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

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

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China 10.3762/bjoc.21.166 Abstract Organic five-membered rings have shown significant applications in the fields of organic synthesis, natural products, organic materials and pharmaceuticals for their unique

• organic synthesis [1][2][3][4][5][6][7][8][9][10][11][12][13][14] but also are critical moieties in natural products [15][16][17][18], organic materials [19] and pharmaceuticals [20][21][22][23][24] due to their unique chemical, electrical, optical, pharmacological and biological properties. Gracilioether

• alkynes bearing heteroatoms such as ynamides and thioalkynes would be enhanced in future research; (2) since axial chirality is critical in natural products and pharmaceuticals, it would be significant to apply the electrochemical annulation of alkynes in formation of organic rings with axial chirality

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

• complex natural products. On the other hand, terpenoids and alkaloids, with their intricate and diverse skeletal frameworks as well as the broad range of biological activities, have long been a major focus for synthetic chemists. Over the past fifteen years, significant progress has been made in the total

• synthesis of complex terpenoid and alkaloid natural products by strategically applying desymmetric enantioselective reduction. Advance before 2016 in this area has been overviewed in an elegant review article. Since then, a series of more challenging terpenoid and alkaloid natural products have been

• synthesized utilizing a desymmetric enantioselective reduction strategy of cyclic 1,3-dicarbonyl compounds as a key transformation. This review will summarize the application of this strategy in the total synthesis of terpenoid and alkaloid natural products from the year 2016 to 2025. We first focus on the

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• confirmation of natural products is no longer a motivation for the total synthesis [1]. Nevertheless, we also witness that each year, cases continue to be reported on the total synthesis enabled revision of misassigned structures of natural products [1][2][3][4][5][6][7][8][9]. Efficiency is one of the major

• concerns in the field of total synthesis of natural products [10][11][12][13][14][15][16][17][18][19][20], which is not only essential for organic chemistry in its own right, but also crucial for drug discovery and structural revision of natural products. Although more and more diastereomeric and

• enantiomeric natural products have been discovered [21][22][23][24][25][26][27][28][29][30][31][32], and divergent synthetic methodology has attracted attention in recent years [33][34][35][36][37][38], diastereodivergent and enantiodivergent total synthesis remain rare [39][40][41][42][43][44][45][46][47][48

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. Recently, we have achieved an array of bioinspired total syntheses, which showed the great power of this approach in natural product synthesis. Documented herein is a review of these achievements which include the detailed process of how we develop these strategies. Specifically

• , bioinspired total synthesis of three types of natural products, namely diterpenoids (chabranol, and monocerin), alkaloids (indole, hydroquinoline, and monoterpenoid−indolidinoid hybrid), and gymnothelignans are discussed. Based on these achievements on bioinspired total synthesis, we provide some information

• on how to use this important strategy in natural product synthesis. Keywords: bioinspired total synthesis; chabranol; gymnothelignans; monocerin; sarglamides; taberginggine; Introduction Natural products are chemical substances generated within living organisms in nature. They are products of

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

• synthesis of tricyclic-PGDM methyl ester in 9 steps and 8% overall yield. Keywords: asymmetric total synthesis; oxidative radical cyclization; tricyclic prostaglandin D2 metabolite methyl ester; Introduction Prostaglandins (PGs), a family of hormone-like lipid compounds, are ubiquitous natural products

• used as a powerful method for synthesizing complex natural products [20][21]. We envisaged that the A-ring in 4 could be constructed from the alkene-substituted β-keto ester precursor A via a bioinspired oxidative radical cyclization (Scheme 1D). Herein, we report the full details of our efforts to

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• functionalization of one hydroxy group, offers beneficial procedures for accessing diverse structural motifs. In this review, we highlight a curated compilation of publications, focusing on the applications of enantioselective desymmetrization of prochiral 1,3-diols in the synthesis of natural products and

• biologically active molecules. Based on the reaction types, three strategies are discussed: enzymatic acylation, transition-metal-catalyzed acylation, and local desymmetrization. Keywords: asymmetric synthesis; desymmetrization; 1,3-diols; natural product; total synthesis; Introduction Natural products

• isolated from organisms are often asymmetric in their spatial structures, and these unique spatial structures are precisely what lead to their diverse biological activities [1][2][3][4]. For the synthesis of these natural products or bioactive molecules, chemists usually need to consider how to carry out

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• applications in the preparation of chiral ligands. Keywords: chiral piperazines; electrosynthesis; flow chemistry; green chemistry; imino-pinacol coupling; Introduction Vicinal diamines represent a highly valuable class of compounds that, over the past decades, have found widespread application in natural

• products, agrochemicals, and pharmacologically active compounds. Enantiomerically pure 1,2-diamines and their derivatives are also increasingly used in stereoselective synthesis, particularly as chiral auxiliaries or as ligands for metal complexes in asymmetric catalysis [1]. Metal-based reductants

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

• an important class of compounds with significant biological activities. Spirocyclic derivatives are present in a variety of natural products. We describe here the formation of spirooxindoles using an intermolecular nitrone cycloaddition reaction. The nitrone dipole was prepared in situ by cyclisation

• -dipole, access to 1,3-amino-alcohol functionality is possible. This arrangement is present in many Alstonia alkaloids, and we envisaged using this cycloaddition chemistry to set up the bridged amine ring system found in these natural products. Bridged and spirocyclic ring systems are known to be

• approach. This generates the desired spirooxindole connected to a bicyclic amine, with functionality related to the natural products. It is likely that unactivated dipolarophiles could be successful in related intramolecular cycloadditions [18]. Hence this approach could allow access the spirooxindole and

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

• potential applications in catalytic asymmetric reactions have also been showcased. Planar chirality Planarly chiral cyclophanes, a unique class of macrocyclic compounds featuring planar chirality, can be found in various natural products and are widely utilized in asymmetric catalysis, host–guest chemistry

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• of carbonyl compounds, such as aldehydes or ketones, with active methylene compounds [37]. The resulting α,β-unsaturated carbonyl products can then be further elaborated to form natural products, therapeutic agents, polymers, pesticides, and insecticides [38], which have important applications in the

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• the [3.2.1] motif as the SERMs in Scheme 1 do. Lei used a [3 + 2 + 1] reaction [23][24][25][26][27][28], which was developed in our group and has been applied in synthesis, coupled with stoichiometric Pd-mediated Heck reaction, concisely reaching the framework of their target natural products. We

• position, which could be the key to Lei’s synthesis. Realizing the synthesis of VI would provide a practical strategy not only to our target here but also to other natural products with [3.2.1] framework such as songorine, beyerene, garryine and steviol shown in Scheme 3B. Results and Discussion Scheme 4

• reaction in synthesis. Reported biologically active tetrahydrofluorenone-SERMs molecules. Reported synthesis routes to SERMs molecule VI. Lei’s synthesis of natural products of ent-kaurane diterpenoids (A), and natural products songorine, beyerene, garryine and steviol (B). Retrosynthetic analysis for the

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

• used in the synthesis of a good number of target molecules, including complex natural products [32][33][34][35]. Typically, the LA binds the dienophile through a donor–acceptor interaction (usually involving a carbonyl group) which results in a significant stabilization of the dienophile’s LUMO. As a

• natural products such as (+)-steenkrotin A [64] or (±)-andrastin C [65], among others. In order to understand the factors leading to the observed reactivity enhancement, we first compared the parent carbonyl–ene reaction between 1-butene and acetaldehyde with the analogous processes catalyzed by different

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

• biosynthesis; P450 oxidation; synthesis; Introduction Fusicoccanes are a family of 5-8-5 tricyclic diterpenoid natural products that are produced by bacteria, fungi, algae, and plants (Figure 1a) [1][2][3][4][5][6][7]. Fusicoccanes possess a broad range of biological activities, including anticancer, anti

• enzymatic terpene cyclization and chemical synthesis [30][31][32][33]. Briefly, the carbon scaffolds are forged by terpene cyclases, followed by concise chemical transformations to yield the desired natural products. Here, we describe heterologous biosynthesis of cotylenol by engineering the biosynthetic

• brassicicene biosynthesis-related gene cluster (BGC) in Alternaria brassicicola and Pseudocercospora fijiensis [34][35]. The 5-8-5 tricyclic scaffold is transformed into various fusicoccane natural products catalyzed by P450s, dioxygenases, dehydrogenases, and reductases. Therefore, we propose to harness the

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

• human system. In this study, we isolated two previously undescribed N-salicyl-amino acids as natural products (1 and 2) and other two new derivatives (3 and 4) from the organic extract of a culture broth in a modified starch–glucose–glycerol (SGG) medium of Pseudomonas sp. UIAU-6B. The structure of the

• new natural products, pseudomonins D–G (1–4) isolated alongside other three known compounds, pseudomonine (5), pseudomonin B (6) and salicylic acid (7), were elucidated based on high-resolution mass spectrometry, 1D and 2D NMR analyses. The absolute configurations of the threonine residue in compounds

• Pseudomonas are huge producers of bioactive natural products with a vast array of structural and functional molecular diversity. This reflects in the bacteria’s genome which ranges in size from 4.6 to 7.1 megabases with 4237 to 6396 predicted genes [1]. Natural products play a major role in the live of these

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• of ring-opening and ring-expansion reactions, and finally total syntheses of selected oxetane-containing natural products. The literature review primarily covers reports made after the year 2015, but a few older contributions that were considered relevant are also discussed. Keywords: medicinal

• chemistry; natural products; oxetane; reactivity; synthesis; Introduction Oxetanes are 4-membered heterocyclic compounds containing one oxygen atom whose discovery dates back to the 1870s when the first synthesis of the parent, unsubstituted oxetane was reported by Reboul [1]. Over the next 100 years, it

• vitro [19]. As for natural occurrence of oxetanes, they are relatively uncommon, and an extensive review has recently been published by Dembitsky which explored the structural features and biological activities of oxetane-containing natural products [20]. Some of the most famous examples are taxol [21

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• C(sp3)–H in polyolefins addressed by amidyl radical under visible light. Site-selective C(sp3)–H bromination implemented by amidyl radical under visible light. Site-selective chlorination of C(sp3)–H in natural products implemented by amidyl radical under visible light. Alkylation of C(sp3)–H