N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• [70]. The reactions were performed in THF at −78 °C, using lithium hexamethyldisilazide as base. Aziridines with relative trans-configuration were obtained in good yields and excellent stereoselectivities with methyl α-bromo-α-phenylacetate (26, R2 = Ph). Lower yields, and poorer

• an intramolecular nucleophilic substitution of the tosylate of the resulting primary alcohol (Scheme 15). This methodology was applicable to the synthesis of 1-phenyl-2-azaspiro[3.4]octane (45, n = 2, R = Ph) and 1-phenyl-2-azaspiro[3.5]nonane (45, n = 3, R = Ph). The structure and absolute

• successively into β-amino esters 51, and the corresponding β-lactams 52 with high optical purity (Scheme 17) [89]. The absolute configurations of compounds 52 were obtained by the comparison of the signs of specific rotation of 52 with R = Ph(CH2)2, with that of known (R)-4-(2-phenylethyl)azetidin-2-one. A 6/4

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

• 3100–3400 cm−1 for the N–H bonds vibrations. NMR spectra record specific signals at 6.8–7.5 ppm for the shifts of the protons and 158–165 ppm for the 13C. Biguanides are good nucleophiles and easily carbonated under ambient conditions. They are stable over a wide range of pH. Often, heating in the

• reaction times, Cohn’s method remains a valid protocol to access N1-aryl- and alkylbiguanides. As a representative example, Böttcher et al. recently described the addition of 1,3-diaminobenzene to two equivalents of cyanoguanidine at low pH in aqueous hydrochloric acid to produce the corresponding

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• GmbH (Ulm, Germany). Oligonucleotides were dissolved in K-phosphate buffer, and the solution was heated to 95 °C for 5 min and then cooled slowly to room temperature within 4 h. K-phosphate buffer: 25 mM K2HPO4, 60 mM KCl; adjusted with 50 mM KH2PO4, 60 mM KCl to pH 7.0; BPE (biphosphate EDTA) buffer

• : 6.0 mM Na2HPO4, 2.0 mM NaH2PO4, 1.0 mM Na2EDTA; pH 7.0. All buffer solutions were prepared from purified water (resistivity 18 MΩ cm) and biochemistry-grade chemicals. The buffer solutions were filtered through a PVDF membrane filter (pore size 0.45 μm) prior to use. Structures and numbering of

• : Plots of the relative fluorescence intensity versus the temperature of the solution. Photometric titration of 5a (A) and 5d (B) (cLigand = 20 μM) with ct DNA (1) in BPE buffer (cNa+ = 16 mM, pH 7.0, with 5% v/v DMSO) and with 22AG (2) in K-phosphate buffer (cK+ = 110 mM, pH 7.0, with 5% v/v DMSO). The

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

• sequence and base composition [65]. The presence of alternating phosphodiester and phosphoramidate linkages within an oligonucleotide resulted in improved binding to RNA relative to DNA. Homopyrimidine 3'-NP DNA forms a stable triplex at neutral pH with double-stranded DNA and RNA [64][65][66]. These

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• under vacuum. The lipid film was dissolved in ethanol (20.3 mg/mL) and added dropwise to stirring 50 mM citrate buffer at pH 4.0 and preheated to 35 °C to get a final lipid concentration of 6.1 mg/mL. The lipid solution was stirred for an additional 20 min at 35 °C, after which the lipid solution was

• allowed to slowly reach rt, transferred to a 1 mL Hamilton syringe, and extruded 10 times at rt through two 100 nm Nucleopore membrane filters (Whatman) using Avanti Mini Extruder (Avanti Polar Lipids, Inc., USA). Complementary oligonucleotides GP160:A-1 (1.4 nmol, 30 μL 1× PBS pH 7.4) and CCR5:G-3 (1.4

• nmol, 30 μL 1× PBS pH 7.4) underwent annealing (85 °C for 10 min, 25 °C for 20 min, 4 °C for 20 min). GP160:A-1 (30 μL) and CCR5:G-3 (30 μL) were each added to a stirring LNP suspension (6.1 mg/mL, 165 μL) preheated to 35 °C, and LNP–DNA lipoplex suspensions were further diluted with 50 mM citrate

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• reduction of simple ketones by NADH at pH around 7.5 [35]. Effect of the initial starting material concentration and enzyme E value for “ordered, second” kinetics. D = 0.00333 M, Q = 0.00167 M, Keq = 5, E = 39, KMD = 0.001 M, KMS = 0.001 M, k4 = 1000 s−1, SCRf/b = 1, k3R/k4 = 1, k3R/(E · k3S) = 1, k−4/k1

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• , in addition to ethylene glycol 1.0 mL of water was added to the mixture and we were pleased to find that compound A smoothly decomposed at 95 °C in 3.5 h. With the decline of compound A in the toluene layer, a new compound C2 emerged. It was also noticed that the pH value of the ethylene glycol layer

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

• the purified, desalted, and lyophilised ONs were fully dissolved in 50 µL H2O. The Ts-modified ONs have previously been shown to marginally destabilise duplexes with complementary DNA and RNA [39]. The chemical stability of 5ʼ-N+ON2 at various pH (5.5, 7.0, and 8.5) was evaluated by incubation in 10

• number of N+ and Ts modifications were studied initially in an antiparallel duplex formed with complementary RNA and compared with the corresponding antiparallel DNA duplexes at pH 7.0. Apart from the ONs possessing modifications in the middle of the sequence (entries 6, 9, and 12 in Table 2), stabilised

• destablised the DNA duplex at pH 5.0. The destablising effect was more pronounced for Ts than for the N+ modification (ΔTm = −17 to −4 °C for Ts and −5 to 0 °C for N+ modifications, respectively). For the antiparallel ON/DNA duplexes formed at pH 7.0, when comparing ONs with the same number of modifications

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• linear chain comprising of up to four monosaccharide units, containing glucose, galactose and N-acetylgalactosamine, to which are attached a variable number of sialic acid (N-acetylneuraminic acid) residues. The sialic acid content of the oligosaccharide, being anionic at pH 7, results in an overall

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• , antihypertensive, anti-Parkinson, anti-inflammatory, anticonvulsant, vasodilatory, antidiabetic, antitubercular, antifungal, and antibacterial activities [32][33][34][35][36][37][38], pH-sensing [39], OLEDs [40], chemiluminescent materials [41][42], metal complexes (Figure 1) [43][44][45][46], liquid crystal [47

• electron-withdrawing groups (EWGs) 2a–f (4-pyridyl, 3,5-dimethyl-1H-pyrazol-1-yl, CONH2, CN) resulted in the formation of the target molecules 3a–f in high yields. However, the reactions of tetrazine derivatives with electron-donating groups (EDGs) 2g–j (Ph, OMe, NH2, NHAc) did not work under the same

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

• acetate buffer (pH 7.0). The purity and structure of the oligonucleotides were confirmed by HPLC and MALDI–TOF mass spectrometry, respectively. UV melting experiments and melting profiles The UV melting experiments were carried out using SHIMADZU UV-1650PC and SHIMADZU UV-1800 spectrometers equipped with

• a Tm analysis accessory. Equimolecular amounts of the target ssRNAs or ssDNAs and the oligonucleotides were dissolved in 10 mM sodium phosphate buffer (pH 7.2) containing 100 mM NaCl to achieve a final strand concentration of 4 µM. The samples were annealed by heating at 95 °C followed by slow

• , and path length in centimeters, respectively. Structures of 2',4'-BNA/LNA analogs. The CD spectra of the ON7/ssRNA, ON2/ssRNA, ON7/ssDNA, and ON2/ssDNA duplexes. Conditions: 10 mM sodium phosphate buffer (pH 7.2), 100 mM NaCl, 4 µM each oligonucleotide. Sequences of the complementary ssRNA and ssDNA

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

• )piperazine-N′-(2-ethanesulfonic acid), powder, 99.5%, Corning, NY) buffer solution (20 mM) in 150 mM NaCl was prepared and adjusted to pH 7.4 using 0.1 N NaOH. Chloroform (99.4%) was purchased from VWR (Avantor, Fontenay-sous-Bois). Ultrapure water was obtained from a Milli-Q (Millipore Corp.) system

• ; purity (retention time): >99% (13.9 min). Adsorption kinetics of lipopeptides at the air/water interface. The experiments were conducted in a home-made Teflon adsorption trough (11.9 × 5.0 × 0.3 cm3) filled with HEPES buffer (pH 7.4). The surface pressure π was measured using the Wilhelmy plate method

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

• around peptidyl-prolyl [56]. Some other common factors, such as the pH value or the ionic strength, are believed to have a very minor, if any, influence [53]. The enhancement of the amide rotation rate by fluoroprolines can have an effect on the overall protein folding velocity. An impairment of the

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• for 40 min, the reaction was quenched with phosphate buffer (pH 7). Organic materials were extracted with CH2Cl2 three times, and the combined extracts were washed with brine and dried over Na2SO4. After removal of the solvents under reduced pressure, the residue was purified by silica gel column

• with phosphate buffer (pH 7). Organic materials were extracted with ethyl acetate three times, and the combined extracts were washed with brine and dried over Na2SO4. After removal of the solvents under reduced pressure, the residue was purified by silica gel column chromatography (hexane/CH2Cl2 = 3:1

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

• HClO4 (3 ≤ pH ≤ 4) and mentioned that this low value is “typical of a preequilibrium protonation reaction” and the rate-limiting solvolysis of diazonium ion 218a (Figure 10b

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• and B, are related as 7a-epimers that interconvert in aqueous solution to form a pH-dependent equilibrium ratio of the two [9]; they are weakly antibacterial and were shown to prolong “the survival period of mice inoculated with leukaemia L-120 cells” [7][8]. Although the clazamycins are not

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

• /L ammonium chloride, 20 mL/L oleic acid, 10 g/L ᴅ-glucose, 2 g/L casamino acid, and 15 g/L bacto agar in 100 mM citrate–phosphate buffer at pH 5). The petri dishes were incubated for 48 h at 30 °C and then overlayered with a preparation of 1% (w/v) molten top agar containing the chromogenic

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

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

• pH-responsive nano-assemblies with switchable size and structure are formed by the association of a photoacid, anthocyanidin, and a linear polyelectrolyte in aqueous solution. Specifically, anionic disulfonated naphthol derivatives, neutral hydroxyflavylium, and cationic poly(allylamine) are used as

• can respond to external triggers including pH change [41][42][43], light [44][45][46][47][48][49][50], electrochemical stimuli [51][52], and temperature [53][54]. Of particular interest is the responsivity to light due to its non-invasiveness, which can be achieved with molecules that undergo

• , pH, and temperature. In this respect, it is highly desirable to establish novel supramolecular nanoscale structures in aqueous solution that can respond to multiple triggers. Herein, we studied a multi-responsive system based on the self-assembly of a cationic polyelectrolyte and two organic

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• the use of a substrate similar to 2a where the CF3 and Ph groups were formally exchanged, an isolated yield of 84% has been recorded for 6ca [37]. Moreover, it is noteworthy that only one report dealt with the preparation of 6cb [37], and 6cc and 6cd have not been previously reported. Thus, including

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• counteracts the β-sheet-driven self-assembly due to electrostatic repulsion. CD spectroscopic experiments based on 25 µM or 50 µM solutions of II in 20 mM TRIS as well as PBS buffer support this notion (Figure 2A and Figure S2 in Supporting Information File 1). In pure 20 mM TRIS buffer (pH 7.4) the β-sheet

• decided to perform ionic strength-dependent titrations using a 25 µM solution of II in 20 mM TRIS at neutral pH. At >100 mM added NaCl, the characteristic β-sheet signature is restored due to charge screening of the peripheral sulfate groups (Figure 2A and Figure S3 in Supporting Information File 1

• ). These results are in agreement with our previous investigations related to pH-switchable and ionic strength-responsive dendritic amphiphiles appended with dendritic carboxylic acid functionalities [40][41]. The physiological ionic strength thus efficiently screens the repulsive contribution of the

Control over size, shape, and photonics of self-assembled organic nanocrystals

• Chen Shahar,
• Yaron Tidhar,
• Yunmin Jung,
• Haim Weissman,
• Sidney R. Cohen,
• Ronit Bitton,
• Iddo Pinkas,
• Gilad Haran and
• Boris Rybtchinski

Beilstein J. Org. Chem. 2021, 17, 42–51, doi:10.3762/bjoc.17.5

• carboxylate groups that are expected to favor the solvation by water. We induced the self-assembly process by injecting a concentrated solution of 1 in THF (2 × 10−3 M) into basic water (pH 10) or a water/THF mixture to reach a 1 × 10−4 M concentration. We studied the following three assembly conditions: “10

• hydrophobic self-assembly). We noted that at a lower pH (Figure S8, Supporting Information File 1), the self-assembly leads to different structures, probably due to the lower solubility and interactions between the protonated carboxylic groups. Crystals assembled under different pH conditions (Figure S8

• have demonstrated that a simple building block assembles into well-defined free-floating crystals in an aqueous medium. The crystalline assemblies are stable and their morphology can be fine-tuned as a function of the initial THF concentration or the pH in the assembly solution. The nanocrystals

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• ) amberlyst-15 resin, MeOH; iii) 1. n-BuLi; 2. TMSCl, 3. HCl aqueous, 76% over 3 steps; iv) oxalyl chloride, DMSO, Et3N, 80–90%; v) CH2=CHCH2MgBr, Et2O, 70–81%; vi) 1. CrO3, HOAc; 2. NH2OH·HCl, Py–EtOH, 58–66%; vii) NaCNBH3, MeOH, pH 3–4; viii) toluene, reflux, 9 h, 71–76%; ix) Raney-Ni, H2, 90 min, 93–96%; x

The fluorescence of a mercury probe based on osthol

• Guangyan Luo,
• Zhishu Zeng,
• Lin Zhang,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2021, 17, 22–27, doi:10.3762/bjoc.17.3

• (n = 7, where σ is the standard deviation and K is the slope of the calibration curve) [27], the detection limit of the OST probe for Hg2+ was 5.04 × 10−8 mol∙L−1. Impact of the pH value of the solution The effects of the pH value on the fluorescence intensity of the system are shown in Figure S1

• , Supporting Information File 1. The fluorescence intensity of the OST probe was weak in the pH value range of 2–10. When Hg2+ was added, the fluorescence intensity of OST–Hg2+ was strong, and stable in the pH value range of 4–10. Especially at pH 4–8.0, the fluorescence intensity reached the maximum value

• . Therefore, we chose pH 4–8.0 as the best measurement conditions. Effect of the solvent Figure S2 in Supporting Information File 1 shows the effects of different solvents on the fluorescence intensity of OST and OST–Hg2+. The results showed that the fluorescence intensity of OST was relatively weak in the

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• in the protein molecules due to proton uptake and release. Therefore, these events are strongly affected by the pH value and the ionic strength. Variation of the pH value or the ionic strength can result in substantial binding free energy changes [48] or changes in the binding preference [49

• ], producing two different modes of binding: pH-dependent and salt-dependent binding mechanisms. In a pH-dependent binding mechanism, an overall proton is either released or taken up during the protein interaction due to the binding-induced pKa shift of acidic or basic amino acids present at the complex

• interface. Due to this shift, the interface amino acids experience either a significant desolvation energy, where there is a disruption in the residue charge–water interaction, resulting in water exclusion, and thus a hydrophobic effect [50], or an interaction in the complex formation. An example of the pH