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

• (44) would trigger a quinone-based Norrish–Yang cyclization, enabling divergent synthesis of these meroterpenoids (or their core structures). In Yang's divergent total synthesis, Wieland–Miescher ketone (18) served as the starting material. Selective acetalization of the non-conjugated ketone in 18

• generated diverse biradical intermediates via regioselective hydrogen transfer (δ-H or ε-H), further constructing various C–C bonds. This enabled efficient synthesis of the core skeletons of five natural products. The divergent strategy significantly reduces redundant synthetic steps, embodies synthetic

• gracilisoids A–I (49–57) [36]. Gracilisoids A–E (49–53) were isolated from the ethnomedicinal plant Eurysolen gracilis of the Lamiaceae, while UPLC-MS/MS analysis of the crude leaf extract indicated trace amounts of gracilisoids F–I (54–57) in the plant material. Li’s group pursued the divergent total

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

• , P. R. China Institute of Drug Research in Medicine Capital of China, Benxi 117000, P. R. China 10.3762/bjoc.21.173 Abstract This review presents a paradigm-shifting "pathway economy" strategy for 1,n-enyne cyclization, enabling divergent construction of complex molecular architectures from a single

• regioselective syntheses of indene, indenone, and naphthalene derivatives from simple aromatic 1,5-enyne substrates. In 2020, a solvent-controlled strategy for Au(I)-catalyzed divergent syntheses of phenanthrene and dihydrophenanthrene derivatives was developed by the Rodríguez group (Scheme 3) [10]. In

• radical initiated intramolecular cascade cyclization of 1,n-enynes to provide structurally diverse heterocycles (Scheme 4) [11]. Solvent selection dictated divergent reaction pathways under I2/TBHP oxidation. When an acetonitrile/water mixed solvent was used, iodine radical addition to the alkyne

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

• that this report provided a switchable and green synthetic methodology for skeletally diverse indoles. Divergent electrochemical cyclization of 2-ethynylanilines was developed to synthesize indoles and iodoindoles (Scheme 4) [188]. Treatment of 2-ethynylanilines 10 with KI in DMSO/H2O in an undivided

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

• (−)-4-bromohamigeran B (12) were synthesized by a divergent manner with a longest linear sequence of 14 steps from the known symmetrical diketone 28 (see Scheme 1) [14]. More importantly, this route allowed for the synthesis of target compounds at 100 mg scale in a single batch. As shown in Scheme 4 [51

• stereocenters, two of which are all-carbon quaternary stereocenters. Such a skeletally extraordinary structure poses significant challenges for total synthesis. In 2024, Stoltz and co-workers finished the divergent enantioselective total synthesis of (−)-hunterine A and (−)-aspidospermidine by utilizing a Ru

• enantioselective reduction of 1,3-cyclohexanedione derivative 89 as the key transformation [72]. Both (−)-conidiogenones B–F (17–21) and (−)-12β-hydroxyconidiogenone C (22) were synthesized in a divergent manner. Their synthetic route began with the known terminal alkyne cyclohexanedione 89 [73]. As illustrated in

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

• 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

• divergent coupling approaches, and the stereocontrol with Evans oxazolidinone was always reliable to obtain an sole diastereomer (Scheme 6d). Bioinspired concise and scalable total synthesis sarglamides In 2023, Yue and co-workers investigated the ingredients of the Chinese folk medicine Sarcandra glabra

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

• allylation to install the side chain at C8, and a diastereoselective spirolactonization to generate the spiroketal moiety in 26. This total synthesis is promising for divergent total syntheses of other PGs and structurally related pharmaceutical derivatives. Representative prostaglandins and general

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

• 175 in a divergent synthesis of 3,3-disubstituted oxetane amino esters 176 based on a facile, strain-release-driven Giese addition of nitrogen- or oxygen-stabilised radicals (Scheme 44) [96]. The radicals were generated through a photochemical oxidative decarboxylation of amino- or alkoxycarboxylic

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• intermediate 12. Subsequent intramolecular cyclization and oxidative aromatization lead to the final isoxazoline-featured oxindole 9. In 2017, Li’s group reported an oxidative divergent bicyclization of 1,n-enynes through α-C(sp3)–H functionalization of alkyl nitriles using a Sc(OTf)3 and Ag2O system (Scheme 7

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• system rather than a bridged tricycle. Building on this strategy, the same research group developed a divergent synthetic route that culminated in the concise and collective total synthesis of a series of fawcettimine-type Lycopodium alkaloids (Scheme 2) [21], which are well-known for their potent

• annulation and applied it in the divergent total synthesis of Cephalotaxus alkaloids (Scheme 3) [22], including cephalotaxine whose ester, homoharringtonine, has been listed as an approved FDA drug for the treatment of chronic myeloid leukemia [23]. In their elegant study, an Au-catalyzed [2 + 3] annulation

• divergent total synthesis of several Cephalotaxus alkaloids. The α-hydroxylation of cyclopentanone, followed by amide reduction and methanol elimination in one-pot, produced (−)-cephalotaxine in 9 steps. Alternatively, Riley SeO2 oxidation of 31, benzylic bromination/hydrolyzation, facial selective ketone

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• development, advanced materials innovation, and fundamental molecular science research. In recent years, controllable/divergent synthetic strategies for organic functional molecules using common starting materials have garnered significant attention due to their high efficiency. This review categorizes recent

• literatures focusing on key regulatory factors for product divergent formation, in which controlling chemical selectivity primarily relies on ligands, metal catalysts, solvents, time, temperature, acids/bases, and subtle modifications of substrates. To gain a deeper understanding of the mechanisms underlying

• reaction activity and selectivity differentiation, the review provides a systematic analysis of the mechanisms of critical steps through specific case studies. It is hoped that the controllable/divergent synthesis concept will spark the interest of practitioners and aficionados to delve deeper into the

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• give satisfactory reproducibility. Histidine/Tyr More recently, the same research group demonstrated the divergent functionalization of tyrosine or histidine, thanks to the use of a DNA photoswitch Ru complex, either used as a standalone system or involved in an artificial metalloenzyme (ArM). The use

• of biological and aqueous media. When applied to trastuzumab, the artificial metalloenzyme system ([Ru] ⊂ RFBP) thus yielded striking results – significantly reducing undesired tyrosine modifications on the heavy chain while enabling selective modification of histidine. This impressive divergent

• /illustration/monoclonal-antibody-igg2a-lizenfreie-illustration/585105259?searchscope=image%2Cfilm&adppopup=true; ALFRED PASIEKA/SCIENCE PHOTO LIBRARY, No. 585105259. This content is not subject to CC BY 4.0. Schematic procedure of the divergent method developed by Sato et al. on histidine/tyrosine photoinduced

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• ). Synthesis of preQ1 and DPQ1 derivatives with electrophilic handles For the synthesis of haloalkyl- and mesyloxyalkyl-modified preQ1 and DPQ1 ligands 3a,b and 4a–e (for target structures see Scheme 1), a divergent synthetic route was sought that provided flexibility with respect to linker length and nature

• aqueous hydrobromic acid provided 3c. Conclusion We have developed a divergent synthesis of 7-aminomethyl-7-deazapurines (preQ1 and DPQ1) with various electrophilic handles extending the aminomethyl moiety. These derivatives are capable of covalent tethering to the preQ1-I RNA aptamer. This aptamer occurs

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• , 70:30 anti/syn). This indicates a unique divergent photomechanochemical reaction pathway with respect to the simple irradiation in solid state. Remarkably, no selectivity was observed in solution state (DMSO as solvent), while a completely reversed selectivity (99%, anti/syn 91:9) was obtained when

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• new selective non-cannabinoid ligands due to the important motor impairment found in mice lacking GPR55 [51]. In this context, ML192 analogs were synthesized employing a divergent synthetic route starting with a multicomponent reaction, the Gewald reaction (Scheme 13). This reaction allows to easily

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• example, halogen-containing resorcin[n]arenes are highly sought after as they engage in divergent synthesis [8][63][64][65][66][67][68]. However, 2-haloresorcinol does not cyclize under standard protocols (Scheme 1a) pushing the need for an additional halogenation step (Scheme 1b). To overcome this

• manner, and from the few reports using 2-bromoresorcinol, it has been described to yield inseparable mixtures of oligomers [9][59]. Electron-withdrawing groups like carboxylic acids are another useful functional group instead of the halogen that provide a divergent route to other functional materials

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• halo-divergent strategy from known 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-ᴅ-mannopyranose. In solution and in the solid-state, all analogues adopt standard 4C1-like conformations despite 1,3-diaxial repulsion between the F2 and the C4 halogen. Moreover, the solid-state conformational analysis of

• predictions of such compounds remain very challenging [32]. Results and Discussion Our recent discovery that the nature of halogen atoms can have a large impact on conformation and lipophilicity motivated us to investigate novel pyran inter-halides [23]. We used a halo-divergent route starting from the known

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• between two divergent lanthipeptide clusters – one represented by lichenicidin and Flv peptides. The other peptide, cellulosin, is located next to belongs to the lichenicidin family. However, it has undergone a significant number of functional mutations. Studying these mutations can provide added data on

• liquenicidin VK21, and as the experimental results confirm, despite the in silico predictions, clostrisin does not form heterocycles. These differences in primary and secondary structure could be responsible for the divergent biological activities we encountered. In silico characterization of the post

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• experimental results, Gulder and co-workers devised a strategy to control the dimerization modes by adjusting the polarity of the organic co-solvent to establish the divergent synthesis of dimeric scaffolds. Indeed, with 20% DMF in the SorbC-catalyzed enzymatic oxidative dearomatization, the Michael addition

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• % yield. Under the same conditions, several primary alcohols were tested and gave good to excellent yields (up to 95%) of the desired products. Various substituted secondary alcohols were also tested, giving the alkylated ketones in yields up to 87% (Scheme 47). Tang and Liu reported the divergent

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• unusual methyl modification at the oxygen atom of the typical succinimide ring, a feature not seen in the structurally similar brocaeloid D. Additionally, shentonin A (1) exhibits a cis relationship between H-3 and H-4, as opposed to the trans configuration in brocaeloid D, suggesting a divergent

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• with alkene but also the urea carbonyl. The Bronsted acidity of the urea would be increased by coordination to gold, and if such coordination is key to enabling reactivity, this would confirm the higher reactivity of urea 1a. The divergent behavior of sulfonamide 1d does not find an easy explanation

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• , by extension, common folds [12]. Still, shared binding specificity does not always follow from structural similarity, exemplified by divergent evolution within lectin families as well as independent emergence of similar binding patterns [13]. Many of the most commonly used lectins for the