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

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• ; Introduction Natural products, owing to their structural complexity, diversity, and therapeutic potential, have continued to serve as inspirations for the development of novel synthetic methodologies and strategies. In turn, these methodological and strategic advancements have significantly improved the

• efficiency and step-economy of natural product total synthesis. This symbiotic relationship has also helped to accelerate natural product biological evaluation and the subsequent biomedical development [1]. Lycopodium alkaloids are one of the largest families of natural products [2], from which famous

• activity relationships, and generation of synthetic analogs, all of which pave the way for further study and development of this unique natural product and/or its analogs. Complanadine natural products and their plausible biosynthesis. The Siegel total synthesis of complanadine A enabled by [2 + 2 + 2

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

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

• Baeyer–Villiger oxidation affording the fluorinated, chlorinated, and brominated dideoxyribonolactones. Keywords: butyrolactone; cyrene; fluorine; halogenation; levoglucosenone; Introduction The γ-butyrolactone ring is a privileged scaffold found in natural products and can be used as a valuable

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

• significant reaction, 1,n-enyne cyclization is capable of constructing a variety of complex small-molecule frameworks, including fused and bridged rings, thereby serving as a potent tool in the syntheses of natural products and pharmaceuticals. Our group has pioneered the concept of "pathway economy" by

• could be further derivatized (e.g., via borylation, epoxidation), establishing a versatile platform for accessing fused-ring natural products. Substituent-controlled cyclization of 1,n-enynes In transition metal-catalyzed cyclization reactions, the electronic properties and steric hindrance of

• ]quinolizine framework 46 (Scheme 10, path b). This controllable approach provided an efficient synthetic pathway for the related natural products. In 2020, a gold-catalyzed divergent synthesis of bicyclo[3.2.1]oct-2-ene and bicyclo[3.3.1]nonadiene derivatives from 1,6-cyclohexenynes was reported by Davenel et

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

• Chemveda Life Sciences for providing laboratory facility for carrying these research experiments. This research has been performed also as part of the Indo-French “Joint Laboratory for Natural Products and Synthesis towards Affordable Health”. We thank CSIR, CNRS and University of Rennes 1 for their

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• A terminal 3-methylpent-4-en-2-ol (MPO) moiety is a common structural feature in various polyketide natural products. Stereochemical assignments of this moiety have mainly relied on computational analyses of NMR, ECD, and specific rotation data. However, none of these approaches can be applied to

• the stereochemical assignment of (+)-capsulactone (1). Keywords: chemical degradation; chiral LC–MS analysis; methyl 3-hydroxy-2-methylbutanoate; 3-methylpent-4-en-2-ol moiety; p-nitrobenzoyl ester; Introduction Configurational elucidation of natural products is essential for progress in diverse

• structural elucidation of complex natural products at microgram quantities, facilitating the discovery of novel bioactive compounds [1][2]. However, a definitive approach for stereochemical determination that can be applied across all compound classes has yet to be established. Relative configurations are