Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• reagents (“cofactors”), they could perform non-biotic reactions, and even have potential for the design of novel active sites that could be transposed into new designer enzymes for optimization [388][389][390][391], since directed evolution requires initial activity to work from. Flexibility vs rigidity

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• growing concerns around environmental sustainability, there is increasing interest in developing photocatalysts that are more accessible, tunable, and eco-friendly. Each section of this document discusses a specific approach to red-light photocatalysis, reflecting the field’s evolution and exploring

• efficient catalytic processes. In the same way, recent advances in red-light photoredox catalysis have expanded the utility of first-row transition metals in a domain traditionally dominated by second- and third-row elements. A prime example of this evolution is the development of a dual photoredox strategy

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• Supporting Information File 1). Upon second oxidation, the former Raman vibrational band upshifts by 24 cm−1 for 12+, and the naphthalene ν(CC)NAP stretching one disappears. Overall, the evolution of the CBD breathing mode, throughout the series 1→1•+→12+ is 1700 → 1689 → 1713 cm−1. Figure 5 shows the Raman

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• stations for consumables and sample storage. Remarkably, through a tedious ten-dimensional parameter search spanning eight days, the robot achieved an impressive hydrogen evolution rate of approximately 21.05 µmol⋅h−1. Despite the initial investment and two-year development timeline, the versatility of

• chromatographic spectra and to automatically assign the peaks to reagents or products depending on the decrease or increase in peak intensity over time. In addition to monitoring the evolution of the reaction, the IR spectral data was processed in real time. This was to ensure the complete consumption of acid

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

• ]. In relation to epilepsy, the etiology of seizures depends on age. In children, seizures are frequently originated by genetic factors, malformations of cortical evolution, and injuries from perinatal events. In adults lacking an inherited tendency, typical causes include encephalitis or meningitis

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• batteries, due to the ease of their structural modification, rich redox chemistry, and robust coordination M–N4 environment [100][101][102][103][104][105]. The key processes employed in energy transfer and storage are the oxygen reduction reaction (ORR), hydrogen evolution reaction (HER), and oxygen

• evolution reaction (OER). There are several reviews focusing on the relationship between metallo-catalyst structures and HER, OER, and ORR performance/mechanisms, selection of the central metal ion, and peripheral functionalization of the catalysts [106][107][108][109]. This review summarizes recent

• , was used for controlling the electrocatalyzed H2 evolution in acidic conditions in acetonitrile [112]. There are not many reported examples of metal-free porphyrin macrocycles as HER electrocatalysts. Metal-free porphyrin macrocycles are capable of multielectron redox processes and have basic amine

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• electrocatalytic hydrogen evolution reactions, a proton source is needed [11]. In this context, trifluoroacetic acid is very frequently chosen as the proton source, because it is a strong acid but just not strong enough to destroy (demetallate) the Ni porphyrin [10]. Covalent attachment of acids facilitates proton

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• . However, it should be noted that anodic oxidations often require electrodes with high resistance to oxidation, such as platinum electrodes, or inert electrodes with a highly developed surface, like reticulated vitreous carbon (RVC). Anodic oxidations generally involve the evolution of hydrogen (indicated

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• transfer reagents; (iv) direct metal-free imine carbanion addition to electrophilic alkene. Class (i) underwent an evolution from catalysis by covalent interaction to chiral hydrogen-bonded catalysis, which allowed the expansion of the allyl component scope from simple allyl to substituted allyl groups

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• this chapter, we first discuss the evolution of physical-organic descriptors for the representation of organocatalysts [82]. Later, we examine the effects of increasing data availability towards the application of ML in this field. 2.1 Evolution of physical-organic descriptors in organocatalysis

• also the structure for which the descriptors are considered. This can either be ensured by expert-knowledge of preselecting relevant structures, for example based on a known mechanism, or by considering information from the entire conformer ensemble. Parallel to the evolution in modelling steric

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

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

• crucial research area in discovering novel antimicrobial compounds [6][7]. Due to its unique position between basic and applied research, it has become an essential tool for identifying compounds with potential therapeutic applications. Genetic and genomic data mining enables the study of the evolution of

• genes and genomes across diverse species and populations. This provides insights into the origins and evolution of genes that have evolved as "tools" in the ongoing biological battles in the microbial world. The biodiversity of specialized metabolites is strain-specific, meaning that even closely

• lanthipeptides produced by these biosynthetic pathways has led to the discovery of many new compounds with potential therapeutic applications during recent years, along with a deeper understanding of their evolution, ecological importance, and gene composition [23]. Lanthipeptides produced by class I and II

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• cations B and C which have only one Clar sextet with two alternative positions. Conclusion The electrochemical oxidation of polycyclic aromatic phenols to quinones represents a green alternative to chemical oxidants. Hydrogen gas evolution can be handled by recycling of the reaction mixture through the

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

• through directed evolution [11]. P450 catalysis during the oxidation phase enabled the total synthesis of mitrephorone A [12], chevalone A [13], polysin [14], excolide B [15], and gedunin [16]. Fe(II)/2OG-dependent dioxygenases, such as FtmOx1, were employed as versatile catalysts in the synthesis of 13

• tricyclic scaffold was produced through scalable chemical synthesis. Subsequently, in vitro enzymatic oxidative functionalizations were carried out during the oxidation stage. The exploration of Bsc9 homologs and directed evolution expanded the scope of substrates of the dioxygenase beyond the natural

• evolution using site-saturation mutagenesis targeting the putative active sites L110 and Y112, led to the variant MoBsc9 Y112M, which substantially improved the enzymatic conversion into 22, achieving an isolated yield of up to 67%. Diastereoselective reduction of the C8 ketone was then achieved using the

A fiber-optic spectroscopic setup for isomerization quantum yield determination

• Anouk Volker,
• Jorn D. Steen and
• Stefano Crespi

Beilstein J. Org. Chem. 2024, 20, 1684–1692, doi:10.3762/bjoc.20.150

• scaled subtraction [14]. Another powerful method to obtain the spectrum of the second isomer is global and target analysis, where time-resolved spectra can be analyzed to find the number of spectral components and the evolution of their concentration over time [36][37]. Additional information, such as a

• molecular switch by UV–vis absorption spectroscopy in operando. We provide all the information necessary to build the setup as well as the scripts and examples to retrieve the quantum yields of forward and backward isomerization of a molecular photoswitch following the evolution of the absorption in the low

• baseline subtraction. UV–vis absorption spectra of azobenzene upon irradiation at 340 nm (methanol solution, 20 °C). a) Evolution of spectra over time under irradiation and b) absorption at 340 nm over time, with fitted total absorbance curve obtained from Equation 5. The curve was obtained from entry 5 of

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• their function is three-fold; as a fluoride source, as a supporting electrolyte and as a proton source, allowing for the hydrogen-evolution reaction as the counter electrode process [91]. Benzylic fluorination with these reagents has been observed as a side-product in the electrochemical generation of

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• their KS domains [27], suggesting that they have diverged at an early point during evolution. Furthermore, both KRS and KRC trees showed that KRs belonging to γ- and δ-modules formed a separate clade distinct from those in β-modules, indicating that the existence of DH domain significantly influences

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• , biochemical and structural studies support a model in which this A3-mediated mutagenesis promotes tumour evolution and strongly influences disease trajectories, including the development of drug resistance and metastasis [18][19][20][21][22][23]. Of the seven A3 enzymes, three (A3A, A3B and A3H) are at least

• A3A and A3B offers a potent strategy to suppress cancer evolution and prolong efficacy of existing anticancer therapies [19][38][39]. Despite of the low sequence identity, CDA and A3 share a similar overall structural topology and a close structural homology for the Zn2+-containing active site. Since

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• negligible adsorption of Br2 at wavelengths shorter than 380 nm [52]. We finally evaluated a variation in the H2O2/HBr molar ratio to determine the optimal amount of H2O2, typically used in a twofold molar ratio relative to HBr [49]. These experiments raised on the observation of gas evolution (presumably O2

Spin and charge interactions between nanographene host and ferrocene

• Akira Suzuki,
• Yuya Miyake,
• Ryoga Shibata and
• Kazuyuki Takai

Beilstein J. Org. Chem. 2024, 20, 1011–1019, doi:10.3762/bjoc.20.89

• Evolution instruments (Horiba) with an excitation laser operated at 532 nm in the wavenumber range from 1000 to 2000 cm−1. FTIR spectra were obtained using an FT/IR-6600 (JASCO) in ATR method with a diamond prism. Magnetic susceptibility measurements were carried out by a superconducting quantum

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• be generated in situ through the reaction of "reactive" chlorides with a proton donor. For instance, the reaction of acetyl chloride with ethanol is exothermic, accompanied by vigorous HCl gas evolution. It is crucial to emphasize that HCl solutions in MeOH, produced from AcCl and MeOH, pose

• hydrochlorination of 1-octene (63) required a combination of alumina and oxalyl chloride (Table 5, entry 3). It should be noted that this reaction needs to be carried out under a well-ventilated hood due to the evolution of toxic carbon monoxide. Kropp and co-workers observed that the remaining 2% of the alkene was

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• duplication events during genome evolution [96]. When expressed in the callus of Nicotiana tabacum, GjCCD4a exhibited a higher efficiency in carotenoid cleavage than CsCCD4a [85]. ALDHs: ALDH utilizes NAD+ or NADP+ as cofactor to catalyze the oxidation of acetaldehyde into carboxylic acids. In 2018, Demurtas

• activity. Screening of novel enzymes for crocin biosynthesis and the directed evolution of known enzymes should facilitate the high-titer production of the key intermediates 5–7 etc. and the efficient conversion of these precursors into crocetin (1) and crocins. In conclusion, crocins are high-value plant

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• AsCPS synthesized copalyl diphosphate and that AsPS then converted it to (−)-sandaracopimaradiene. Since AsPS and AsCPS have distinct domain organizations from those of known fungal TCs and are likely generated through fusion or loss of catalytic domains, our findings provide insight into the evolution

• organizations were discovered, these enzymes would be useful to discuss and further analyze the evolution of TCs in fungi. LRDs in fungi. A) Chemical structures of representative fungal LRDs. B) Reactions catalyzed by selected fungal bifunctional TCs. Sequence analysis of AsPS and AsCPS. A) Biosynthetic gene

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• 31 into 37 and 38 (Figure 7B). These results exemplify the production of oxidized terpenoids and meroterpenoids through the use of non-natural substrates and the application of structure-based mutagenesis. Evolution of αKG-dependent dioxygenase with saturated mutagenesis As meroterpenoids readily

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

• Schrader [3][4], and more flexible variants by Rebek [5][6], Zimmerman [7][8], Bosnich [9] and others [10][11][12]. Initially serving as agents for guest binding and recognition, molecular tweezers have undergone a remarkable evolution, diversifying their applications into the realms of biology, catalysis