Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• (pKaH = 13.6) [2]. Moreover, due to the stability of the monocation they display significantly lower second dissociation constants (pKa2H ≈ 3.0). X-ray crystallographic studies and modelling studies have shown that the first protonation occurs mainly on the N4 nitrogen atom, weakening substantially the

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• , glycosyl fluorides possess a considerably higher thermal and chemical stability compared to the corresponding chlorides (BDE 432 kJ/mol) and bromides (BDE 366 kJ/mol). Due to the advantageous stability during purification, handling and storage, glycosyl fluorides have become widely used glycosyl donors in

• [27]) and coupling partners [28], great attention has been paid to a stereoselective glycosylation by sterically fixed glycosyl fluorides as glycosyl donors [29][30][31]. The enhanced stability of glycosyl fluorides has also allowed to develop a straightforward protecting-group-free strategy towards

• on the stability of halosulfites HalSO2− (Hal = F, Cl, Br or I) that can be formed between halide ions and the SO2 molecule. They disclosed that the formation of fluorosulfite anion (FSO2−) has the highest energy gain and it appears to be stable even in highly polar solvents (ε ≤ 45), while all other

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• -unsaturated acetals 164 in the presence of electron-rich olefins using Ce(NO3)3 and SDS in water [74]. The mechanism of the reaction is shown in Scheme 39, which plausibly proceeded through trapping of oxocarbenium ion 166 in a chair-like transition state. The stability of the acetal under these reaction

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• techniques, such as crystallography, have provided insights to rationalize numerous properties including binding affinity, nuclease stability, and trends observed in the gene silencing. In this review, we discuss the chemistry, biophysical, and structural properties of a number of chemically modified

• , replication, splicing and other fundamental processes in biological information transfer. More specifically, they can affect chemical and thermodynamic stability, folding, secondary and tertiary structure, activity and interactions between nucleic acids, proteins and receptors. Particularly, as far as

• improving metabolic stability, pairing properties (RNA affinity), protein binding and transport/cellular uptake are concerned, chemical modifications are a prerequisite for the discovery and development of oligonucleotide therapeutics [11][12][13][14][15]. Thus, the natural PS and 2'-OMe backbone

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• highly oxidizing and alkaline conditions in the synthesis of 1. We decided to probe the stability of this moiety to acidic conditions. Compound 11 proved to have considerable stability to acidic hydrolysis, suffering only 33% hydrolysis upon stirring in 2 M HCl/MeOH/1,2-dichloroethane 1:4:1 at 35 °C for

• 5 h, with 85% hydrolysis observed after 20 hours. The relative stability of 11 to acidic hydrolysis and its presumably enhanced lipophilicity with respect to a des-fluoro acetal, might presage a role for compounds possessing the acyclic bis(aryloxy)fluoromethane moiety in medicinal or agrochemical

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• of dimedone (2d). Unlike cyclic 1,3-dicarbonyls, the acyclic 1,3-dicarbonyls possess intramolecular hydrogen bonding and are in rapid equilibrium with their keto-form. In polar solvents, the stability of the enol form is further decreased and, therefore, the keto-enol equilibrium lies more towards

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• + modifications led to the formation of duplexes with a thermal stability that was less dependent on the ionic strength than native DNA duplexes. The thermodynamic analysis of the melting curves revealed that it is the reduction in unfavourable entropy, despite the decrease in favourable enthalpy, which is

• . For example, both PNA and modified PNAs have excellent chemical stability, are resistant to enzymatic degradation, and have high binding affinity towards complementary DNA and RNA, but have a tendency to aggregate, require high salt conditions, and have low solubility in water [1][25][26]. LNA (BNA

• ) have an enhanced thermal stability in DNA triplexes and duplexes, a high binding affinity to RNA, and are nuclease resistant [22][26][27][28]. These properties have led to LNA (BNA) being used in various therapeutic ONs that have reached clinical trials [29]. However, the multistep synthesis of LNA and

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• cyclization reactions based on the persistent radical effect. Heating them to 150 °C in tert-butanol provided diverse 1,3,4-trisubstituted pyrrolidones (Table 3). For stability reasons the initially obtained silyl-protected lactams 10a–k were deprotected without isolation by TBAF in THF affording hydroxy

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• the synthesis of fulleropyrazolines is available, their decomposition has been studied insufficiently. The factors determining the relative stability of monoadducts obtained in reactions of C60 with diazo compounds also remain an open issue. Some of the studies by Wudl and co-workers [108] deal with

Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

• Naohiro Horie,
• Takao Yamaguchi,
• Shinji Kumagai and
• Satoshi Obika

Beilstein J. Org. Chem. 2021, 17, 622–629, doi:10.3762/bjoc.17.54

• the stability against nucleases, binding affinity to the targets, and efficacy. We previously reported that oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing the thymine (T) nucleobase show excellent biophysical properties for applications in antisense

• . For applications in antisense technology, chemical modifications aimed at enhancing the duplex-forming ability toward a target RNA (i.e., a complementary single-stranded RNA) and improving the stability against enzymatic degradations are commonly utilized. For instance, antisense oligonucleotides

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• catalysts in the form of ionic liquids (ILs) [209]. Advantages of metallated ILs include low flammability, high thermal stability and versatility. However, their “greenness” and toxicity are still debated [225][226]. Thus, amim[ZnCl3] (amin = 1-allyl-3-methylimidazolium, Table 4, entry 1) [227] and amim

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• provokes delipidation of the interfacial film. The incorporation of the F-lipopeptides 1–3 in microbubbles with a shell of DPPC and dipalmitoylphosphatidylethanolamine-PEG2000 decreased their mean diameter and increased their stability, the best results being obtained for the C8F17-bearing lipopeptide 3

• . By contrast, the hydrocarbon lipopeptide led to microbubbles with a larger mean diameter and a significantly lower stability. Keywords: adsorption at fluid interfaces; drug delivery; microbubble targeting; molecular imaging; monolayer; perfluoroalkylated lipopeptide; solid-phase peptide synthesis

• lipopeptides specifically designed for the incorporation in the phospholipid shell of medical microbubbles (MBs) (Scheme 1a). DPPC is widely used in the formulation of MBs, often in combination with a PEGylated dipalmitoylphosphatidylethanolamine (DPPE-PEG2000) that further enhances MB stability [31][32][33

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• structural, catalytic, energetic, and transport. The introduction of organofluorine components into proteins is typically expected to alter their structure, stability and/or specific features associated with their functional roles [8][9][10][11]. The replacement of natural amino acid residues with the ones

• properties. These factors may translate into an altered structure and stability of a protein containing a fluorinated fragment. What consequences fluorination would have regarding the fitness and survival of the organism relying on fluorine-containing proteins remains an open question. In this context, the

• incorporates them into proteins [16]. The effects of fluoroprolines have been examined in a number of protein structures. These studies demonstrated an altered stability and altered folding kinetics that occurred upon the proline-to-fluoroproline replacement, as reviewed in [17]. Nonetheless, no whole-cell

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• ], has dramatically improved the prospects. One of the problems facing the treatment of HCF3 for nucleophilic trifluoromethylation reactions is the low stability of the directly generated CF3 anion (CF3−) for decomposing to difluorocarbene (:CF2) and fluoride (F−) (Scheme 1a). Due to the formation of

Mesoionic tetrazolium-5-aminides: Synthesis, molecular and crystal structures, UV–vis spectra, and DFT calculations

• Vladislav A. Budevich,
• Sergei V. Voitekhovich,
• Alexander V. Zuraev,
• Vadim E. Matulis,
• Vitaly E. Matulis,
• Alexander S. Lyakhov,
• Ludmila S. Ivashkevich and
• Oleg A. Ivashkevich

Beilstein J. Org. Chem. 2021, 17, 385–395, doi:10.3762/bjoc.17.34

• : aminotetrazoles; DFT; mesoionic compounds; UV–vis spectra; X-ray analysis; Introduction 5-Aminotetrazoles are one of the most available and valuable tetrazole derivatives. So, due to the thermal stability and high nitrogen content the parent 5-aminotetrazole (1, Figure 1) is of practical interest as a gas

• thermal stability of the tetrazolium-5-aminides (see Supporting Information File 1 for more details). Some nucleophilic displacement reactions were carried out in order to show the higher reactivity of the aminides in comparison to the parent aminotetrazoles. The high nucleophilicity of the imine group in

• -regioisomers (152–156 and 143.4 ppm for 1-methyl-5H-tetrazole) [31]. The de-tert-butylation selectivity observed for compound 11b can be explained by the higher stability of the t-Bu cation versus the Me cation. Crystal structures The mesoionic compounds 8a, 10, 11a, and salt 9 were characterized by single

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• very poor stabilizing power by π-electron donation. A trend exists in the magnitude of the parameter according to the nature of the carbenium ions, which is in line with the carbenium ion stability (alkyl < allylic < benzylic). Thus, an increased π-electron transfer is present in the least-stabilized

• alkylcarbenium ions, in which a higher electronic contribution from neighboring substituents is required. Detailed ab initio studies have been focused on the stability of the CF3CH2+ cation and provide pieces of thoughts on the origins of the stabilizing interactions in α-(trifluoromethyl)carbenium ions. The

• Letcka et al., which can be seen as a strong nF→2pC interaction (Wiberg bond order of 0.53 for each C–F bond), gave additional credit to these calculations (Figure 1, bottom) [26][27][28]. The thermochemical data can also provide information on the effect of the CF3 group on the stability of the

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• expected, the investigation of the stability of the chromogenic substrate 12 using UV–visible spectrophotometry revealed that, unlike 4-nitrocatechol-1-yl ferulate (4NTC–Fe), which undergoes spontaneous hydrolysis even at a neutral pH value and 40 °C [13], the presence of the alkyl linker procures a higher

• stability over a wide pH value range (up to pH 9.0), irrespective of the temperature. This is because in compound 12, the ferulate moiety is not directly linked to the good leaving group 4NTC (pKa = 6.61 [40]). Instead, it is bonded to the linker with a pKa value that can be compared either to that of

• glycerol (pKa = 13.61) or ʟ-arabinose (pKa = 11.31) [41], meaning that it is a poor leaving group. Moreover, our observations regarding the linker stability are consistent with the known stability of the ester linkages under basic conditions. The usefulness of 4NTC–linker–Fe (12) for the characterization

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• convenient technique to study a range of factors that might influence the plasma and metabolic stability of the lead compounds, proving itself as a valuable alternative to more challenging conventional HPLC or 1H NMR analyses. It is also worth noting that recent investigations within the Dalvit group have

• associated with protein expression, purification, stability, solubility and structural heterogeneity [82][83][84]. In particular, the application of solution NMR techniques to the study of MPs has proven exceptionally challenging due to the slower tumbling rates that MPs experience within membrane mimetics

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• technology. The incorporation of fluorine into molecules can significantly influence their pharmacokinetic and physicochemical properties and enhance their metabolic and chemical stability [1][2][3][4][5]. For instance, nearly a quarter of the currently manufactured agrochemical and pharmaceutical products

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• stability of different redox states both in non-coordinated form and as being a ligand. It is important that these bicyclic dioxolene species exhibit the typical properties of sterically hindered o-quinones, such as redox transformations between o-qiunone, semiquinone and catecholate forms as well as

• stability of the thiete cycle is a consequence of the protective effect of the bulky tert-butyl groups at the quinone ring. o-Quinone 7 has a rigid skeleton, the dihedral angle formed by O(1)–C(1)–C(2)–O(2) (o-quinone) and O(3)–C(11)–O(4) (acetylacetone) chelating sites mean planes is about 67.4(2)°. In

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• the observed product. Only diarylimines were utilized in this study, largely because of their ease of preparation and stability. Ring-opening reaction of gem-difluorocyclopropylstannanes: Konno and co-workers reported the conversion of cyclopropylstannanes 117 into monofluoro derivatives of allylic

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• yield, which, we believe, is related to the stability of the starting materials and the formed products in the reaction media. Furthermore, a benzyl group directly bonded to the ester 1h was also employed under the standard reaction conditions, and after 20 h, benzyl 2-(benzylthio)acetate (3q) was

Exploring the possibility of using fluorine-involved non-conjugated electron-withdrawing groups for thermally activated delayed fluorescence emitters by TD-DFT calculation

• Dongyang Chen and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 210–223, doi:10.3762/bjoc.17.21

• presence of these states helped to explain the short τd of 3.7 μs and the high EQEmax of 17% and good device stability with a T50 of 176 hours for the OLED [CIE coordinate (0.22, 0.40)] [23]. In an analogous manner, TD-DFT calculations predicted 5CzTRZ to possess a small ΔEST (0.02 eV) as well as a small

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• alter the ternary system through external triggering are accessible. The structure and trigger effects can be controlled through the component ratios of the samples. Dynamic and static light scattering (DLS, SLS) and ζ-potential measurements were applied to study the size and the stability of the