Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• biomedical applications, in particular as an alternative to the hydrophilic poly(ethylene glycol) (PEG), which is the polymer of choice for many biomedical applications due to its high solubility, low cytotoxicity and biocompatibility [3][4][5][6][7][8][9]. However, an ongoing discussion about pre-existing

• /or initiator did not yield considerable improvements. It is known that MeOx polymerization can be challenging due to the poor solubility of PMeOx in some solvents [30][31][34]. However, no precipitation was observed during polymerization, which rules out the solubility as an issue. Therefore, we

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• ). Accordingly, the internal double bond in 25a stayed unaffected whereas the triple bond, as expected, selectively formed the double bond with (E)-configuration. Note that a reaction temperature of 50 °C is required in the first step of the sequence to obtain rapid solubility of the Schwartz reagent in the

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• improve solubility and metabolic stability while retaining potency [5]. Late-stage functionalisation (LSF) is a strategy involving the use of C–H bonds as chemical handles for the introduction of various functional groups, which has been widely employed by medicinal chemists to generate new analogues of

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• the reactivity of a thiophene-fused dihydropyridine as a cyclic imine. The tricyclic α-methylene-γ-lactam product 19k was obtained in 40% yield and as single diastereomer. It should be noted that due to the low solubility of the imine substrate in CH3CN, this reaction was carried out in CH2Cl2 at 23

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• further by increasing the charge (Table 2, entry 5). For a final combination of the two reaction steps, benzyl acetate 3a was chosen as a model substrate due to its high solubility and good reactivity as was previously demonstrated by us (Table 3) [28]. We determined an optimal reaction time of 20 min for

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• Alexios I. Vicatos Zakiena Hoossen Mino R. Caira Centre for Supramolecular Chemistry Research (CSCR), Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa 10.3762/bjoc.18.184 Abstract Overcoming the challenges of poor aqueous solubility of active pharmaceutical

• ingredients (APIs) is necessary to render them bioavailable. This study addresses the poor solubility of two potent steroid hormones, 17β-estradiol (BES) and progesterone (PRO), via their complexation with two water-soluble native cyclodextrins (CDs) namely β-CD and γ-CD. The hydrated inclusion complexes β

• 1H NMR spectroscopy. Subsequent measurements of the aqueous solubilities of the four complexes confirmed significant solubility improvements effected by encapsulation of the steroids within the CDs, yielding solubility enhancement factors for BES and PRO in the approximate range 5–20. Keywords

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• reducing agent sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al®), which is a convenient alternative to LiAlH4 that exhibits high solubility in organic solvents and is also known to reduce amides [17]. When a solution of amide 5 in toluene was treated with an excess of Red-Al® at 0 °C, rapid gas

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• alcohol. We build on a commercially available imidazopyridine derivative and conceived a protecting group strategy to enhance solubility and selectivity to orchestrate the installation of the exocyclic amino and hydroxy groups. Results and Discussion 1-Deazaguanine Previously described syntheses for 1

• be easily prepared from its commercially available 6-chloro derivative [16]. To enable C–O coupling with benzyl alcohol, protection of the N9 with a tetrahydropyranyl group was necessary due to limited solubility of the aryl iodide. Therefore, 6-iodo-1-deazapurine was treated with tosylic acid and

• the cross coupling reaction. We also mention that we did not decide for a direct transformation [27][28] of 6-iodo-1-deazapurine into 6-hydroxy-1-deazapurine for reasons of solubility and desired regioselectivity of the subsequent nitration reaction. 1-Deazahypoxanthine Synthesis of 1

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• 1H NMR and NOESY NMR imply the dependence of molecular symmetry on the type of spacer. The ability of synthesized dimers to increase the solubility of tetracene in DMSO was evaluated and compared to native cyclodextrins and their methylated derivatives. The newly synthesized compounds expressed

• substituted rims are partially methylated CDs. Methylation reduces the formation of intramolecular hydrogen bonds, enhancing CDs water solubility, and also extends the hydrophobic cavity, thus improving its binding potential. A substantial increase of binding constant (K) for per-6-methylated CD compared to

• native CD was described, but an order of magnitude decrease of K was found for permethylated CD [2]. Also, methylation changes the solubility of CDs in organic solvents, expanding their potential field of application. CDs form the most stable complexes with hydrophobic compounds in polar solvents such as

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• diblock copolymer. Binding between the integrin receptor and the RGD peptide on the polymer increased the solubility of the polymer above the associated electrodes and in so doing increased the current associated with the mediator. This change in current relative to the concentration of integrin in

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• furnished the tricyclic compound 8v in 84% yield. In contrast, the reaction with 3-amino-2-anthracenol resulted in a low yield of the tetracyclic compound 8w due to the low solubility of aminoanthracenol. The reaction of 2a with 2-aminothiophenol instead of 2-aminophenol proceeded smoothly, and the

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• due to the strong electron-withdrawing effect of bromine, enhancing the electrophilic property of bromo-substituted salicylaldehyde. Because of the poor solubility in the eluent, the yield of dichloro-containing 1c (88%) was lower than 1a after isolating by column chromatography. This was also found

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• , current trends are found in reports from the industry. A paper from Novartis describes that solubility and cell permeability are, for phenotype-based screenings, the favorite criteria along with structural diversity in regard with previously observed biological effects [86]. Along with such parameters, a

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• various organic molecules have been described so far. It was proved that the complexation of volatile organic compounds, such as aldehydes, into the CD’s cavity reduces the volatility and increases the solubility and bioavailability of these compounds [5][6][7][8][9][10][11][12][13][14]. The release of

• phosphate buffer solutions of pH 1.08, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 9.00, 10.00 11.00, 12.00, and 12.80 were prepared (see Experimental section) using deuterium oxide instead of water to facilitate NMR spectroscopy experiments. Because of the low solubility of the pro-fragrance in water, it had

• of a pH meter. Because of the poor solubility of the pro-fragrance in water, it had to be dissolved in 0.5 mL of deuterated dimethyl sulfoxide. Then, the buffer solutions (0.5 mL) were added and mixed just before starting the measurements. The samples were kept at ambient temperature (20–25 °C

Make or break: the thermodynamic equilibrium of polyphosphate kinase-catalysed reactions

• Michael Keppler,
• Sandra Moser,
• Henning J. Jessen,
• Christoph Held and
• Jennifer N. Andexer

Beilstein J. Org. Chem. 2022, 18, 1278–1288, doi:10.3762/bjoc.18.134

• soluble enzymes and could be easily purified via Ni-NTA affinity chromatography using N-terminal His-tags, the PPK1 enzymes required an N-terminal maltose binding protein (MBP-tag) to improve solubility [46][47]. Trials to cleave the MBP-tag were unsuccessful and resulted in inactive protein aggregates

Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

• Wei-Hsin Hsu,
• Susanne Reischauer,
• Peter H. Seeberger,
• Bartholomäus Pieber and
• Dario Cambié

Beilstein J. Org. Chem. 2022, 18, 1123–1130, doi:10.3762/bjoc.18.115

• concentration as in the original batch report [28]. This was unlike the C–S coupling, where the limited solubility of the sulfinate salt required a dilution of the reaction conditions to obtain a homogenous reaction mixture. As previously observed [28], the reaction concentration has a significant impact on the

Electrochemical Friedel–Crafts-type amidomethylation of arenes by a novel electrochemical oxidation system using a quasi-divided cell and trialkylammonium tetrafluoroborate

• Hisanori Senboku,
• Mizuki Hayama and
• Hidetoshi Matsuno

Beilstein J. Org. Chem. 2022, 18, 1040–1046, doi:10.3762/bjoc.18.105

• likely nucleophile in this reaction medium was the trifluoroacetate ion, which was produced by electrochemical reduction of TFA at the cathode, although we could not detect the coupling product of trifluoroacetate and the corresponding N-acyliminium ion due to the high solubility in water. In addition to

• M iPr2NHEtBF4 using a quasi-divided cell gave 3-amidomethylated N-methylindole 9 in 47% 1H NMR yield and 44% isolated yield at full conversion (Scheme 4). The moderate yield of 9 is thought to be due to its high solubility in water. A probable reaction pathway is shown in Scheme 5. The present

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• recycle them, good stability, low flammability, good solubility ability for many molecules, salts and gases, the possibility to use them as reagents and/or solvents, large electrochemical window, good electrical conductivity, their ionic nature sometimes increases the reactivity and the selectivity of

Introducing a new 7-ring fused diindenone-dithieno[3,2-b:2',3'-d]thiophene unit as a promising component for organic semiconductor materials

• Valentin H. K. Fell,
• Joseph Cameron,
• Alexander L. Kanibolotsky,
• Eman J. Hussien and
• Peter J. Skabara

Beilstein J. Org. Chem. 2022, 18, 944–955, doi:10.3762/bjoc.18.94

• -withdrawing keto groups. To enable solubility in common organic solvents, the fused system is flanked by ethylhexylthiophene groups. The material is a dark, amorphous solid with an onset of absorption at 638 nm in CH2Cl2 solution, which corresponds to an optical gap of 1.94 eV. In films, the absorption onset

• to poor solubility as a consequence of strong π–π interactions between the planar molecules [4]. Thus, attaching solubilising alkyl chains is necessary [5]. A common way to further decrease the HOMO–LUMO gap is attaching electron-donating and electron-accepting groups. Electron-rich units raise the

• a certain application, for example where charge transport is more important than photoluminescence quantum yield or vice versa. Introducing alkyl chains can provide solubility, enabling facile solution processing, such as device printing techniques [13]. Hence, there is an ongoing interest in

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• , plausibly because of a degree of water solubility of the ammonium salts of compound 3{1,1} and 4{1,1}. The effect of using triethylamine instead of sodium hydroxide as a base was remarkable. At room temperature, after an 18 hours-long reaction, hydroxypyrazine 4{1,1} was the sole isomer detected and, out of

• the one obtained at −78 °C (Table 2, entry 19). Concerning the structural attribution of the hydroxypyrazines isolated in Table 1 and Table 2, the use of our unambiguous synthetic route to prepare compounds 3{1,1} [34] or 3{1,2} [29] secured these issues. However, since a real lack of solubility for

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• acceptors Some Lewis acids have good solubility in common organic solvents, which makes it easy to fabricate films for optoelectronic applications [24]. Because of their strong electrophilicity [25], Lewis acids may dominate charge distributions of the fluorescent materials featured with electron-rich

• acids B(C6F5)3 and B(C6H5)3 as electron acceptors, respectively [29]. B(C6F5)3 displays high chemical stability and Lewis acidity [30]. Moreover, its good solubility endows the possibility to form Lewis acid–base adducts in films by solution processing. The strong electron attraction of the fluorine

• –base treatment, the polymer film can achieve reversible color changing. Due to the poor solubility, the doped polymer film was simply prepared by BF3 vapor treatment. The schematic diagram is shown in Figure 4. It is clear that the film achieved a gradient of colors from top to bottom under 365 nm UV

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• solubility of this class of molecules, perfluoroalkyl iodides have a tendency to be weakly soluble in common organic solvents (i.e., ethyl acetate and methanol) rendering their application troublesome [9]. Moreover, the homolysis of the perfluoroalkyl iodide produces iodine radicals that can result in stray

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• due to their specific characteristics such as basicity, hydrogen bond forming ability, water solubility, and especially because of pyridine rings are bioisosteres of amines, amides, N-heterocyclic rings and benzene rings [1][2][3][4][5]. A special type of pyridine, the 4-pyridones, is also fairly well

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• prenyltransferase; Introduction Marine bacteria harbor an enormous potential to produce structurally diverse natural products, including prenylated aromatic metabolites [1][2]. Prenylation of metabolites most often confers increased biological activities due to enhanced lipophilicity, solubility, and improved

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• materials to inductively heat up glass reactors. For the Biginelli reaction solubility of the starting urea (22) as well as the products 24a and 24b were an issue being overcome by using a solvent mixture of PEG/DMF 1:1. Also the proline-catalyzed asymmetric Mannich reaction was achieved with cyclohexanone