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Search for "resistance" in Full Text gives 343 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies
- Antonio Angelastro,
- Jonathan Bargh,
- Subhajit Guria,
- Victor Laserna and
- Louis Luk
Beilstein J. Org. Chem. 2026, 22, 857–881, doi:10.3762/bjoc.22.67
- overcome resistance, highlighting the need for complementary site-specific antibody labelling strategies. Meanwhile, advances in high-throughput screening and AI-guided design have been creating new scaffolds, including nanobodies, de novo binders and peptoids, where tailored modification chemistries have
Graphical Abstract
Scheme 1: a) Sanger’s reagent (1), b) reductive amination by sodium cyanoborohydride, c) native chemical liga...
Scheme 2: Introduction of carbonyl functionality at protein N-termini via a) oxidation by periodate, b) Rapop...
Scheme 3: a) Concept of disulfide rebridging. Reagents include b) sulfones 6, c) dihaloacetones 7, d) dibromo...
Scheme 4: Multi-disulfide rebridging technologies.
Scheme 5: Formation of full- and half-antibody as a result of disulfide rebridging.
Scheme 6: Use of 2,3-diaminopropionic acid (DAP, 13) for native-sequence substrate profiling.
Scheme 7: Affinity-guided labelling. a) Reagents and catalysts appended to the binder include electrophilic m...
Scheme 8: Chemical sequence to convert subtilisin serine residue into a cysteine analogue.
Scheme 9: Examples of small molecule reagents. Modifications of a–c) methionine by oxaziridine 22, hypervalen...
Scheme 10: Labelling of arginine by reagents carrying a) glyoxal 27, b) phenanthrenequinones 28, c) DKPA 29 gr...
Scheme 11: Examples of linchpin-directed modification targeting a) histidine, b) aspartic acid, and c) lysine ...
Scheme 12: Overview of glycan-directed strategies for site-specific protein modification. a) Structural motifs...
Scheme 13: Generic reaction mechanisms recruited by various native-sequence modifying enzymes.
Scheme 14: a,b) Engineered biocatalysts including sortase. Proteins AGA1 and AGA2 are surface proteins natural...
Scheme 15: Engineered biocatalysts include a) microbial transglutaminase (MTG) and b) penicillin G acylase (PG...
Scheme 16: Selection scheme of a suitable native-sequence labelling tool.
The trans-influence in gold chemistry from a catalytic perspective
- Manfred Bochmann
Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66
- -elimination and chain walking make it necessary to invoke a hypothetical dicationic hydride intermediate, [(P^N)AuH(alkene)]2+. Based on the chemistry of the gold(III) hydrides described above, none of which showed any tendency for migratory alkene insertion [14], and in view of the resistance even of
Graphical Abstract
Scheme 1: Assessment of ligand influence by kinetic competition experiments.
Scheme 2: Ligand types employed in the stabilisation of gold(III) complexes.
Scheme 3: Au(III) π- and σ-complexes stabilised by C^N^C and C^N chelate ligands [28-32] and an example of a gold(II...
Scheme 4: Gold(III) C^C chelate complexes.
Figure 1: Examples of photoemissive gold(III) pyrazine complexes. Dr. J. Fernandez-Cestau is gratefully ackno...
Scheme 5: Gold hydride complexes supported by tridentate pincer ligands and corresponding1H NMR chemical shif...
Scheme 6: Gold(III) hydride formation by oxygen transfer.
Scheme 7: Heterolytic H–H bond cleavage by cationic Au(III) complexes [32,56].
Scheme 8: Gold(III) models of the water-gas shift reaction [30].
Scheme 9: Gold(III) hydride complexes supported by C^C and C^N chelate ligands [32,50].
Scheme 10: O2 insertions into Au–H bonds.
Scheme 11: Alkyne, alkene and isocyanide hydroauration by a bimolecular gold radical mechanism [49,65,66].
Scheme 12: Reactions of (C^C)Au–H with DMAD [50].
Scheme 13: Alkyne hydroauration by a bimolecular Au(III)–Au(I)-assisted process [69].
Scheme 14: Gold(III) π-allyl complexes.
Scheme 15: Outer-sphere mechanism of ethylene insertion into Au–O bonds [20,84].
Scheme 16: Catalytic acetylene functionalisation [86,87].
Scheme 17: Examples of alkene insertions into Au–C bonds [88,89].
Scheme 18: Examples of β-H elimination and chain walking processes in (C^P)-ligated gold alkyls [90].
Scheme 19: Mechanism of alkyne hydroarylation with (C^P) gold catalysts [92].
Scheme 20: Vinylic triflate esters by gold-catalysed nucleophilic attack on alkynes [94].
Scheme 21: Gold-catalysed and gold-free steps in the formation of Heck-type olefins [97,99].
Unsymmetrical sulfoxides with sterically hindered catechol fragment: synthesis, structure, electrochemical properties, and antiradical activity
- Daria A. Burmistrova,
- Vasiliy A. Fokin,
- Oleg P. Demidov,
- Mikhail A. Kiskin,
- Maxim V. Arsenyev,
- Andrey I. Poddel’sky,
- Nadezhda T. Berberova and
- Ivan V. Smolyaninov
Beilstein J. Org. Chem. 2026, 22, 828–837, doi:10.3762/bjoc.22.65
- , imparting resistance to various solvents [9][10]. Furthermore, catechol-containing compounds can serve as antioxidant biomimetic additives in lubricants [11]. One effective approach for the fine-tuning of polyphenol properties is functionalization via the introduction of heteroatoms (S, Se, Te) [12][13][14
Graphical Abstract
Scheme 1: Synthesis of catechol-contained thioethers 1–7 and sulfoxides 1a–7a.
Figure 1: Molecular structures of 1a (a), 4a (b), 5a (c), 6a (d), 7a (e) (solvent molecules and fragment diso...
Figure 2: CV curves of 1 and 1a at the potential ranges: from −0.5 to 1.75 V for 1 (curve 1); from −0.5 to 1....
Scheme 2: Proposed mechanism of electrochemical transformations of catechol sulfoxides (path a – for 1a, 3a, ...
Figure 3: CV curve of 5a at the potential range from −0.50 to 1.40 V (curve 1); from −0.50 to 1.70 V (curve 2...
Figure 4: CV curves of electrolysis products of 7a at the potential ranges from 0.5 to −0.4 V (CH3CN, GC elec...
Scheme 3: Proposed mechanism of the reduction of electrogenerated o-benzoquinone.
Total synthesis of the capsular polysaccharide repeating unit towards the development of a glycoconjugate vaccine against Klebsiella pneumoniae ST512
- Shuo Zhang,
- Ondřej Daněk and
- Peter H. Seeberger
Beilstein J. Org. Chem. 2026, 22, 821–827, doi:10.3762/bjoc.22.64
- leading cause of nosocomial infections, characterized by high morbidity and an escalating degree of antimicrobial resistance [5][6][7][8]. This bacterium is frequently responsible for severe clinical conditions, including urinary tract infections, pneumonia, and septicemia [9][10]. The increasing
Graphical Abstract
Figure 1: Structure of the K. pneumoniae ST512 CPS repeating unit and retrosynthetic analysis.
Scheme 1: Preparation of building blocks 1–4.
Scheme 2: Synthesis of hexasaccharide repeating unit 20.
Scheme 3: Synthesis of the analogues 21–24.
Halogenated azobenzene acrylates: from efficient solution photoswitching to stable solid-state photochromic materials
- Martina Vachtlová,
- Michaela Fecková,
- Vítězslav Zima,
- Jan Podlesný,
- Milan Klikar,
- Oldřich Pytela,
- Patrik Pařík,
- Jakub Opršal,
- Eliška Juhaňáková,
- Veronika Chrtová and
- Filip Bureš
Beilstein J. Org. Chem. 2026, 22, 782–794, doi:10.3762/bjoc.22.60
- analogous comparison using UV–vis absorption spectra along with a fatigue resistance verification. Representative thermal kinetic curves obtained by both UV–vis absorption and 1H NMR spectroscopy are shown in Figure 9. Thermal kinetics were optimized using the OPstat 6.10 software [33]. See Supporting
- contrasts the value found by UV–vis measurement (E/Z = 8:92). The fatigue resistance of compounds 1a–f (Figure 8B) was verified by ten consecutive 355/430 nm switching cycles revealing no structural degradation and photobleaching. Azobenzene monomers 1a–f were further incorporated into a thin polystyrene
- absorption spectra of azobenzene 1e corresponding to the dark-adapted PSS (black), 355 nm-adapted PSS (violet), and 430 nm-adapted PSS (blue) measured in DCE at c = 4 × 10−5 M (20 °C). B) Fatigue resistance of azobenzene 1e verified by ten consecutive 355/430 nm switching cycles. A) Thermal kinetics curve of
Graphical Abstract
Figure 1: Molecular structure of investigated compounds 1a–f and known azobenzene derivatives A–C exploited i...
Scheme 1: Synthesis of azobenzene-acrylate monomers 1a–f.
Figure 2: Representative TGA (left) and DSC (right) curves of compounds 1c (black) and 1d (red).
Figure 3: Energy level diagram of the electrochemically measured (black) and DFT-calculated (red for E-isomer...
Figure 4: A) Experimentally measured UV–vis absorption spectra of the monosubstituted azobenzenes 1a, c and e...
Figure 5: A) Experimentally measured UV–vis absorption spectra of the azobenzenes 1c and 1d at c = 4 × 10−5 M...
Figure 6: A) HOMO/LUMO localizations in representative E-1a. B) HOMO−1/LUMO localizations in representative Z-...
Figure 7: 1H NMR spectra (500 MHz, CDCl3, 20 °C) of azobenzene 1e corresponding to the dark-adapted PSS (blac...
Figure 8: A) UV–vis absorption spectra of azobenzene 1e corresponding to the dark-adapted PSS (black), 355 nm...
Figure 9: A) Thermal kinetics curve of compound 1e obtained by UV–vis monitoring at c = 4 × 10−5 M (DCE, 60 °...
Figure 10: Photoswitching of target azobenzene 1a in the solid state (polymeric matrix). A) Polystyrene thin f...
Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators
- Xi Zhang,
- Jingyan Wang,
- Ziqiang Zhao,
- Caiyi Wang,
- Zenghui Ye,
- Wei-Yuan Ma,
- Jian-Xing Xu and
- Fengzhi Zhang
Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59
- of insulin resistance, inflammation, and hepatic steatosis [15]. The most advanced ASK1 inhibitor in clinical development is the compound celonsertib (Scheme 2). Following this, a series of new ASK1 inhibitors were derived using selonsertib as a lead compound in a variety of structure-optimized ways
Graphical Abstract
Scheme 1: Steroidal and nonsteroidal FXR agonists.
Scheme 2: ASK1 inhibitors.
Scheme 3: Dual FXR/ASK1 modulation strategy for MASH.
Scheme 4: Synthesis of compound 2. Conditions: (a) NH2OH·HCl, NaOH, EtOH/H2O, 70 °C, 12 h; (b) NCS, DMF, 40 °...
Scheme 5: Synthesis of compounds IXa–d. Conditions: (a) N2H4·H2O, MeOH, rt, 12 h; (b) DMF–DMA, 80 °C, 12 h; (...
Scheme 6: Synthesis of compounds Z1–15. Conditions: (a) K2CO3, KI, MeCN, 50 °C, 6 h, 86–96% yield; (b) Pd2(db...
Scheme 7: Synthesis of compounds Z16–29. Conditions: (a) Pd(PPh3)4, Na2CO3, 1,4-dioxane/H2O, 80 °C, 18 h, 64–...
Scheme 8: Synthesis of compound Z30. Conditions: (a) NaH, DMF, rt, 16 h; (b) TFA, DCM, 0 °C, 3 h; (c) Pd2(dba)...
Scheme 9: Molecular docking of dual-target modulator Z8 to the ligand binding sites of FXR (PDB ID: 3DCT, htt...
Figure 1: FXR agonist activity of all compounds. Results of the dual-luciferase reporter assay in CHO cells c...
Figure 2: ASK1 inhibition of all compounds. Results of the ADP-Glo™ kinase assay after treating ASK1 kinase w...
Figure 3: Effects of Z8 and Z30 on OA-induced lipid accumulation in HepG2 cells. Cells were treated with GW40...
Advantages of PROTACs in achieving selective degradation of homologous protein families
- Luxi Yang,
- Xinfei Mao,
- Jingyi Zhang,
- Jing Shu,
- Wenhai Huang,
- Xiaowu Dong,
- Yinqiao Chen and
- Mingfei Wu
Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49
- resistance [61]. Although many small-molecule inhibitors have also been developed for CDK9 so far, due to the high homology of the CDK family, inhibitors always tend to target a variety of CDK members, thereby reducing their specificity as therapeutic agents and chemical probes and results in many adverse
- proliferation [125]. Because long-term treatment with imatinib will lead to drug resistance in CML patients, the second generation of TKI was subsequently developed for treatment [129]. Although TKIs targeting BCR-ABL have achieved significant therapeutic effects, CML patients often need to take such drugs for
- : Serum-glucocorticoid-induced protein kinase (SGK) plays a key role in mediating resistance to phosphoinositide 3-kinase (PI3K)/Akt inhibition in breast cancer cells [132]. It has been reported that different ATP competitive inhibitors have similar affinity for all SGK isoforms [133][134]. Due to the
Graphical Abstract
Figure 1: Mechanism of a PROTAC-mediated targeted protein degradation. Created in BioRender. Wu, M. (2026) ht...
Figure 2: CDK4/6 PROTACs with alkyl or PEG chains as linkers.
Figure 3: CDK4/6 PROTACs with triazole-containing linkers.
Figure 4: Structures of AT-7519 (7) and FN-1501 (8), and CDK9 degrading PROTACs based on compound 8 with vari...
Figure 5: CDK9 PROTACs with alkane chain as linkers or triazole linkers.
Figure 6: Structures of HDAC6 inhibitors ACY1215 (17) and ACY-241 (18), as well as the structure of PROTACs 1...
Figure 7: C4-linked-series and C5-linked-series of HDAC6 PROTACs.
Figure 8: Structures of VHL-based degraders.
Figure 9: Structures of VHL-based and CRBN-based selective HDAC PROTACs.
Figure 10: Structures of the “amide series” and “phenyl series” PROTACs studied by Crews et al.
Figure 11: Structures of the “amide series” PROTACs.
Figure 12: Structures of the “phenyl series” PROTACs.
Figure 13: Structures of JQ1 (34) and MZ1 (35).
Figure 14: Structures of macro-PROTAC-1 and SHD913.
Figure 15: Commonly utilized thalidomide-derived CRBN ligands and possible linker attachment styles. A1, A2: p...
Figure 16: VHL ligands frequently used in PROTACs. Linker attachment options are represented with curly bonds ...
Figure 17: Varying the inhibitor warhead and the recruited E3 ligase permits targets to be accessed for degrad...
Figure 18: Structures of YX-2-233 (42) and YX-2-107 (43).
Figure 19: Structures of compounds 44 and 45.
Figure 20: Design of the SGK3 PROTACs.
Figure 21: CRBN, VHL, and IAP ligands used when designing HDAC-PROTACs.
Figure 22: CDK4/6-PROTACs with different E3 ligands targeting the same E3 ubiquitin ligase.
Figure 23: Structural basis for the selective degradation of CDK6 over CDK4 by PROTAC 2. (A) CDK4–molecule 2–C...
Figure 24: Regarding the PPI-driven selectivity mechanism of two PROTAC molecules, SJF-α and SJF-δ, for p38α a...
Figure 25: Co-crystal structure and ultra-high selectivity of the STAT6 PROTAC degrader AK-1690. (A) STAT6–AK-...
Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs
- Sophie Day-Riley,
- Sona Krajcovicova,
- Aryaman Raj Sokhal,
- Jan L. Venne,
- Paul Brear,
- Marko Hyvönen,
- Benjamin C. Whitehurst,
- Jason S. Carroll and
- David R. Spring
Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47
- . Despite successes with ATP-competitive inhibitors, small-molecule kinase inhibitors can be limited by reversible target engagement, off-target effects, and susceptibility to resistance mechanisms [7]. These challenges have motivated the exploration of alternative therapeutic modalities that move beyond
Graphical Abstract
Figure 1: Design strategy and validation. A) Structure of CAM4066 (1) that served as a model design for the d...
Scheme 1: Synthesis of the key ligand-linker PROTAC precursors. For compound 14, HATU/DIPEA has been used ins...
Scheme 2: (A) Synthesis of final VHL PROTACs; (B) Synthesis of final CRBN PROTACs. Abbreviations: Boc = tert-...
Figure 2: Full structures of final VHL PROTACs 23–26 and CRBN PROTACs 28 and 29.
Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity
- Artem S. Sazonov,
- Dmitry A. Vasilenko,
- Denis V. Porfiriev,
- Yuri K. Grishin,
- Rimma A. Gazzaeva,
- Alisa P. Chernyshova,
- Maxim A. Kryakvin,
- Anna A. Baranova,
- Vera A. Alferova and
- Elena B. Averina
Beilstein J. Org. Chem. 2026, 22, 592–602, doi:10.3762/bjoc.22.45
- strategies to combat the antibiotic resistance include, in particular, the synthesis of novel antibacterial agents based on isoxazole derivatives [17]. In this regards, the development of efficient and convenient methods for the sulfonyl-containing isoxazoles synthesis has received great attention. The most
Graphical Abstract
Figure 1: Examples of sulfonylisoxazoles with biological activities.
Scheme 1: Reactions for preparing 5-sulfonylisoxazoles.
Scheme 2: Scope of 5-nitroisoxazoles 1a–g in the reaction with thiophenols.
Scheme 3: Scope of 5-thioisoxazoles 2a-p in the reaction with mCPBA.
Scheme 4: Oxidation of 5-thioisoxazoles into 5-sulfinylisoxazoles.
Figure 2: The samples of isoxazole derivatives trigger SOS response in E. coli reporter strains. A) Agar plat...
Figure 3: Inhibition of Klenow fragment of E. coli DNA polymerase I. A) The principal scheme of the Klenow fr...
Figure 4: Inhibition of E. coli DNA gyrase and Topo IV cleavage activity. A) The principal scheme of E. coli ...
Figure 5: Inhibition of E. coli DNA Topo I cleavage activity. A) The principal scheme of E. coli DNA Topo I c...
Figure 6: Inhibition of E. coli DNA gyrase supercoiling activity. A) The principal scheme of E. coli DNA gyra...
Figure 7: Inhibition of E. coli DNA Topo IV decatenation activity. A) The principal scheme of of E. coli DNA ...
Design and synthesis of an erdafitinib-based selective FGFR2 degrader
- Yumeng Jin,
- Shidong Wang,
- Sihan Pan,
- Shuqi Huang,
- Weichen Zhou,
- Xiaohao Huang,
- Lei Zheng and
- Lingfeng Chen
Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44
- growth factor receptor 2 (FGFR2) to overcome the issues of drug resistance and adverse reactions associated with traditional inhibitors in the treatment of FGFR2-driven tumors. Erdafitinib was employed as the targeting ligand, and its aliphatic amine site was conjugated with a CRBN E3 ligase ligand to
- FGFR2-selective inhibitor, is the first highly selective FGFR2 inhibitor. Although substantial advancements have been made in developing FGFR2-targeted therapeutics, the sustained clinical efficacy of these inhibitors in oncology remains constrained by the emergence of acquired resistance mechanisms
- signaling pathway [35][36]. These advances have driven the development of several selective FGFR2 inhibitors, including erdafitinib, infiglatinib, and FGF401 [37][38][39]. However, issues such as acquired drug resistance and on-target toxicity emerging in clinical applications have limited the long-term
Graphical Abstract
Figure 1: Chemical structures of severel FGFR inhibitors and degraders.
Figure 2: Rationale of the FGFR2 degrader design. a) Structure of the erdafitinib–FGFR complex. The figure wa...
Scheme 1: Synthesis of PROTACs towards FGFR2. Reagents and conditions: (a) K2CO3, Pd (dppf)Cl2, 1,4-dioxane/H2...
Figure 3: a) Representative western blots evaluating the total FGFR2 levels in KATO III cells following treat...
Figure 4: a) FGFR1, FGFR2, FGFR3, and FGFR4 levels in cells after treatment. b) The mechanism of PROTAC. It w...
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
- enhances its therapeutic efficacy but also helps in overcoming resistance mechanisms that limit the effectiveness of other microtubule-targeting agents. Research continues to explore additional applications of 1 in various cancer types, including non-small cell lung cancer, ovarian cancer, and other soft
Graphical Abstract
Figure 1: Eribulin with common synthetic precursor fragments and halichondrin B.
Scheme 1: Overview of the industrial process pathway for the large-scale production of the mesylate salt of 1...
Scheme 2: Synthesis of 22. (a) i. 2,2-dimethoxypropane, p-TsOH, MeOH, 65 °C; ii. NaBH4, MeOH, rt; (b) i. NaH,...
Scheme 3: Synthesis of 27. (a) i. NaH, BnBr, THF, rt; ii. iodobenzoic acid, MeCN, 80 °C; iii. (EtO)2POCH2COOE...
Scheme 4: Synthesis of 31 and 33. (a) i. MMTrCl, iPr2NEt, DCM, rt; ii. K2CO3, MeOH, DCM, rt; iii. TBDMSCl, im...
Scheme 5: Synthesis of 1. (a) CrCl2, 37, 38, 39 (proton sponge), LiCl, Mn, ZrCp2Cl2, MeCN, EtOAc; (b) SrCO3, t...
Scheme 6: Synthesis of 45. Above: Reaction conditions: (a) methoxyacetic acid, BF3·OEt2, DCM, −30 °C; (b) Pd(...
Scheme 7: Synthesis of 64. Reaction conditions: (a) i. acetone, I2, rt; ii. vinylmagnesium bromide, THF, −20 ...
Scheme 8: Synthesis of 79. Above: Reaction conditions: (a) i. K2CO3, MeOH, 60 °C; ii. 2,2-dimethoxypropane, H2...
Scheme 9: Synthesis of 92. Reaction conditions: (a) TESCl, imidazole, DCM, 0 °C to rt; (b) i. oxalyl chloride...
Scheme 10: Synthesis of 104. Above: Reaction conditions: (a) cyclohexanone, p-TsOH, toluene, 110 °C, crystalli...
Scheme 11: Synthesis of 117. (a) i. acetone, CuSO4, rt; ii. H2O2, K2CO3, H2O, rt; iii. EtI, MeCN, 70 °C; (b) i...
Scheme 12: Synthesis of 121. Reaction conditions: (a) i. TBDPSCl, imidazole, DMF, rt; ii. O3, DCM, −78 °C; iii...
Scheme 13: Synthesis of 131. (a) i. 2,2-dimethoxypropane, p-TsOH, MeOH, 60 °C; ii. LiAlH4, THF, 0 °C to rt; (b...
Scheme 14: Synthesis of 143. (a) i. I2, PPh3, imidazole, DCM; ii. HMPA, CuI, vinylmagnesium bromide, THF, −20 ...
Scheme 15: Modified synthesis of 104. Reaction conditions: (a) (EtO)2POCH2COOEt, KOt-Bu, THF, 15 °C; (b) TBAF,...
Scheme 16: Synthesis of 161. Reaction conditions: (a) crotyl bromide, Sn, TBAI, NaI, DMF/H2O, rt; (b) NaH, BnB...
Scheme 17: Synthesis of 169. Reaction conditions: (a) i. Co2(CO)8, BF3·Et2O, DCM, 23 °C; ii. CAN, acetone, 0 °...
Scheme 18: Synthesis of 181. Reaction conditions: (a) i. Co2(CO)8, BF3·Et2O, DCM, 23 °C; ii. (NH4)2Ce(NO3)6, a...
Scheme 19: Synthesis of 186. Reaction conditions: (a) NEt3, LiCl, MeCN, 0–23 °C; (b) HF·pyridine, MeCN, 23 °C;...
Scheme 20: Modified synthesis of 181. Reaction conditions: (a) i. Ni(cod)2, P(n-Bu)3, Et3SiH, THF, 23 °C; ii. ...
Scheme 21: Synthesis of 200. Reaction conditions: (a) i. Co2(CO)8, DCM, 23 °C; ii. BF3·Et2O, 0 °C; iii. (NH4)2...
Scheme 22: Modified synthesis of 186. Reaction conditions: (a) DDQ, 2,6-di-t-Bu-4-hydroxytoluene, hv, MeCN, 23...
Scheme 23: Synthesis of 1. Reaction conditions: (a) i. CrCl2, NiCl2, 206, NEt3, THF, 23 °C; ii. DBU, toluene, ...
Scheme 24: Synthesis of 217. Above: Reaction conditions: (a) TBDPSCl, imidazole, DCM, 0–5 °C. (b) m-CPBA, DCM,...
Scheme 25: Synthesis of 231. Reaction conditions: (a) i. AcCl, MeOH, 0 °C to rt; ii. TrCl, pyridine, 50 °C; (b...
Scheme 26: Synthesis of 239. Reaction conditions: (a) i. Boc2O, K2CO3, THF, rt; ii. Ru(acac)3, NaBrO3, EtOAc, H...
Scheme 27: Synthesis of 247. Reaction conditions: (a) NCS, 248, MeCN, 0 °C to rt; (b) LDA, 249, THF, −78 °C; (...
Scheme 28: Synthesis of 255. Reaction conditions: (a) i. LiHMDS, THF, −78 °C to rt; ii. m-CPBA, DCM, −78 °C to...
Scheme 29: Synthesis of 261. Reaction conditions: (a) allyltrimethylsilane, TiCl4, DCM −78 °C; (b) LiBH4, EtOH...
Scheme 30: Synthesis of 265. Reaction conditions: (a) (R,R)-Ru-cat (0.2 mol %), DCM, NEt3, HCOOH, rt; (b) TBAF...
Scheme 31: Synthesis of 272. Reaction conditions: (a) LDA, THF, −78 °C; (b) DMP, NaHCO3, DCM, 0 °C to rt; (c) (...
Scheme 32: Synthesis of 292. Reaction conditions: (a) TsCl, NEt3, DCM, rt; (b) K2CO3, MeOH, 45 °C; (c) vinylma...
Scheme 33: Synthesis of 296. Reaction conditions: (a) 171 (see Scheme 17), Cr-cat, CoPc (see Scheme 17), Mn, NEt3·HCl, LiCl, TMS...
Scheme 34: Synthesis of 299. Reaction conditions: (a) 172 (see Scheme 17), CrCl2, NEt3, NiCl2, THF, rt; (b) KHMDS, THF,...
Scheme 35: Synthesis of 305. Reaction conditions: (a) i. p-TsOH, MeOH, 40 °C; ii. MeLi, LiBr, THF, −25 °C; (b)...
Scheme 36: Synthesis of 1. Reaction conditions: (a) i. 41 (see Scheme 6), LDA, THF, −78 °C; ii. DMP, NaHCO3, DCM, rt; ...
Scheme 37: Synthesis of 324. Reaction conditions: (a) i. acetone, CuSO4, rt; ii. H2O2 (30%), K2CO3, rt; iii. E...
Synthesis of diaryl phosphates using phytic acid as a phosphorus source
- Kazuya Asao,
- Seika Matsumoto,
- Haruka Mori,
- Riku Yoshimura,
- Takeshi Sasaki,
- Naoya Hirata,
- Yasuyuki Hayakawa and
- Shin-ichi Kawaguchi
Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15
- hydrolysis of phytic acid without phytases is extremely difficult because of its hydrolysis resistance, and only a few studies have considered the utilization of phytic acid as a phosphorus source [6]. In recent years, industrial applications of phytic acid have been investigated for its potential
Graphical Abstract
Scheme 1: Structure of phytic acid.
Figure 1: Structures of representative phosphate esters.
Figure 2: Synthetic methods for phosphorus compounds bypassing white phosphorus or phosphorus chloride.
Figure 3: Conditions for the syntheses of diaryl phosphates using phytic acid as a phosphorus source and scop...
Scheme 2: Phosphoric acid diesterification reaction conducted in a previous study.
Scheme 3: Scale-up reaction conducted for the time-course analysis of phosphate esterification. The reaction ...
Figure 4: Time-course analysis plots of the diphenylphosphate formation from phytic acid and 1a. The beginnin...
Figure 5: A possible reaction pathway for the formation of phosphate ester using phytic acid as the phosphoru...
Figure 6: 31P NMR spectrum of phytic acid extracted from rice bran.
Scheme 4: Esterification reaction conditions using the extracted phytic acid. The yield refers to the isolate...
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
- dehydrogenase type 1 (11-β-HSD-1), a key enzyme that alleviates insulin resistance by lowering cortisol production. Compound 157 emerged as a promising 11-β-HSD-1 inhibitor candidate. In 2016, researchers from Boehringer Ingelheim Pharmaceuticals and the University of Pennsylvania reported a concise and
Graphical Abstract
Scheme 1: The association between dearomatization and natural product synthesis.
Scheme 2: Key challenges in hydrogenation of aromatic rings.
Scheme 3: Hydrogenation of heterocyclic aromatic rings.
Scheme 4: Hydrogenation of the carbocyclic aromatic rings.
Scheme 5: Hydrogenation of the heterocycle part in bicyclic aromatic rings.
Scheme 6: Hydrogenation of the heterocycle part in bicyclic aromatic rings.
Scheme 7: Hydrogenation of benzofuran, indole, and their analogues.
Scheme 8: Hydrogenation of benzofuran, indole, and their analogues.
Scheme 9: Total synthesis of (±)-keramaphidin B by Baldwin and co-workers.
Scheme 10: Total synthesis of (±)-LSD by Vollhardt and co-workers.
Scheme 11: Total synthesis of (±)-dihydrolysergic acid by Boger and co-workers.
Scheme 12: Total synthesis of (±)-lysergic acid by Smith and co-workers.
Scheme 13: Hydrogenation of (−)-tabersonine to (−)-decahydrotabersonine by Catherine Dacquet and co-workers.
Scheme 14: Total synthesis of (±)-nominine by Natsume and co-workers.
Scheme 15: Total synthesis of (+)-nominine by Gin and co-workers.
Scheme 16: Total synthesis of (±)-lemonomycinone and (±)-renieramycin by Magnus.
Scheme 17: Total synthesis of GB13 by Sarpong and co-workers.
Scheme 18: Total synthesis of GB13 by Shenvi and co-workers.
Scheme 19: Total synthesis of (±)-corynoxine and (±)-corynoxine B by Xia and co-workers.
Scheme 20: Total synthesis of (+)-serratezomine E and the putative structure of huperzine N by Bonjoch and co-...
Scheme 21: Total synthesis of (±)-serralongamine A and the revised structure of huperzine N and N-epi-huperzin...
Scheme 22: Early attempts to indenopiperidine core.
Scheme 23: Homogeneous hydrogenation and completion of the synthesis.
Scheme 24: Total synthesis of jorunnamycin A and jorumycin by Stoltz and co-workers.
Scheme 25: Early attempt towards (−)-finerenone by Aggarwal and co-workers.
Scheme 26: Enantioselective synthesis towards (−)-finerenone.
Scheme 27: Total synthesis of (+)-N-methylaspidospermidine by Smith, Grigolo and co-workers.
Scheme 28: Dearomatization approach towards matrine-type alkaloids.
Scheme 29: Asymmetric total synthesis to (−)-senepodine F via an asymmetric hydrogenation of pyridine.
Scheme 30: Selective hydrogenation of indole derivatives and application.
Scheme 31: Synthetic approaches to the oxindole alkaloids by Qi and co-workers.
Scheme 32: Total synthesis of annotinolide B by Smith and co-workers.
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
- properties [1]. Among its notable physical attributes is its high corrosion resistance: metallic zirconium is exceptionally stable toward acids and bases at ambient temperature and is less susceptible to corrosion than titanium. Its low toxicity and excellent biocompatibility have historically supported the
Graphical Abstract
Figure 1: Historical background of zirconium and its physical properties. Image depicted in the background of ...
Scheme 1: Zr-mediated radical cyclization.
Scheme 2: Ni/Zr-mediated one-pot ketone synthesis.
Scheme 3: Zirconocene-catalyzed alkylative dimerization of 2-methylene-1,3-dithiane.
Scheme 4: Zirconium complexes as a photoredox catalyst.
Scheme 5: Zr-catalyzed reductive ring opening of epoxides.
Scheme 6: Zr-catalyzed reductive ring opening of oxetanes. a10 mol % of Cp2Zr(OTf)2·THF was used. bPhCF3 was ...
Scheme 7: Zr-catalyzed halogen atom transfer of alkyl chlorides.
Scheme 8: Zr-catalyzed radical homo coupling of alkyl chlorides.
Scheme 9: Zr-catalyzed fluorine atom transfer.
Scheme 10: Zr-catalyzed C–O bond cleavage. aYield without the use of P(OEt)3.
Scheme 11: Application to the total synthesis of halichondrins.
Scheme 12: Zr-catalyzed C3 dimerization of 3-bromotryptophan derivatives. aCp2ZrCl2 was used.
Scheme 13: Mechanistic studies.
Scheme 14: Application to the total synthesis of cyctetryptomycins. A photo of compound 61b was taken by the a...
Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition
- Yilin Liu,
- Yuchen Yang,
- Chen Yang,
- Sha-Hua Huang,
- Jian Jin and
- Ran Hong
Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196
- biological agents has led to a rapid emergence of resistance, which in turn diminishes the national-wide and even global-wide food security. Moreover, toxins produced by fungi in diseased crops have serious impacts on animal and human health [2]. There remains high demand to develop new antifungal compounds
- action may not be consistent with those of known fungicide classes. This encouraging characteristic indicates its potential to overcome resistance to other fungicides [6][7][8]. Structurally, malayamycin A belongs to a class of modified nucleosides that mimic UDP (uridine 5′-diphosphate)-linked
Graphical Abstract
Figure 1: Selected natural uracil-containing nucleosides (the key perhydrofuropyran core highlighted in blue)....
Scheme 1: Synthetic strategies toward malayamycin A. (A) Previous synthetic route. (B) Our strategy toward th...
Scheme 2: Rational for intramolecular dipolar cycloaddition.
Scheme 3: Proposed pathway for the enone formation.
Scheme 4: Modified route to access the core of malayamycins.
Scheme 5: Attempting the Baeyer–Villiger reaction.
Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity
- Giuseppe Granata,
- Loredana Ferreri,
- Claudia Giovanna Leotta,
- Giovanni Mario Pitari and
- Grazia Maria Letizia Consoli
Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195
- represents a promising approach to overcoming several limitations associated with traditional monovalent therapeutics, including drug resistance, off-target effects, high dosage requirements, and insufficient specificity. This strategy may pave the way for next-generation anticancer therapies more effective
Graphical Abstract
Scheme 1: Procedure for the synthesis of compound 3.
Figure 1: 1H NMR (left) and 13C NMR (right) spectra of compound 3 in DMSO-d6 (400.13 MHz, 297 K).
Figure 2: Intensity-weighted mean hydrodynamic diameter (left), and zeta potential distribution (right) of co...
Figure 3: Antiproliferative effects by compound 3 and its chemical precursor 1. A) Results on proliferative k...
Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications
- Jullyane Emi Matsushima,
- Khushbu,
- Zuliah Abdulsalam,
- Udyogi Navodya Kulathilaka Conthagamage and
- Víctor García-López
Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179
- proximity to the fluorescent stopper. The reported findings involving dithienylethene-based rotaxanes prove their promising future in materials applications, mainly due to their high photofatigue resistance. Spiropyran While most spiropyran-based rotaxanes have the photoswitchable unit located on the axle
Graphical Abstract
Figure 1: Schematic of common rotaxanes (left) and depiction of the macrocycle shuttling (right).
Figure 2: Structure of some common photoswitches integrated into rotaxanes.
Figure 3: Rotaxane with an acridane photoswitch on the axle modulates the translation of a CBQT4+ macrocycle ...
Figure 4: Hydrogel composed of [2]rotaxanes featuring a central azobenzene in the axle and a cyclodextrin mac...
Figure 5: Dendrimer composed of [2]rotaxane with an azobenzene photoswitch functioning as a macroscopic actua...
Figure 6: (a) Structure of the [2]rotaxane and (b) mechanism for K+ cations transport across lipid bilayers. Figure 6...
Figure 7: Dithienylethene-based [2]rotaxane used in writing patterning applications: (a) rotaxane with open d...
Figure 8: Dithienylethene-based [1]rotaxane shuttling motion triggered by pH changes (top). Dithienylethene p...
Figure 9: Depiction of a fumaramide-based [2]rotaxane photoswitching cycle and deposition on glass and mica s...
Figure 10: Hydrazone-based rotaxane controls helical pitch in a liquid crystal. Figure 10 was adapted from [73] (© 2024 S. ...
Figure 11: (a) Light- and pH-responsive Förster resonance energy transfer observed on a spiropyran-based [2]ro...
Figure 12: Photoresponsive bending of artificial muscle with [c2]daisy chain reported by Harada and collaborat...
Figure 13: Light-responsive shuttling motion of [2]rotaxane based on a stiff-stilbene photoswitch. Figure 13 was reprod...
Figure 14: Azobenzene-based rotaxane modulating lipid bilayers upon photoisomerization. Figure 14 was adapted from [23] (© ...
Figure 15: Depiction of fluorescence quenching processes upon external stimuli of a dithienylethene-based [2]r...
Figure 16: Diagrammatic illustration of rotaxane 1-H-SP depicting interconversions between the four isomeric s...
Figure 17: Representation of [2]rotaxane chloride binding modulated by photoisomerization of a stiff-stilbene. ...
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
- sofosbuvir (2). Fluorination at C2 in the nucleoside results in metabolic stability and resistance to hydrolysis as it destabilizes the formation of a C1 oxocarbenium ion [5][6]. Trifluoromethylated γ-butyrolactones also find applications as antiviral agents, for example, lactone 4 which has activity against
Graphical Abstract
Figure 1: Halogen-containing butyrolactone-derived bioactives.
Scheme 1: Preparation of chlorinated and brominated lactones 8a,b and 11a,b.
Scheme 2: Preparation of fluorinated lactone 14.
Scheme 3: Fluorination of LGO (5) and conversion to lactone 17.
Scheme 4: Trifluoromethylation of 9a,b and 15 and subsequent Baeyer–Villiger oxidation.
C2 to C6 biobased carbonyl platforms for fine chemistry
- Jingjing Jiang,
- Muhammad Noman Haider Tariq,
- Florence Popowycz,
- Yanlong Gu and
- Yves Queneau
Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165
- -designed Pd@S-1 and H-beta zeolite catalytic system, exhibiting high resistance to coking in presence of NH3. Subsequent carboxylation with CO2 and hydrogenation over Rh/C as catalyst led to racemic proline, an important precursor for pharmaceuticals, in quantitative yield. ᴅ-Proline was then obtained in
Graphical Abstract
Figure 1: C2–C6 biobased carbonyl building blocks.
Scheme 1: Proposed (2 + 2) route to glycolaldehyde and glycolic acid from erythritol by Cu/AC catalyst (AC = ...
Scheme 2: Reductive amination of GCA.
Scheme 3: N-Formylation of secondary amines by reaction with GCA.
Scheme 4: Synthesis and conversion of hydroxy acetals to cyclic acetals.
Scheme 5: Synthesis of 3-(indol-3-yl)-2,3-dihydrofurans via three-component reaction of glycolaldehyde, indol...
Scheme 6: BiCl3-catalyzed synthesis of benzo[a]carbazoles from 2-arylindoles and α-bromoacetaldehyde ethylene...
Scheme 7: Cu/NCNSs-based conversion of glycerol to glycolic acid and other short biobased acids.
Scheme 8: E. coli-based biotransformation of C1 source molecules (CH4, CO2 and CO) towards C2 glycolic acid.
Scheme 9: N-Formylation of amines with C2 (a) or C3 (b) biomass-based feedstocks.
Scheme 10: Methods for the formation of propanoic acid (PA) from lactic acid (LA).
Scheme 11: Co-polymerization of biobased lactic acid and glycolic acid via a bicatalytic process.
Scheme 12: Oxidation of α-hydroxy acids by tetrachloroaurate(III) in acetic acid–sodium acetate buffer medium.
Figure 2: Selective catalytic pathways for the conversion of lactic acid (LA).
Scheme 13: Synthesis of 1,3-PDO via cross-aldol reaction between formaldehyde and acetaldehyde to 3-hydroxypro...
Scheme 14: Hydrothermal conversion of 1,3-dihydroxy-2-propane and 2,3-dihydroxypropanal to methylglyoxal.
Scheme 15: FLS-catalyzed formose reaction to synthesize GA and DHA.
Scheme 16: GCA and DHA oxidation products of glycerol and isomerization of GCA to DHA under flow conditions us...
Scheme 17: Acid-catalyzed reactions of DHA with alcohols.
Scheme 18: Synthesis of dihydroxyacetone phosphate from dihydroxyacetone.
Scheme 19: Bifunctional acid–base catalyst DHA conversion into lactic acid via pyruvaldehyde or fructose forma...
Scheme 20: Catalytic one-pot synthesis of GA and co-synthesis of formamides and formates from DHA.
Scheme 21: (a) Synthesis of furan derivatives and (b) synthesis of thiophene derivative by cascade [3 + 2] ann...
Scheme 22: Brønsted acidic ionic liquid catalyzed synthesis of benzo[a]carbazole from renewable acetol and 2-p...
Scheme 23: Asymmetric hydrogenation of α-hydroxy ketones to 1,2-diols.
Scheme 24: Synthesis of novel 6-(substituted benzylidene)-2-methylthiazolo [2,3-b]oxazol-5(6H)-one from 1-hydr...
Scheme 25: ʟ-Proline-catalyzed synthesis of anti-diols from hydroxyacetone and aldehydes.
Scheme 26: C–C-bond-formation reactions of a biomass-based feedstock aromatic aldehyde (C5) and hydroxyacetone...
Scheme 27: Ethanol upgrading to C4 bulk chemicals via the thiamine (VB1)-catalyzed acetoin condensation.
Scheme 28: One-pot sequential chemoenzymatic synthesis of 2-aminobutane-1,4-diol and 1,2,4-butanetriol via 1,4...
Scheme 29: Synthesis of 1,4-dihydroxybutan-2-one by microbial transformation.
Scheme 30: Conversion of polyols by [neocuproine)Pd(OAc)]2(OTf)2] to α-hydroxy ketones.
Scheme 31: Chemoselective oxidation of alcohols with chiral palladium-based catalyst 2.
Scheme 32: Electrochemical transformation of furfural to 5-hydroxy-2(5H)-furanone (HFO).
Scheme 33: Selective hydrodeoxygenation of HFO and oxidation to γ-butyrolactone (GBL).
Scheme 34: Photosensitized oxygenation of furan towards HFO via ozonide intermediates.
Scheme 35: Conversion of furfural to HFO and MAN by using mesoporous carbon nitride (SGCN) as photocatalyst.
Scheme 36: Synthesis of HFO from furan derivatives.
Scheme 37: Photooxidation of furfural to 5-hydroxy-2(5H)-furanone (HFO).
Scheme 38: Synthesis of Friedel–Crafts indole adduct from HFO.
Scheme 39: Conversion of HFO to α,γ-substituted chiral γ-lactones.
Scheme 40: Tautomeric transformation of HFO to formylacrylic acid.
Scheme 41: Hydrolysis of HFO to succinic acid in aqueous solution.
Scheme 42: Substitution and condensation reactions of 5-hydroxy-2(5H)-furanone (HFO).
Scheme 43: (a) Conversion of HFO towards valuable C4 chemicals and (b) anodic oxidation of 5-hydroxy-2(5H)-fur...
Figure 3: Conversion of HFO towards other natural and synthetic substances.
Scheme 44: Conversion of furfural to maleic anhydride (reaction a: VOx/Al2O3; reaction b: VPO).
Scheme 45: Conversion of furfural into succinic acid.
Scheme 46: Electro‑, photo‑, and biocatalysis for one-pot selective conversions of furfural into C4 chemicals.
Scheme 47: Production route of furfural from hemicellulose.
Scheme 48: Mechanism for xylose dehydration to furfural through a choline xyloside intermediate.
Scheme 49: Conversion of furfural to furfuryl alcohol and its derivatives.
Scheme 50: Conversion of furfural to furfuryl alcohol and 3-(2-furyl)acrolein.
Scheme 51: The aerobic oxidative condensation of biomass-derived furfural and linear alcohols.
Scheme 52: The single-step synthesis of 2-pentanone from furfural.
Scheme 53: Electrocatalytic coupling reaction of furfural and levulinic acid.
Scheme 54: Conversion of furfural to m-xylylenediamine.
Scheme 55: Conversion of furfural to tetrahydrofuran-derived amines.
Scheme 56: Formation of trans-4,5-diamino-cyclopent-2-enones from furfural.
Scheme 57: Production of pyrrole and proline from furfural.
Scheme 58: Synthesis of 1‑(trifluoromethyl)-8-oxabicyclo[3.2.1]oct-3-en-2-ones from furfural.
Scheme 59: Conversion of furfural to furfural-derived diacids.
Scheme 60: A telescope protocol derived from furfural and glycerol.
Scheme 61: A tandem cyclization of furfural and 5,5-dimethyl-1,3-cyclohexanedione.
Scheme 62: A Ugi four-component reaction to construct furfural-based polyamides.
Scheme 63: One-pot synthesis of γ-acyloxy-Cy7 from furfural.
Scheme 64: Dimerization–Piancatelli sequence toward humins precursors from furfural.
Scheme 65: Conversion of furfural to CPN.
Scheme 66: Synthesis of jet fuels range cycloalkanes from CPN and lignin-derived vanillin.
Scheme 67: Solar-energy-driven synthesis of high-density biofuels from CPN.
Scheme 68: Reductive amination of CPN to cyclopentylamine.
Scheme 69: Asymmetric hydrogenation of C=O bonds of exocyclic α,β-unsaturated cyclopentanones.
Scheme 70: Preparation of levulinic acid via the C5 route (route a) or C6 route (routes b1 and b2).
Scheme 71: Mechanism of the rehydration of HMF to levulinic acid and formic acid.
Scheme 72: Important levulinic acid-derived chemicals.
Scheme 73: Direct conversion of levulinic acid to pentanoic acid.
Scheme 74: Catalytic aerobic oxidation of levulinic acid to citramalic acid.
Scheme 75: Conversion of levulinic acid to 1,4-pentanediol (a) see ref. [236]; b) see ref. [237]; c) see ref. [238]; d) see r...
Scheme 76: Selective production of 2-butanol through hydrogenolysis of levulinic acid.
Scheme 77: General reaction pathways proposed for the formation of 5MPs from levulinic acid.
Scheme 78: Selective reductive amination of levulinic acid to N-substituted pyrroles.
Scheme 79: Reductive amination of levulinic acid to chiral pyrrolidinone.
Scheme 80: Reductive amination of levulinic acid to non-natural chiral γ-amino acid.
Scheme 81: Nitrogen-containing chemicals derived from levulinic acid.
Scheme 82: Preparation of GVL from levulinic acid by dehydration and hydrogenation.
Scheme 83: Ruthenium-catalyzed levulinic acid to chiral γ-valerolactone.
Scheme 84: Catalytic asymmetric hydrogenation of levulinic acid to chiral GVL.
Scheme 85: Three steps synthesis of ε-caprolactam from GVL.
Scheme 86: Multistep synthesis of nylon 6,6 from GVL.
Scheme 87: Preparation of MeGVL by α-alkylation of GVL.
Scheme 88: Ring-opening polymerization of five-membered lactones.
Scheme 89: Synthesis of GVL-based ionic liquids.
Scheme 90: Preparation of butene isomers from GVL under Lewis acid conditions.
Scheme 91: Construction of C5–C12 fuels from GVL over nano-HZSM-5 catalysts.
Scheme 92: Preparation of alkyl valerate from GVL via ring opening/reduction/esterification sequence.
Scheme 93: Construction of 4-acyloxypentanoic acids from GVL.
Scheme 94: Synthesis of 1,4-pentanediol (PDO) from GVL.
Scheme 95: Construction of novel cyclic hemiketal platforms via self-Claisen condensation of GVL.
Scheme 96: Copper-catalyzed lactamization of GVL.
Figure 4: Main scaffolds obtained from HMF.
Scheme 97: Biginelli reactions towards HMF-containing dihydropyrimidinones.
Scheme 98: Hantzsch dihydropyridine synthesis involving HMF.
Scheme 99: The Kabachnik–Fields reaction involving HMF.
Scheme 100: Construction of oxazolidinone from HMF.
Scheme 101: Construction of rhodamine-furan hybrids from HMF.
Scheme 102: A Groebke–Blackburn–Bienaymé reaction involving HMF.
Scheme 103: HMF-containing benzodiazepines by [4 + 2 + 1] cycloadditions.
Scheme 104: Synthesis of fluorinated analogues of α-aryl ketones.
Scheme 105: Synthesis of HMF derived disubstituted γ-butyrolactone.
Scheme 106: Functionalized aromatics from furfural and HMF.
Scheme 107: Diels–Alder adducts from HMF or furfural with N-methylmaleimide.
Scheme 108: Pathway of the one-pot conversion of HMF into phthalic anhydride.
Scheme 109: Photocatalyzed preparation of humins (L-H) from HMF mixed with spoiled HMF residues (LMW-H) and fur...
Scheme 110: Asymmetric dipolar cycloadditions on HMF.
Scheme 111: Dipolar cycloadditions of HMF based nitrones to 3,4- and 3,5-substituted isoxazolidines.
Scheme 112: Production of δ-lactone-fused cyclopenten-2-ones from HMF.
Scheme 113: Aza-Piancatelli access to aza-spirocycles from HMF-derived intermediates.
Scheme 114: Cross-condensation of furfural, acetone and HMF into C13, C14 and C15 products.
Scheme 115: Base-catalyzed aldol condensation/dehydration sequences from HMF.
Scheme 116: Condensation of HMF and active methylene nitrile.
Scheme 117: MBH reactions involving HMF.
Scheme 118: Synthesis of HMF-derived ionic liquids.
Scheme 119: Reductive amination/enzymatic acylation sequence towards HMF-based surfactants.
Scheme 120: The formation of 5-chloromethylfurfural (CMF).
Scheme 121: Conversion of CMF to HMF, levulinic acid, and alkyl levulinates.
Scheme 122: Conversion of CMF to CMFCC and FDCC.
Scheme 123: Conversion of CMF to BHMF.
Scheme 124: Conversion of CMF to DMF.
Scheme 125: CMF chlorine atom substitutions toward HMF ethers and esters.
Scheme 126: Introduction of carbon nucleophiles in CMF.
Scheme 127: NHC-catalyzed remote enantioselective Mannich-type reactions of CMF.
Scheme 128: Conversion of CMF to promising biomass-derived dyes.
Scheme 129: Radical transformation of CMF with styrenes.
Scheme 130: Synthesis of natural herbicide δ-aminolevulinic acid from CMF.
Scheme 131: Four step synthesis of the drug ranitidine from CMF.
Scheme 132: Pd/CO2 cooperative catalysis for the production of HHD and HXD.
Scheme 133: Different ruthenium (Ru) catalysts for the ring-opening of 5-HMF to HHD.
Scheme 134: Proposed pathways for preparing HXD from HMF.
Scheme 135: MCP formation and uses.
Scheme 136: Cu(I)-catalyzed highly selective oxidation of HHD to 2,5-dioxohexanal.
Scheme 137: Synthesis of N‑substituted 3‑hydroxypyridinium salts from 2,5-dioxohexanal.
Scheme 138: Ru catalyzed hydrogenations of HHD to 1,2,5-hexanetriol (a) see ref. [396]; b) see ref. [397]).
Scheme 139: Aviation fuel range quadricyclanes produced by HXD.
Scheme 140: Synthesis of HDGK from HXD and glycerol as a chain extender.
Scheme 141: Synthesis of serinol pyrrole from HXD and serinol.
Scheme 142: Synthesis of pyrroles from HXD and nitroarenes.
Scheme 143: Two-step production of PX from cellulose via HXD.
Scheme 144: Preparation of HCPN from HMF via hydrogenation and ring rearrangement.
Scheme 145: Suggested pathways from HMF to HCPN.
Scheme 146: α-Alkylation of HCPN with ethylene gas.
Scheme 147: Synthesis of 3-(hydroxymethyl)cyclopentylamine from HMF via reductive amination of HCPN.
Scheme 148: Production of LGO and Cyrene® from biomass.
Scheme 149: Synthesis of HBO from LGO and other applications.
Scheme 150: Construction of m-Cyrene® homopolymer.
Scheme 151: Conversion of Cyrene® to THFDM and 1,6-hexanediol.
Scheme 152: RAFT co-polymerization of LGO and butadienes.
Scheme 153: Polycondensation of HO-LGOL and diols with dimethyl adipate.
Scheme 154: Self-condensation of Cyrene® and Claisen–Schmidt reactions.
Scheme 155: Synthesis of 5-amino-2-(hydroxymethyl)tetrahydropyran from Cyrene®.
Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform
- Jie Yan,
- Shaodong Sun,
- Minghao Wang and
- Si Wu
Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159
- [35][36][37][38][39][40][41]. Notably, the utilization of azobenzene-based materials in solar thermal storage applications is gaining considerable attention due to their advantages in low synthesis cost, facile molecular design, exceptional cycling stability, and superior fatigue resistance [6][8
- enables each azobenzene unit to store >200% more energy than isolated molecules, while achieving multi-order-of-magnitude improved storage lifetime and resistance to material degradation during repeated cycling. Feng and co-workers covalently grafted azobenzene groups onto RGO templates (Figure 3b) and
Graphical Abstract
Figure 1: Schematic diagram of molecular solar thermal energy storage system.
Figure 2: Photoisomerization of different types of molecular optical switches. Figure 2 was redrawn from [8].
Figure 3: Nanocarbon-based azobenzene polymer solar thermal fuels: (a) SWCNT templating. Figure 3a is from [43] (T. J. Kuc...
Figure 4: Conjugated azobenzene polymer solar thermal fuels: (a) Photoisomerization and thermally induced rev...
Figure 5: Linear azobenzene polymer solar thermal fuels: (a) Schematic illustration of the trans-to-cis isome...
Figure 6: Representative examples of azobenzene small-molecule derivative solar thermal fuels. (a) Polarized ...
Figure 7: (a) Deicing test of charged solar thermal fuels under green light irradiation (550 nm). Figure 7a was reprin...
Photoswitches beyond azobenzene: a beginner’s guide
- Michela Marcon,
- Christoph Haag and
- Burkhard König
Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143
- forward and backward isomerisation can occur simultaneously. Moreover, some unwanted photochemical side reactions ΦS can occur, as shown in the Equation 4: A is one state of the photoswitch, B the second state, and B’ a generic degradation product. Fatigue resistance measures how many times the
- photoswitch can be switched before it is degraded by side reactions. It is typically reported as cyclability Z50, which “is the number of cycles required to reduce the initial absorbance at a specific wavelength by 50%” [3]. The quantum yield ΦS of these side reactions determines the resistance to fatigue of
- the E-chair isomer [51]. All the compounds show excellent resistance to fatigue. The behaviour of some (hetero)diazocines was also studied in water and solvent mixtures [50][51]. Interestingly, N-acetyl-diazocine possesses overall comparable properties and a longer thermal half-life, and it is also
Graphical Abstract
Figure 1: Energy diagram of a two-state photoswitch. Figure 1 was redrawn from [2].
Figure 2: Example of the absorption spectra of the isomers of a photoswitch with most efficient irradiation w...
Scheme 1: Photoswitch classes described in this review.
Figure 3: Azoheteroarenes.
Scheme 2: E–Z Isomerisation (top) and mechanisms of thermal Z–E isomerisation (bottom).
Scheme 3: Rotation mechanism favoured by the electron displacement in push–pull systems. Selected examples of...
Figure 4: A) T-shaped and twisted Z-isomers determine the thermal stability and the Z–E-PSS (selected example...
Figure 5: Effect of di-ortho-substitution on thermal half-life and PSS.
Figure 6: Selected thermal lifetimes of azoindoles in different solvents and concentrations. aConcentration o...
Figure 7: Aryliminopyrazoles: N-pyrazoles (top) and N-phenyl (bottom).
Scheme 4: Synthesis of symmetrical heteroarenes through oxidation (A), reduction (B), and the Bayer–Mills rea...
Scheme 5: Synthesis of diazonium salt (A); different strategies of azo-coupling: with a nucleophilic ring (B)...
Scheme 6: Synthesis of arylazothiazoles 25 (A) and heteroaryltriazoles 28 (B).
Scheme 7: Synthesis of heteroarylimines 31a,b [36-38].
Figure 8: Push–pull non-ionic azo dye developed by Velasco and co-workers [45].
Scheme 8: Azopyridine reported by Herges and co-workers [46].
Scheme 9: Photoinduced phase transitioning azobispyrazoles [47].
Figure 9: Diazocines.
Scheme 10: Isomers, conformers and enantiomers of diazocine.
Scheme 11: Partial overlap of the ππ* band with electron-donating substituents and effect on the PSS. Scheme 11 was ada...
Figure 10: Main properties of diazocines with different bridges. aMeasured in n-hexane [56]. bMeasured in THF. cMe...
Scheme 12: Synthesis of symmetric diazocines.
Scheme 13: Synthesis of asymmetric diazocines.
Scheme 14: Synthesis of O- and S-heterodiazocines.
Scheme 15: Synthesis of N-heterodiazocines.
Scheme 16: Puromycin diazocine photoswitch [60].
Figure 11: Indigoids.
Figure 12: The main representatives of the indigoid photoswitch class.
Scheme 17: Deactivation process that prevents Z-isomerisation of indigo.
Figure 13: Stable Z-indigo derivative synthesised by Wyman and Zenhäusern [67].
Figure 14: Selected examples of indigos with aliphatic and aromatic substituents [68]. Dashed box: proposed π–π in...
Scheme 18: Resonance structures of indigo and thioindigo involving the phenyl ring.
Scheme 19: Possible deactivation mechanism for 4,4'-dihydroxythioindigo [76].
Scheme 20: Effect of different heteroaryl rings on the stability and the photophysical properties of hemiindig...
Figure 15: Thermal half-lives of red-shifted hemithioindigos in toluene [79]. aMeasured in toluene-d8.
Scheme 21: Structures of pyrrole [81] and imidazole hemithioindigo [64].
Figure 16: Examples of fully substituted double bond hemithioindigo (left), oxidised hemithioindigos (centre),...
Scheme 22: Structure of iminothioindoxyl 72 (top) and acylated phenyliminoindolinone photoswitch 73 (bottom). ...
Scheme 23: (top) Transition states of iminothioindoxyl 72. The planar transition state is associated with a lo...
Scheme 24: Baeyer–Drewsen synthesis of indigo (top) and N-functionalisation strategies (bottom).
Scheme 25: Synthesis of hemiindigo.
Scheme 26: Synthesis of hemithioindigo and iminothioindoxyl.
Scheme 27: Synthesis of double-bond-substituted hemithioindigos.
Scheme 28: Synthesis of phenyliminoindolinone.
Scheme 29: Hemithioindigo molecular motor [85].
Figure 17: Arylhydrazones.
Scheme 30: Switching of arylhydrazones. Note: The definitions of stator and rotor are arbitrary.
Scheme 31: Photo- and acidochromism of pyridine-based phenylhydrazones.
Scheme 32: A) E–Z thermal inversion of a thermally stable push–pull hydrazone [109]. B) Rotation mechanism favoured...
Scheme 33: Effect of planarisation on the half-life.
Scheme 34: The longest thermally stable hydrazone switches reported so far (left). Modulation of thermal half-...
Figure 18: Dependency of t1/2 on concentration and hypothesised aggregation-induced isomerisation.
Figure 19: Structure–property relationship of acylhydrazones.
Scheme 35: Synthesis of arylhydrazones.
Scheme 36: Synthesis of acylhydrazones.
Scheme 37: Photoswitchable fluorophore by Aprahamian et al. [115].
Scheme 38: The four-state photoswitch synthesised by the Cigáň group [116].
Figure 20: Diarylethenes.
Scheme 39: Isomerisation and oxidation pathway of E-stilbene to phenanthrene.
Scheme 40: Strategies adapted to avoid E–Z isomerisation and oxidation.
Scheme 41: Molecular orbitals and mechanism of electrocyclisation for a 6π system.
Figure 21: Aromatic stabilisation energy correlated with the thermal stability of the diarylethenes [127,129].
Figure 22: Half-lives of diarylethenes with increasing electron-withdrawing groups [128,129].
Scheme 42: Photochemical degradation pathway promoted by electron-donating groups [130].
Figure 23: The diarylethenes studied by Hanazawa et al. [134]. Increased rigidity leads to bathochromic shift.
Scheme 43: The dithienylethene synthesised by Nakatani's group [135].
Scheme 44: Synthesis of perfluoroalkylated diarylethenes.
Scheme 45: Synthesis of 139 and 142 via McMurry coupling.
Scheme 46: Synthesis of symmetrical derivatives 145 via Suzuki–Miyaura coupling.
Scheme 47: Synthesis of acyclic 148, malonic anhydride 149, and maleimide derivatives 154.
Figure 24: Gramicidin S (top left) and two of the modified diarylethene derivatives: first generation (bottom ...
Scheme 48: Pyridoxal 5'-phosphate and its reaction with an amino acid (top). The analogous dithienylethene der...
Figure 25: Fulgides.
Scheme 49: The three isomers of fulgides.
Scheme 50: Thermal and photochemical side products of unsubstituted fulgide [150].
Figure 26: Maximum absorption λc of the closed isomer compared with the nature of the aromatic ring and the su...
Scheme 51: Possible rearrangement of the excited state of 5-dimethylaminoindolylfulgide [153].
Figure 27: Quantum yields of ring closure (ΦE→C) and E–Z isomerisation (ΦE→Z) correlated with the increasing s...
Scheme 52: Active (Eα) and inactive (Eβ) conformers (left) and the bicyclic sterically blocked fulgide 169 (ri...
Scheme 53: Quantum yield of ring-opening (ΦC→E) and E–Z isomerisation (ΦE→Z) for different substitution patter...
Scheme 54: Stobbe condensation pathway for the synthesis of fulgides 179, fulgimides 181 and fulgenates 178.
Scheme 55: Alternative synthesis of fulgides through Pd-catalysed carbonylation.
Scheme 56: Optimised synthesis of fulgimides [166].
Scheme 57: Photoswitchable FRET with a fulgimide photoswitch [167].
Scheme 58: Three-state fulgimide strategy by Slanina's group.
Figure 28: Spiropyrans.
Scheme 59: Photochemical (left) and thermal (right) ring-opening mechanisms for an exemplary spiropyran with a...
Figure 29: Eight possible isomers of the open merocyanine according to the E/Z configurations of the bonds hig...
Scheme 60: pH-Controlled photoisomerisation between the closed spiropyran 191-SP and the open E-merocyanine 19...
Scheme 61: Behaviour of spiropyran in water buffer according to Andréasson and co-workers [180]. 192-SP in an aqueo...
Scheme 62: (left box) Proposed mechanism of basic hydrolysis of MC [184]. (right box) Introduction of electron-dona...
Scheme 63: Photochemical interconversion of naphthopyran 194 (top) and spirooxazine 195 (bottom) photoswitches...
Scheme 64: Synthesis of spiropyrans and spirooxazines 198 and the dicondensation by-product 199.
Scheme 65: Alternative synthesis of spiropyrans and spirooxazines with indolenylium salt 200.
Scheme 66: Synthesis of 4’-substituted spiropyrans 203 by condensation of an acylated methylene indoline 201 w...
Scheme 67: Synthesis of spironaphthopyrans 210 by acid-catalysed condensation of naphthols and diarylpropargyl...
Scheme 68: Photoswitchable surface wettability [194].
Figure 30: Some guiding principles for the choice of the most suitable photoswitch. Note that this guide is ve...
Research progress on calixarene/pillararene-based controlled drug release systems
- Liu-Huan Yi,
- Jian Qin,
- Si-Ran Lu,
- Liu-Pan Yang,
- Li-Li Wang and
- Huan Yao
Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139
- focusing on the tumor microenvironment to develop supramolecular systems that are highly specific and capable of responding to multiple stimuli. These advanced systems aim to target and penetrate tumor cells effectively, mitigate drug resistance caused by tumor cell uptake, and ultimately enhance clinical
Graphical Abstract
Figure 1: Schematic diagram of drug-controlled release mechanisms based on aromatic macrocycles.
Figure 2: Chemical structure of a) calix[n]arene (m = 1,3,5), and b) pillar[n]arene (m = 1,2,3).
Figure 3: Changes in pH conditions cause the release of drugs from CA8 host–guest complexes [101]. Figure 3 was adapted wi...
Figure 4: The illustration of the pH-mediated 1:1 complex formation between the host and guest molecules in a...
Figure 5: Illustration of the pH-responsive self-assembly of mannose-modified CA4 into micelles and the subse...
Figure 6: Illustration of the assembly of supramolecular prodrug nanoparticles from WP6 and DOX-derived prodr...
Figure 7: Illustration of the formation of supramolecular vesicles and their pH-dependent drug release [93]. Figure 7 was...
Figure 8: Schematic illustration of the application of the multifunctional nanoplatform CyCA@POPD in combined...
Figure 9: Illustration of the photolysis of an amphiphilic assembly via CA-induced aggregation [114]. Figure 9 was reprint...
Figure 10: Schematic illustration of drug release controlled by the photo-responsive macroscopic switch based ...
Figure 11: Schematic illustration of the formation process of Azo-SMX and its photoisomerization reaction unde...
Figure 12: Schematic illustration of the enzyme-responsive behavior of supramolecular polymers [95]. Figure 12 was used wit...
Figure 13: Schematic illustration of the amphiphilic assembly of SC4A and its enzyme-responsive applications [119]. ...
Figure 14: Stimuli-responsive nanovalves based on MSNs and choline-SC4A[2]pseudorotaxanes, MSN-C1 with ester-l...
Figure 15: A schematic diagram showing the construction of a supramolecular system by host–guest interaction b...
Figure 16: A schematic diagram showing the formation of the host–guest complex DOX@Biotin-SAC4A by biotin modi...
Figure 17: A schematic diagram showing the self-assembly of CA4 into a hypoxia-responsive peptide hydrogel, wh...
Figure 18: Schematic illustration of the formation process of Lip@GluAC4A and the release of Lip under hypoxic...
Figure 19: Schematic illustration of the construction of a supramolecular vesicle based on the host–guest comp...
Figure 20: Schematic illustration of WP6 self-assembly at pH > 7, and the stimulus-responsive drug release beh...
Figure 21: Schematic illustration of the formation of supramolecular vesicles based on the WP5⊃G super-amphiph...
Figure 22: Schematic illustrations of the host–guest recognition of QAP5⊃SXD, the formation of the nanoparticl...
Figure 23: Schematic illustration of the activation of T-SRNs by acid, alkali, or Zn2+ stimuli to regulate the...
Figure 24: Illustration of the triggered release of BH from CP[5]A@MSNs-Q NPs in response to a drop in pH or a...
Figure 25: Illustration of the supramolecular amphiphiles TPENCn@1 (n = 6 and 12) self-assembling with disulfi...
Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade
- Feng Zhou,
- Chuansong Duanmu,
- Yanxing Li,
- Jin Li,
- Haiqing Xu,
- Pan Wang and
- Kai Zhu
Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132
- stainless steel demonstrates corrosion resistance in individual exposures to concentrated nitric acid or sulfuric acid due to passivation layer formation. However, during nitration using both acids simultaneously, progressive HNO3 consumption and water generation may reduce acid concentrations below
Graphical Abstract
Figure 1: Three key dimensions of a complete nitration process.
Figure 2: A typical continuous-flow nitration reaction system.
Figure 3: Corrosion characteristics of common wetted materials used in continuous-flow nitration system. Note...
Figure 4: Analysis of the literature on continuous-flow nitration reaction over the past decade.
Scheme 1: Model reaction for the homogeneous nitration by nitric acid/mixed acid.
Figure 5: Safety assessment criteria for nitration reactions. Notes: apressure-independent; bno hazards arisi...
Figure 6: Guide for the investigation of continuous-flow nitration processes.
Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds
- Lidia Zaharieva,
- Vera Deneva,
- Fadhil S. Kamounah,
- Nikolay Vassilev,
- Ivan Angelov,
- Michael Pittelkow and
- Liudmil Antonov
Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105
- resistance [1][2][3][4]. In addition to their conventional use, azodyes have unique optical properties, defined by the E/Z isomerization [5][6] and by the tautomeric proton exchange [3][7][8][9][10][11], when a OH or NH group is present on a suitable position in the molecule. Both processes are strongly
Graphical Abstract
Scheme 1: Investigated compounds.
Scheme 2: Long-range PT in the studied compounds along with undesired processes of E/Z isomerization. The ind...
Figure 1: Simulated absorption spectra of the tautomers of 1 in toluene. The spectra in acetonitrile are show...
Figure 2: Normalized absorption spectra of 1.
Figure 3: Absorption spectra of 1 in acetonitrile with stepwise addition of water.
Figure 4: VT 1H NMR spectra of compound 1 in acetonitrile-d3.
Figure 5: Changes in the absorption spectrum of 2 in acetonitrile upon addition of trifluoroacetic acid (TFA)...
Figure 6: Ground (M06-2X/TZVP) and excited (CAM-B3LYP/TZVP) state potential energy surface of compound 1 in t...
Figure 7: Changes of the absorbance of compound 1 at 465 nm in toluene upon turning on and off the irradiatio...
Figure 8: a) Change of ΔE(K-E) in kcal/mol as a function of the substitution on different positions (2–6) in ...
Scheme 3: Perspective switching compounds, generated by the computational quantum chemistry calculations.
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
- Biochemistry, Federal University of Lafia, Nigeria 10.3762/bjoc.21.103 Abstract Pseudomonads strains represent a promising source of bioactive compounds with potential pharmaceutical applications. The necessity to find new drugs is underscored by the increased concern over antimicrobial resistance in the
Graphical Abstract
Figure 1: Structures of the pseudomonins D–G (1–4), pseudomonine (5), pseudomonin B (6) and salicylic acid (7...
Figure 2: Key HMBC, 1H-1H COSY and NOE correlations.
Figure 3: Extracted ion chromatogram and corresponding mass spectrum of compound 4 in the crude extract.
Figure 4: Proposed biosynthetic scheme for the formation of compounds (1–4).
