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

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• inextricably linked to organic chemistry. However, the two fields took divergent paths over the past century. Many emergent radical chemistries in the organic chemistry community has not yet found a place in the polymer science. We believe this gap will narrow with a broader use of chemical informatics tools

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• applied cell potential. These divergent reactivity features make the two techniques totally complementary, allowing the exploration of a large portion of SET-driven organic transformations using at least one of them at a time. Since ‘radical ion’ conPET/e-PRC are proposed to involve the same radical ion

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• stereocenter bearing primary amine and trifluoromethyl functionalities associated with appreciable enantiocontrol. The substrate scope was investigated by the variation of sterically and electronically divergent aryl substituents in the ketimines but the enantioselectivity was markedly lowered with sterically

• output of the reaction furnishing the products with moderate to excellent enantioselectivities. Electronically and sterically divergent functionalities in the benzene ring of 49 expanded the substrate scope whereas variation of 115 was very much limited (Scheme 27) [57]. In 2021, Wang and co-workers

• nitrogen and ring nitrogen of 49 were screened under optimal reaction conditions where Cbz and benzyl were the best protecting groups in terms of enantioselectivities. A product library was prepared by varying sterically and electronic divergent functionalities in the carbocyclic rings of both reactants

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• final Mizoroki–Heck reaction will be discussed in the following section. The Buchwald group [59] reported a ligand-controlled divergent synthesis involving intramolecular cyclisation, allowing for the formation of several heterocycles, including dibenzo[b,f]azepines 89, in two steps. Screening of

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• ) [69]. Through a divergent synthetic route, employing as main steps the formation of the diaryl ether through SNAr-type reactions and the macrolide formation using the Mitsunobu reaction, Kim and co-workers [71] synthesized isocorniculatolide B and corniculatolides B and C for further evaluation of

• synthesis of combretastatin D-2 (2) by Rychnovsky and Hwang [36]. Divergent synthesis of (±)-1 form combretastatin D-2 (2) by Rychnovsky and Hwang [36]. Enantioselective synthesis of 1 by Rychnovsky and Hwang employing Jacobsen catalyst [41]. Synthesis of fragment 57 by Couladouros and co-workers [43][45

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• recently, the same group developed an efficient Rh(III)-catalyzed C–H cross-coupling of enaminones with diazodicarbonyls for the divergent construction of isocoumarins and naphthalenes [27]. Moreover, Loh et al. disclosed a Rh-catalyzed formal [4 + 2] cycloaddition of enaminones with diazocarbonyls [28

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• in our hands, in some cases giving widely divergent chemical shifts for the two chemically equivalent phosphorus atoms, which could potentially exacerbate any deviations from the experimental chemical shifts. Since derivatives with methyl (1a) and butyl substitution on PA were reported and had

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• of atom economy and protecting-group-free synthesis dominating the field of total synthesis. In this new era, total synthesis is moving towards natural efficacy by utilizing both the biosynthetic knowledge of divergent synthesis and the latest developments in radical chemistry. This contemporary

• ” [8]. And this is where divergent total synthesis might help. Divergent total synthesis is an old but yet underdeveloped strategy, utilizing the conceptual advantages of biosynthetic routes that allow multi-target natural product synthesis through a unified synthetic plan [9][10]. Based on the logic

• of divergent synthesis, common synthetic scaffolds, which are regarded as the points of diversity of the synthetic plan, lie at the heart of retrosynthetic design. Radical disconnections on common scaffolds, in accordance to the trends of green chemistry [11] and the concepts of atom economy [12] and

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• derived from a common biosynthetic pathway starting from farnesyl pyrophosphate and glycine [5]. This prompted us to investigate a biomimetic synthesis in which the halichonic acids could be prepared from a common imine intermediate via divergent intramolecular aza-Prins cyclizations [8]. Herein, we

• acyclic conformational analysis. Three divergent mechanistic pathways can be formulated by considering the different conformers of protonated imine 7, namely iminium ions 12a–c (Scheme 3). In each case, the chair-like transition state of the intramolecular aza-Prins reaction is controlled by the C7

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• 402160, China 10.3762/bjoc.17.193 Abstract Chemoselective sulfonylation and isonitrilation reactions for the divergent synthesis of valuable diarylmethyl sulfones and isonitrile diarylmethanes starting from easy-to-synthesize para-quinone methides (p-QMs) and commercially abundant p

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• pyridylic C(sp3)–H bond (Scheme 1b). For examples, Tunge et al. developed a Pd-catalyzed intramolecular decarboxylative coupling of heterocyclic ally esters via a tandem allylation/Cope rearrangement strategy [18]; Hartwig and co-workers reported a stereo-divergent allylic substitution with azaarene