Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• osmolarity using ten different technical additives including organic solvents, polymers, and salts. It is shown that the synthesis of two model proteins, namely superfolder GFP (sfGFP) and the enzyme truncated human cyclic GMP-AMP synthase fused to sfGFP (thscGAS-sfGFP), is very robust against most of the

• properties beyond physiological ranges. We also tested several organic solvents that are miscible and non-miscible with water. For the experiments, two model proteins, the superfolder GFP (sfGFP) and the enzyme human cyclic GMP-AMP synthase-sfGFP, were used, which differ in their size (sfGFP: 27 kDa, thscGAS

• the production of non-ribosomal peptide synthetases with a molecular weight higher than 100 kDa [57]. However, these enzymes are often of great interest for specific applications in biomanufacturing. Cyclic GMP-AMP synthase (cGAS) is one of these enzymes. cGAS and its biocatalytic product 2’3’-cyclic

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• ][62][63][64], we conducted research on their organic reactions in water and reported some good results, such as thioacetalization using ketene dithioacetals as odorless thiol equivalent [65], Friedel–Crafts alkylation of cyclic ketene dithioacetals with alcohols [66], the hydrolysis of chain α-oxo

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• intramolecular addition of enamine I to the C3=O to form intermediate II, which dehydrates to cyclic carbinol III. Finally, dehydration of intermediate III yields anilines 3. Conclusion In summary, a method for the synthesis of substituted meta-hetarylanilines under mild conditions starting from 1,3-diketones

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• original Biginelli reaction shown in Scheme 1A was significantly extended by variation of the 1,3-dicarbonyl-containing building blocks. Many groups have elegantly demonstrated the synthetic versatility of numerous enolizable carbonyl components, including β-keto esters, cyclic/acyclic β-diketones, β-keto

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• (93% ee) to the homogeneous catalyst (94% ee) in the alcoholytic desymmetrisation of a cyclic anhydride 34 albeit requiring a slightly longer reaction time. Compared to polymer films, textile fibres offer a significantly higher surface area, potentially contributing to the maintenance of high

• asymmetric Michael addition of pentane-2,4-dione (32) and trans-β-nitrostyrene (11). Alcoholytic desymmetrisation of a cyclic anhydride 34 catalysed by polyamide-supported cinchona sulfonamide 36. Funding This research was funded by the National Research, Development, and Innovation Office (grant number

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• Lewis acid–base complexes (t-BuNC→BH3) to generate the corresponding isocyanide–boryl radicals 17 (t-BuNC→BH2•), which can be observed by ESR (Scheme 10b) [47]. However, the synthetic application of this boryl radical has not been investigated. Among the cyclic diboron compounds, a series of five

• -membered cyclic diboron compounds 18 undergo an insertion reaction of isocyanides into the boron–boron single bond of 18 under mild conditions without the addition of any additives (Scheme 11a) [48]. The reaction is thought to proceed by an ionic mechanism. Recently, several insertion-type reactions of

• radical, which induces 5-exo cyclization. The following hydrogen abstraction, intramolecular ionic cyclization, and hydrolysis during chromatography on silica gel affords the cyclic amide in good yield. They further applied this radical cyclization reaction as a key step in the synthesis of (±)-α-kainic

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• -oxodithioesters 48 react with primary or cyclic aliphatic amines, resulting in the formation of β-oxothioamides 50, which can then be directly converted into the corresponding 5-aminopyrazoles 49 with aromatic hydrazines in the presence of catalytic amounts of acetic acid (Scheme 14) [68]. The process exhibits

• regioselectivity, with 3,4-fused pyrazoles being accessible when cyclic β-oxodithioesters are employed as substrates. However, aromatic amines cannot be successfully employed in the sequence. Alkenoyl derivatives as key intermediates The Michael addition and cyclocondensation of hydrazines and α,β-unsaturated

• generated hydrazones were cyclized with simple ketones to pyrazolines. The oxidation to the corresponding 4-halo-substituted pyrazoles 69 can be achieved in a one-pot fashion by halogenation with iodine chloride or elemental bromine (Scheme 24) [102]. When cyclic ketones are used, fused products 70 are

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• formation of dimeric side products. Cyclic voltammetry analysis suggested an initial anodic single electron transfer (SET) to radical cation 5, cyclization and deprotonation. Subsequent SET oxidation in solution by 5 led to cation 7. Final deprotonation furnished aromatic cycle 4. In 2022, Zhang et al

• hydrazones initiated with the SET anodic oxidation of the hydrazone and deprotonation to form the N-centered radical 10. After aza-cyclization on the aromatic ring, a second SET oxidation and deprotonation delivered the heterocycle 9. This mechanism was supported by cyclic voltammetry analysis of a model

• electromediated by iodine would furnish aldehyde 56. Electrogenerated iodine would further assist the reaction with ammonia to form N-iodo aldimine intermediate 57. Subsequent radical cycloaddition between 56 and 57 would furnish cyclic hydrazinyl radical 58. Finally, the triazole would be obtained after hydrogen

Radical reactivity of antiaromatic Ni(II) norcorroles with azo radical initiators

• Siham Asyiqin Shafie,
• Ryo Nozawa,
• Hideaki Takano and
• Hiroshi Shinokubo

Beilstein J. Org. Chem. 2024, 20, 1967–1972, doi:10.3762/bjoc.20.172

• CH2Cl2 were examined using cyclic voltammetry (Figure 4). Macrocycle 2a exhibited one reversible oxidation wave at 0.44 V and two reversible reduction waves at −0.85 V and −1.14 V. The electrochemical HOMO–LUMO gap of 2a is 1.29 V, which is larger than that of 1a (1.08 V) [2]. DFT calculations We next

• CH2Cl2. Cyclic voltammogram of 2a in CH2Cl2. Supporting electrolyte: 0.1 M Bu4NPF6; working electrode: glassy carbon; counter electrode: Pt; reference electrode: Ag/AgNO3; scan rate: 50 mV⋅s−1. Reaction of norcorrole 1 with AIBN. Reaction of norcorrole 1 with V-40. Plausible reaction mechanism

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• the treatment of paroxysmal nocturnal hemoglobinuria, and CPI-637 (2), an inhibitor of both cyclic-AMP response element binding protein (CBP) and adenoviral E1A binding protein [14][15][16]. The N2-substituted indazole analogs pazopanib (3), an FDA-approved tyrosine kinase inhibitor used for the

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• the substrate, and thus preventing the possible interaction between the amide moiety and PISA, as opposed to CH3CN. The olefin moiety of the complex then interacts with the exposed central iodine(III) atom in PISA [25], forming the intermediate D. Similar cyclic iodonium intermediates were also

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• compatible to give the respective five-membered pyrrolidines, except for that possessing a 2-nitro group 7. As discussed later with cyclic voltammetric studies, the electron density in the aryl rings does not seem to have a significant impact on the reaction. While benzyl sulfonamide 8 was productive under

• tetrasubstituted alkene 14. Cyclic voltammetric studies have provided further mechanistic insights into electrochemical aza-Wacker cyclizations. As reported by Yoon, a trisubstituted alkene is oxidized at significantly lower potential than aryl sulfonamides, suggesting that the reactions were initiated by single

• -electron oxidation of the alkenes. Although a drop in oxidation potential for the alkene was observed when tethered to an aryl sulfonamide, as detailed by Moeller, rapid intramolecular cyclization would be the key [26][27][28]. We also measured cyclic voltammograms for aryl sulfonamides with and without

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• Bienaymé. On the other hand, the GBB reaction, compared with the Ugi and Passerini reactions, has an undeniable advantage, namely, the possibility of obtaining cyclic, aromatic, and drug-like compounds, rather than linear structures. The immediate consequence of this fact is that there are numerous studies

• -bromoethyl)benzaldehyde 79 was utilized to form the highly reactive cyclic iminium intermediates 81 through the condensation with amidines 80. The subsequent formal [4 + 1] cycloaddition with the isocyanide and the 1,3-H-shift occurred to afford pentacycles 82. Performing the one-pot reaction under the

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• ]quinoline-2,4(1H,3H)-dione cyclic system. The absorption spectra of the methoxy derivatives 2f, 2j and 2n in DMF provide interesting information on the effect of the position of the methoxy group in the core of deazaalloxazine on the absorption maxima (Figure 2). The 8-methoxydeazaalloxazine 2n exhibited a

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• nature on the molecular properties of PASs. Our goal is to delineate specific structure–property relationships that may shed light on these prevalent, yet still mysterious, compounds and serve as design principles for future PASs. Data The molecules in COMPAS-2 contain 11 cyclic building blocks varying

• demonstrates that increasing the diversity of conjugated cyclic building blocks does not have a notable impact on the relative distribution of molecular shapes. In contrast to their relatively high geometric similarity, the molecular properties of the two datasets vary substantially. We compared the

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

• resulting peptides exhibit unique structural features due to thioether bridges between dehydrated serine or threonine (Dha/Dhb) and cysteine (Cys). These thioether bridges lead to cyclic peptides with the modified amino acid lanthionine (Dha-Cys) or methyllanthionine (Dhb-Cys). The strong antimicrobial

• times dehydrated was identified. Cyclization reactions introduced thioether cross-links between dehydrated Thr/Ser residues and specific cysteine thiol groups. However, due to identical masses of dehydrated linear peptides (lacking thioether rings) and cyclic forms (containing Dhb and Dha rings), a

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• cyclic imides. The solid-state structures of the N-phenyl derivatives, determined by X-ray crystallography, reveal changes in packing preference based on the number of aromatic rings in the core. The optical and electronic properties of the title compounds compare favorably with other previously

• robust polymers, supramolecular assemblies, and (opto)electronic materials. The vast majority of this research has focused on 1,2,4,5-benzene (pyromellitic), 1,4,5,8-naphthalene, and 3,4,9,10-perylene diimides. Beyond these, researchers have demonstrated that translocating the cyclic imides around the

• been achieved as well. Other efforts have demonstrated that anthracene diimides (ADIs) can be tuned to achieve decent electron mobilities in electronic settings [13][14]. Although there have been calculations conducted that suggest 6-membered cyclic imides are more compelling than 5-membered cyclic

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

• . The specific quinones formed were guided by the position of an initial hydroxy group on the polycyclic aromatic hydrocarbon. An available para-position in the PAPs gave p-quinones, while hydroxy groups in the 2- or 3-position led to o-quinones. The substrates were analysed by cyclic voltammetry for

• estitmation of the HOMO/LUMO energies to shed more light on this transformation. The easy separation of the supporting electrolyte from the product will allow recycling and makes this a green transformation. Keywords: acetal formation; cyclic voltammetry; flow electrochemistry; green oxidation; polycyclic

• aromatic hydrocarbons; Introduction Quinones and their derivatives are applied in various fields such as chemical, environmental, and pharmaceutical industries [1][2][3][4]. Their cyclic diketone structures can easily transform into intramolecular unsaturated structures, and their distinct physical

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• reactions. To increase the molecular diversity at the morpholine ring, tertiary amines were formed by nucleophilic substitution. A final removal of the cyclic ketal group in aq sulfuric acid provided spiromorpholinone derivatives 134a–e, 136a–e, and 138 (Scheme 37). Spiromorpholinones were evaluated as

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• oxidation of the alcohol. Only small amounts of benzoic acid 4a’ were observed in all reactions with additional AlCl3, suggesting that the additive inhibits the previously observed overoxidation. Surprisingly AlCl3 activated the cyclic tetrazole iodane 1a but had almost no influence on the reactivity of the

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• producing divamide A. Divamide A contains a trimethylated glutamate at the N-terminus (Figure 4), which is installed by DivMT as the final step in divamide A biosynthesis. The presence of the cyclic lysinoalanine moiety is required for this post-translational modification. The addition of other N-terminal

• Epichloë. Epichloëcyclins A–E are cyclic heptameric peptides, all produced from the same precursor GigA. They carry a dimethylated lysine residue; this modification is installed as a final step in the biosynthesis by GigC. Genome mining showed that analogues of the GigA precursor are widespread in fungal

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• conformational stability of proline-rich proteins such as collagen [2]. Therefore, pyrrolidine derivatives are particularly susceptible to conformational control induced by a fluorine substituent. The 5-membered pyrrolidine ring is a cyclic alkylamine that adopts a conformation that resembles the familiar

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• semihydrogenation of alkynes to form Z-alkenes using a PEM reactor [31]. The Pd/C catalyst was essential for the reaction. They recently found that a PEM reactor with a Rh/C catalyst was effective for the stereoselective reduction of cyclic ketones [40]. Nagaki et al. reported the electrochemical deuteration of

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• ; transcriptome mining; Introduction Plants are prolific producers of cyclic peptide natural products, making 1000s of different molecules [1]. While the orbitide [2] and cyclotide [3] classes of peptides are well known, it has been recently discovered that a new class of molecules called burpitides are also

• chair) produced more than 20. Analysis of the predicted core sequence seemed to suggest moroidin-like molecules (Figure 3), but no cyclic peptides have been isolated from any member of this family. Unfortunately, sourcing members of this small family proved challenging and we were unable to evaluate

• burpitide natural products from plants. Phylogenetic visualization of the potential precursor peptides validated families known to make these cyclic peptides, but also suggested new producers. Finally, metabolomic analyses supported the predicted new sources of burpitides, aiding in our understanding of the

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

• ·2HF proved to be the best of the HF·amine reagents screened. The reaction was conducted under constant potential conditions, using cyclic voltammetry prior to electrolysis to determine the appropriate oxidation potential required for each substrate. Under these conditions, yields of up to 65% were