][8][9][10][11][12][13]. These natural products exhibit a significant diversity of pharmacological activities [14][15][16], including estrogen-like activity (1, 2, 7, 8), antitumor effects (5), and antimicrobial

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

• organic chemistry, and particularly in the late-stage functionalization of bioactive compounds, drugs, and natural products. This review highlights recent advances in NHC–organophotoredox dual catalysis, focusing on methodology development, mechanistic insights, and reaction scope for synthesizing

• ; NHC; organic photocatalyst; radicals; visible-light; Introduction Over the last ten years, NHC-catalyzed visible-light-promoted radical chemistry has been extensively developed for the cost-effective and practical synthesis of bioactive intermediates, pharmaceuticals, drugs, and natural products [1

• functional groups are found in various drugs, natural products, and optoelectronic materials. In the last three decades, N-heterocyclic carbenes (NHCs) have been renowned as versatile organocatalysts, including thiazolium, imidazolium, and triazolium moieties. NHCs are extensively used in many catalytic

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• total synthesis. Keywords: bioinspired synthesis; biosynthetic pathway; Illicium sesquiterpene; illisimonin A; total synthesis; Introduction The genus Illicium, the sole member of the family Illiciaceae, is a rich source of sesquiterpenoid natural products. To date, a wide variety of sesquiterpenes

• , pseudomajucin-subtype, cycloparvifloralone-subtype, majucin-subtype, and miwanensin-subtype (Figure 1). The seminal work by the Fukuyama group demonstrated that some of these natural products exhibit potent neurite outgrowth-promoting activity in primary cultured rat cortical neurons, which has attracted

• proposed that a deeper understanding of the biosynthetic pathway of Illicium sesquiterpenes could facilitate a divergent total synthesis of this family of natural products, even among members with distinct carbon skeletons. Since previously proposed biosynthetic pathways lacked key mechanistic details

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

• enhance synthetic efficiency, reduce costs, and provide robust solutions to challenges encountered in the synthesis of complex molecular architectures. Ryania diterpenes are natural products characterized by intricate structures and high oxidation states. Biological studies have revealed that the family

• focuses on reviewing the efficient application of ring-construction methods and synthetic strategies in the total synthesis of highly oxidized Ryania diterpenoid natural products, emphasizing the pivotal role of novel synthetic methods and strategic innovations. Keywords: natural products; Ryania

• diterpenoids; synthetic strategy; total synthesis; Introduction Organic synthesis, as a cornerstone of chemical research, is dedicated to constructing complex natural products or target molecules from simple and readily available starting materials via a series of precise and efficient chemical reactions

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

• the tropical rain forests of the Kalimantan region (Indonesia) [1][2]. These cyclic ether natural products belong to the typical aryltetralin lignans, which have already attracted broad attention from the synthetic community [3][4][5]. Zhu and co-workers disclosed a concise synthesis of (±)-aglacins B

• the formation of inter- or intramolecular carbon–carbon bonds under mild conditions [9][10][11][12], and strategically applied this method for the divergent syntheses of some natural products [13][14][15][16][17]. Herein, we report our recent advance to a total synthesis of (+)-aglacin B (2), which

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• ; palladium; Introduction Carbazole represents an important heterocyclic scaffold that is broadly present in many natural products, biologically active motifs, as well as optoelectronic and functional materials [1][2][3][4][5][6][7][8]. By virtue of its substantial application in various fields, significant

• developed a regioselective protocol for the direct C1–H nitration of carbazoles, an important class of heterocycles with wide-ranging applications in materials science and natural products chemistry. The transformation proceeds using commercially available Pd2(dba)3 as the catalyst and silver nitrate as the

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

• University, Liaoning Shenyang 110016, China 10.3762/bjoc.21.189 Abstract Natural products with topologically complex architectures are important sources in drug discovery. The pursuit of conciseness and efficiency in the total synthesis of natural products promotes continuous innovation and the development

• current interest in the synthesis of complex natural products via photochemical reactions, we decided to achieve such an unusual bond cleavage (Figure 1a, path A) of cyclobutenone by generating a radical cation species via a PET reaction. The synthetic plan is shown in Figure 1c and includes a PET

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

• Atropisomers are not only prevalent in biologically active natural products and pharmaceuticals, but they have also garnered increasing attention for their effectiveness as ligands and catalysts in the field of catalytic asymmetric synthesis. Asymmetric catalysis serves as a key strategy for the

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

• acid (DMOA), are a large series of hybrid natural products with a huge structural diversity and impressive biological activity [50]. Attempts by the authors to use acidic (TiCl4, TMSI, SnCl4), basic (NaOMe, t-BuONa, Et3N, DBU, DMAP) and thermal conditions (PhMe, 110 °C) failed to give the desired

• seconorrisolide C (130) from Wieland–Miescher ketone derivative 131. The spongian diterpenes are a large family of marine natural products that have pronounced effects on the Golgi apparatus [67]. The introduction of the diazo group into ketone 131 was achieved under standard conditions through an α-formyl

• multiple stereocenters, including contiguous quaternary carbons. As a result, the carboborative ring contraction reaction is conveniently used for structural modification of natural products containing a cyclohexene ring and in the synthesis of new compounds to increase their activity, metabolic stability

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• -unsaturated ketone; dearomatization; indole; spirocyclization; spiro[indoline-3,2'-pyrrolidine]; Introduction Spiro[indoline-3,2'-pyrrolidine] derivatives represent an important class of organic compounds found in both natural products (e.g., coerulescine [1], horsfiline [2], and elacomine [3]) and synthetic

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• Liang Shi Jiayi Song Yiqing Li Jia-Chen Li Shuqi Li Li Ren Zhi-Yun Liu Hong-Dong Hao Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, China 10.3762/bjoc.21.182 Abstract A synthetic study toward

• ; Introduction β-Lactones have attracted continuous interest and have been widely utilized as key intermediates in the synthesis of natural products and polymers due to their innate ring strain [1][2][3][4][5][6]. Moreover, several natural products and their derivatives containing β-lactone as key structural

• outcomes. As intermediate 13 may serve as a valuable precursor to vibralactone (6) and other congeners such as vibralactone E (7), an alternative synthetic route toward 13 is currently being carried out in our laboratory and will be reported in due course. Selected representative natural products and

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

• synthesis of natural products but also establish a solid foundation for subsequent pharmaceutical investigations. Keywords: dicarbonyls; natural product; Norrish–Yang cyclization; photoredox; total synthesis; Introduction In the 1930s, Norrish documented the photodecomposition of aldehydes and ketones [1

• , α-keto amides, 1,4-quinones, and 1,2-quinones in this context, have emerged as versatile substrates in Norrish–Yang cyclizations, finding widespread application in natural products synthesis. Compared to monoketones, dicarbonyls (e.g., 1,2-diketones) offer distinct advantages: (1) they generally

• -hydroxy-β-lactams or 2-hydroxycyclobutanones can function either as inherent structural motifs in target natural products or as strained reactive intermediates, facilitating C–H functionalization via four-membered ring opening [6][7][8][9][10][11]. Quinones display distinct photochemical reactivities