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

• fluorine gauche effects to evaluate significant conformational biases in all of the possible isomers. Achieving conformational control upon the introduction of a second fluorine atom in fluoropyrrolidine presents challenges. Unlike the chair-like conformation of six-membered rings, five-membered rings lack

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

• and oxidation potentials. Electrochemical methods Synthetic electrochemistry is a powerful tool offering excellent control over reaction kinetics and selectivity [86]. Electrochemical oxidation has been demonstrated as an efficient means for generating benzylic cations, allowing for the introduction

• -oxidation and decomposition to improve the reaction efficiency overall. Conclusion The fluorination of benzylic C(sp3)–H bonds provides rapid access to an important functional group used in medicinal chemistry to control the pharmacokinetic profile of drug candidates. Historical and recent research efforts

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• peroxide catalyzed by tetrabutylammonium iodide (TBAI). By utilizing these readily available bulk chemicals a variety of cyclic β-ketocarbonyl derivatives can be efficiently α-azidated under operationally simple conditions. Control experiments support a mechanistic scenario involving in situ formation of

• -yielding conditions for the synthesis of 2a, we next carried out a series of control experiments in order to address the role of the catalyst’s counter anion and the oxidant (Table 2). Running the reaction of 1a and NaN3 in the presence of stoichiometric amounts of Bu4NI3, I2, Bu4NIO3, or Bu4NIO4 did not

• the presence of a catalytic amount of tetrabutylammonium iodide (TBAI). Control experiments support a mechanistic scenario proceeding via in situ formation of a catalytically competent quaternary ammonium hypoiodite first. This higher oxidation state species then facilitates the α-iodination of the

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• , the corresponding alkylnitrile product was obtained in 86% yield after electrolysis at 3.0 mA for 4 hours, demonstrating the high Faradaic efficiency of the reaction (Table 1, entry 5) [46]. Control experiments revealed that Ce catalyst, Cu catalyst, light, and electricity were all essential for the

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• antibiotic-sparing anti-infective drugs. Building synthetic glycoconjugates for the inhibition and modulation of bacterial lectins have shown promising results. Light-sensitive lectin ligands could allow the modulation of lectins activity with precise spatiotemporal control. Despite the potential of

• /off or from low to high. This strategy can be used for specific targeting or local drug activation to reduce its toxicity [14]. There is an increasing use of the photoisomerization to control the conformation as well as the activities of various biomolecules with the development of photopharmacology

• [11][12][13][14][15][16][17][18]. The group of Lindhorst has reported a series of mannosyl azobenzenes targeting E. coli lectin FimH, demonstrating the possibility to control the type 1 fimbriae-mediated bacterial adhesion to a self-assembled monolayer of mannosyl azobenzene on a gold surface [19][20

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

• elongated growing chain may undergo further processing by KR, DH, and ER domains, generating β-hydroxy, α,β-alkene, and saturated β-methylene groups, respectively (Figure 1a). KR domains have garnered significant attention from researchers due to their ability to control the stereochemistry at the α- and β

Synthesis of cyclic β-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation

• Md Azadur Rahman,
• Hirofumi Endo,
• Takashi Yamamoto,
• Shoma Okushiba,
• Norihiko Sasaki and
• Toshiki Nokami

Beilstein J. Org. Chem. 2024, 20, 1421–1427, doi:10.3762/bjoc.20.124

• ][7][8][9][10]. Thus, chemical glycosylation has to be improved to be able to synthesize complex oligosaccharides, including cyclic oligosaccharides. In this context, electrochemical glycosylation is an important alternative to conventional chemical glycosylations because the precise control of

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• procedures [16], our consolidated 3-CR strategy [17][18][19] implicates a careful selection of the starting components that ensures the installation of functionalities to be converged, by regioselective control, in different ring-closing processes [20][21]. With these considerations in mind and with the aim

• process and developed a catalytic system-controlled selective intramolecular N-annulation process for ring-fused biheterocyclic N,O-aminal derivatives as stable imine equivalents and useful tools for new bond formation in view of further fused-heterocylization processes. Moreover, control experiments

• formation of N,O-aminals 5 and hemiaminals 6. Control mechanistic experiments. Optimization conditions for the Lewis acid-catalyzed intramolecular cyclization of 4a. Supporting Information Supporting Information File 16: General experimental information, synthetic procedures, analytical data and NMR

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• entry 7 in Table 1, resulting in the formation of the desired oxazoline product 3 in 61% isolated yield. Control reactions in the absence of either the precatalyst or oxidant afforded no product formation (Table 1, entries 11 and 12). The control reaction in the absence of the lithium salt only afforded

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• was applicable to various carboxylic acids with electron-donating as well as electron-withdrawing substituents but unfortunately, aliphatic acids were not effective in this reaction. In addition, several control experiments, such as fluorescence quenching and Stern–Volmer studies, were done to analyze

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• the reaction efficiency (Table 1, entries 4–7). The effects of a series of redox mediators on the reaction outcomes were examined, and none gave a better reaction outcome than 1,3-DCB (Table 1, entries 8–12). Control experiments revealed that both visible-light irradiation and the presence of 1,3-DCB

• , providing the corresponding product 3aa in 74% yield. Several control experiments were conducted to gain insight into the reaction mechanism of the electroreductive process. The hydroarylation of cyclopropane-substituted styrene 2l resulted in the formation of ring-opening product 3al’, and the simple

• ), 1,3-DCB (50 mol %), H2O (5.0 mmol), Et4NCl (0.1 mmol), MeCN (3 mL), Al(+)-Pt(−), 7.5 mA/cm2, 4.5 F/mol, 0 °C, blue LEDs. a4.5 F/mol. b2 (5 equiv). cMeCN (3 mL). d5 F/mol. 1,3-DCB, 1,3-dicyanobenzene. Gram-scale reaction and control experiments. Plausible mechanism. Evaluation of reaction conditions.a

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• reactants. We note here, circumstantially, that no Cope rearrangement products of cis-eunicellanes have been reported. Overall, the trans ring fusion of the 2E,6E-trans-eunicellanes appears to control whether Cope rearrangement is energetically possible. In the same biosynthetic study [10], we also

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113

• ; separation; Introduction Single-walled carbon nanotubes (SWNTs) have been attracting considerable interest due to their unique physical and chemical properties. For their further applications, structural control of SWNTs is of great importance, since the electronic and optical properties significantly

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• adducts, with stereochemistry control [4][5]. Unquestionable potential of application in the pharmaceutical industry is recognizable by the number of APIs obtained by this reaction approach [6][7]. The oxindole framework is a privileged unit, recognized massively by its extensive biological applications

• . The half-maximal growth inhibitory concentration (GI50) values after 48 hours of exposure were calculated for each compound (Table S1, Supporting Information File 1). The standard anticancer drug cisplatin (CDDP) was used as positive control. The results are viewed as GI50 range plot (Figure 3). The

Introduction of peripheral nitrogen atoms to cyclo-meta-phenylenes

• Koki Ikemoto and
• Hiroyuki Isobe

Beilstein J. Org. Chem. 2024, 20, 1207–1212, doi:10.3762/bjoc.20.103

• , including pyridinic, pyrrolic and graphitic nitrogen, play important roles in determining the properties and functions (Figure 1a), top-down, physical production does not enable control of the doped structures with atomic precision. The bottom-up chemical syntheses of molecular nanocarbons have thus become

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• , compounds 4 and 5 were detected, and notably, a small amount of 10 was also observed (Figure 1, trace e). As expected, in the negative control reactions, 8 was spontaneously oxidized to 1 without any enzyme added, and no 4, 5, or 10 was observed; 1 remained unchanged in the reaction mixture with Fre, NADH

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• best of our knowledge, this study is unique in the sense that there are no previous reports on the use of bismuth triflate as catalyst for a classic Nazarov reaction. There is also no reported precedent for the preparation of indanones with different substitution patterns through simple control of the

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

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

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

• condensation with ketones, yielding an α,β-unsaturated compound, which was hydrogenated by the manganese hydride species, resulting in the final alkylated product (Scheme 25). A set of deuterium labelling tests and additional control studies determined that the alcohol dehydrogenation was aided by an

• control studies with Hg and TEMPO indicated that the reactions were homogeneous and did not proceed through a radical pathway. Synthesis of heterocycles via C–C and C–N bond formation In 2016, Beller and co-workers reported an intramolecular cyclization using 2-(2-aminophenyl)ethanol for the synthesis of

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

• observed that the β-anomer of charge-neutral nucleoside Vb exhibited similar inhibition of hCDA as the control dZ (IIc). Presence of a negative charge in nucleoside Va led to lack of inhibition at pH 7.4. We assumed that protonation of Va might result in some inhibition of hCDA. However, the pKa of Va was

• instead of the target dC in the preferred DNA motif TCA of A3A and A3B on linear DNA. The previously described A3 inhibitor 5'-TTTTFdZAT was used as a control [54][56][57]. The engineered A3A mimic was used in our initial experiments. This is a well-characterised and active derivative of the CTD of A3B

• measured using the NMR-based assay (Figure 2). The results revealed that both anomers of Va do not inhibit engineered A3A mimic even at elevated concentration in comparison to a control ODN containing FdZ (IId) at pH 6.0. It is very likely that a negative charge in nucleobase Va prevents binding to the

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

• halogenation. Of the two alternatives, the latter is more advantageous, due to three favourable features [65][66]: (i) Optimal control as each ring halogenation inhibits further ring halogenations, (ii) ring halogenation do not negatively affect benzylic bromination, and (iii) aryl bromides often display

Novel route to enhance the thermo-optical performance of bicyclic diene photoswitches for solar thermal batteries

• Akanksha Ashok Sangolkar,
• Rama Krishna Kadiyam and
• Ravinder Pawar

Beilstein J. Org. Chem. 2024, 20, 1053–1068, doi:10.3762/bjoc.20.93

• propensity of the Id and IId couples towards the undesired thermal degradation product. This clearly indicates that the unit used for elongation of the unsaturated bridge is crucial to control the reversibility of the photoswitching cycle or the stability of the photoproduct against undesired thermal

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• building blocks 1,2-aceanthrylenedione and 12, as detailed in Table S1 (Supporting Information File 1). However, an inseparable unknown impurity was observed along with the desired product 3a in all cases when analyzed by 1H NMR. Under strict temperature and time control (80 °C for 72 hours) using 2.5

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• ) Graphical representation of the inhibitory activity of selected compounds evaluated from the gels obtained in the primer extension assay. The percentage of inhibition (against control) was plotted against the logarithm of the concentration of compounds. The results were fitted to sigmoidal dose–response

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• . coelicolor W75, a strain known to produce the MMF molecules was examined, and S. coelicolor M145, a control that does not contain the biosynthetic machinery necessary to produce MMFs but is otherwise genetically identical to S. coelicolor W75. Controls containing just the cell supernatant, as well as

• reactions of the cell supernatant with the maleimide probe, were run on the UPLC-MS after reacting for 18 h. As expected, samples from S. coelicolor M145 did not show any MMFs present in either the control sample or the probe-treated sample, even after concentrating the sample 25-fold. Compound 5 and its

• present. C. Representative UV trace of the reaction products; probe 6, MMF5 (5), and MMF5 cycloadduct 24. All reactions were performed a minimum of three times with similar results being observed in all three replicates. A. The UV trace (254 nm) for M145 control, M145 + probe 6, W75 control, and W75

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• elimination of methanol favored by the evaporation process. The instability of hemiaminal ethers was previously described in literature [19] during work-up. We then found that careful control of the drying conditions, thus avoiding complete drying of the crude mixture prevents degradation of the Heck products