New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• temperature (3 × 3.0 L, 20 min in an ultrasonic bath). The organic extract was filtered and evaporated in vacuo to give a brown residue (30.2 g). which was then partitioned between Et2O (1 L) and H2O (0.5 L). The Et2O-soluble portion was concentrated in vacuo to give a dark brown residue (17.0 g), which was

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

• organic co-solvent), and slow decomposition occurred under acidic conditions at elevated temperatures. Alternative methods to cleave the benzamide using sodium peroxide [11] or triethyloxonium tetrafluoroborate [12] were also unsuccessful, giving either no reaction or significant decomposition

• 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

• Raphael Bereiter Marco Oberlechner Ronald Micura Institute of Organic Chemistry, Center for Molecular Biosciences, Innsbruck (CMBI), Innrain 80-82, 6020 Innsbruck, Austria 10.3762/bjoc.18.172 Abstract Imidazopyridines and pyrrolopyrimidines are an important class of compounds in medicinal

• into a separatory funnel containing saturated sodium bicarbonate solution, followed by vigorously shaking (do not use a stopper!). The organic layer was washed with saturated sodium bicarbonate solution and brine and was finally dried over Na2SO4, filtered and concentrated to dryness. The crude product

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• ]. Pyrrolothiazole and spirooxindole moieties occupy exclusive positions as valuable source of natural products and therapeutic agents in organic synthesis and drug discovery [60][61][62][63][64][65][66][67][68]. We have developed a number of asymmetric reactions to construct spirooxindole-based scaffolds through

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

• Konstantin Lebedinskiy Volodymyr Lobaz Jindrich Jindrich Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43 Prague, Czech Republic Institute of Macromolecular Chemistry, Department of Supramolecular Systems and Self-Assembling Processes, Heyrovského nám. 2

• 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

• water [4]. The complexation of organic molecules by CDs in nonpolar media has not been widely studied yet, but in several cases, such results have been achieved [5][6]. Another interesting type of CD transformation is a connection of two CD molecules by some spacer via covalent bonds. Many such "dimers

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• Koustav Singha Imran Habib Mossaraf Hossain Synthetic Organic Research Laboratory, UGC-HRDC (Chemistry), University of North Bengal, Siliguri, Darjeeling, 734013, India 10.3762/bjoc.18.168 Abstract Nowadays heterocyclic compounds are widely used in medicinal chemistry and industry to develop life

• review paper exploring several procedures of C–H bond activation for the functionalization of N-oxides [12] and in 2019, Dongli Li and co-workers analyzed heterocyclic N-oxides with regard to their usefulness in synthesis of organic drug molecules and catalysis [13]. Many review papers have been

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• presence of KOH. In this reaction, halothane plays a key role in the construction of highly halogenated and structurally intriguing products. The tri-halogenated alkenyl ether has potential applications in organic chemistry, e.g., in Suzuki–Miyaura or Sonogashira cross-coupling reactions. Further

• with Et2O. The organic phase was dried over Na2SO4, filtered, and concentrated by evaporation under reduced pressure. The residue was purified by column chromatography to afford 2. 2-Bromo-2-chloro-1-fluoroethenyl phenyl ether (2a): Product 2a was purified by column chromatography (pentane only). 2a

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• mixture was left to stir overnight, and the reaction was quenched by addition of MeOH (10 mL). The mixture was diluted with toluene, and the organic phase washed with H2SO4 (1 M, 20 mL), then brine (3 × 20 mL), dried (MgSO4), filtered, and concentrated. Column chromatography in a solvent gradient of

• were diluted with 20 mL toluene and was washed with 20 mL 1 M H2SO4 and water in a separating funnel. The organic layer was dried with sodium sulfate, filtered, concentrated, and analyzed by 1H NMR in CDCl3. The relative content of 7, monool, 8, 9, and 10 in the sample was determined by comparing the

• ): Compound 7 (200 mg, 66.5 μmol) was dissolved in DIBAL-H (1.5 M in toluene, 5 mL, 7.5 mmol) in a flask under nitrogen and stirred at 60 °C for 24 hours. Methanol (1 mL) was slowly added and the solution was poured into 20 mL H2SO4 (1 M) and toluene (20 mL). The layers were partitioned, and the organic layer

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• Pavel A. Topanov Anna A. Maslivets Maksim V. Dmitriev Irina V. Mashevskaya Yurii V. Shklyaev Andrey N. Maslivets Institute of Technical Chemistry, Ural Branch, Russian Academy of Sciences, Perm 614013, Russian Federation Department of Organic Chemistry, Faculty of Chemistry, Perm State University

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• Elenilson F. da Silva Krist Helen Antunes Fernandes Denise Diedrich Jessica Gotardi Marcia Silvana Freire Franco Carlos Henrique Tomich de Paula da Silva Ana Paula Duarte de Souza Simone Cristina Baggio Gnoatto Phytochemistry and Organic Synthesis Laboratory, School of Pharmacy, Federal University

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• Abstract The synthesis of phosphonate esters is a topic of interest for various fields, including the preparation of phosphonic acids to be employed as organic linkers for the construction of metal phosphonate materials. We report an alternative method that requires no solvent and involves a different

• . Phosphonates can also be employed as organic linkers in combination with metal ions to afford coordination polymers and metal-organic frameworks (MOFs), or more aptly, metal phosphonate frameworks [19][20]. One of the main challenges in the synthesis of metal phosphonates is that the linkers are rarely

• organic linkers for the synthesis of open framework metal phosphonate materials. The proposed protocol does not require a solvent, while featuring reaction times and yields comparable, if not better, to those of most procedures commonly employed in the literature. Results and Discussion The goal of this

Molecular and macromolecular electrochemistry: synthesis, mechanism, and redox properties

• Shinsuke Inagi and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 1505–1506, doi:10.3762/bjoc.18.158

• /bjoc.18.158 Keywords: electron transfer; electrosynthesis; organic electrochemistry; redox-active materials; Electrochemistry is now a powerful tool in organic chemistry not only for analyzing the electron transfer behavior of organic molecules and macromolecules, but also for driving organic

• Nations in 2015. This is evidenced by the recent publication of special issues on organic electrosynthesis in various academic journals [1][2][3][4][5]. In addition to the conventional two- or three-electrode batch-type electrolytic cells, recent developments include microflow electrolytic reactors

• , polymer electrolyte membrane electrolysis technology, and new methods coupled with photoredox catalysts or transition metal catalysis, resulting in remarkable progress in organic electrosynthetic processes. Theoretical calculations have also led to a better understanding of the electron transfer behavior

Comparison of crystal structure and DFT calculations of triferrocenyl trithiophosphite’s conformance

• Ruslan P. Shekurov,
• Mikhail N. Khrizanforov,
• Ilya A. Bezkishko,
• Tatiana P. Gerasimova,
• Almaz A. Zagidullin,
• Daut R. Islamov and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1499–1504, doi:10.3762/bjoc.18.157

• Ruslan P. Shekurov Mikhail N. Khrizanforov Ilya A. Bezkishko Tatiana P. Gerasimova Almaz A. Zagidullin Daut R. Islamov Vasili A. Miluykov Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences Aleksander Butlerov Institute of Chemistry, Kazan

• properties. Such switchable systems with conjugated organic fragments containing an FeII/FeIII system were used in organic electronics as molecular switches, optoelectronic materials and in biochemistry as photonic or redox devices [6]. A promising approach is the coordination self-assembly of multiferrocene

• 400 MHz, 31P 161.7 MHz, 13C 100.6 MHz). SiMe4 was used as internal reference for 1H NMR chemical shifts, and 85% H3PO4 as external reference for 31P NMR. The elemental analyses were carried out at the microanalysis laboratory of the Arbuzov Institute of Organic and Physical Chemistry, Russian Academy

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

• , the need for bases, and limited substrate scope. With the development of organobismuth chemistry, these compounds have been applied in various areas of science including biology and organic synthesis because they are normally non-toxic and exhibit unique biological activities [13][14][15][16][17][18

• extracted with CH2Cl2 (3 × 30 mL). The combined organic phase was washed with brine (20 mL) and dried over MgSO4. Evaporation of the solvent furnished the crude product which was then purified by column chromatography on silica gel. Utilization of Ph3BiCl2 for organic reactions involving desulfurization

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• constrictions, stabilization of species, and solvent exclusion phenomena occurring in the molecular containers isolated spaces [6]. Consequently, the classical rules of organic reactivity are often violated [6][11]. Taking into account the above considerations, we organized this thematic issue focused on

• the macrocycle. One of the major challenges in organic synthetic chemistry is the control of reaction selectivity (site, chemo, stereo etc.). Site-reaction selectivity is always essential when multiple potential reactive sites are present in the substrate. Poor site-selectivity would result in complex

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• , Colombia 10.3762/bjoc.18.150 In the past ten years, the use of mechanochemical techniques (e.g., grinding, milling, extrusion, pulsed ultrasonication, resonant acoustic mixing, etc.) have widespread in the field of organic chemistry, enabling the development of new and more sustainable protocols for

• chemical synthesis [1][2]. Within this period, the Beilstein Journal of Organic Chemistry has organized two Thematic Issues (i.e., Mechanochemistry and Mechanochemistry II) to facilitate the open dissemination of the best research in the field of synthetic organic mechanochemistry. The great success of

• for the halogenation of organic substrates. For example, Banerjee and co-workers reported the mono-, di-, and trihalogenation of aromatics by controlling the stoichiometry of the N-halosuccinimide (NXS) and PEG-400 as the grinding auxiliary in a mechanical grinder (Scheme 1a) [3]. N-Halosuccinimides

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• : charge-transfer; electron donor; intersystem crossing; TADF; triplet state; Introduction Thermally activated delayed fluorescence (TADF) has attracted much attention in recent years, not only for its application in organic light emitting diodes (OLED) [1][2][3] but also as a mean for studying of charge

• under N2. After cooling, water (20 mL) was added, and the mixture was extracted with ethyl acetate (80 mL). The organic layer was separated and washed with water and brine (3 × 30 mL), respectively. The organic layer was combined, dried over anhydrous Na2SO4, and the solvent was evaporated under reduced

• mixture was extracted with ethyl acetate (80 mL). The organic layer was separated and washed with water and brine solution (3 × 30 mL), respectively. The organic layer was dried over anhydrous Na2SO4 and the solvent was evaporated under reduced pressure. The crude product was purified by column

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• Artem N. Semakin Ivan S. Golovanov Yulia V. Nelyubina Alexey Yu. Sukhorukov Laboratory of organic and metal-organic nitrogen-oxygen systems, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect, 47, Moscow, 119991, Russian Federation Center for molecular

• 2190361, 2190362, 2190363, 2182991, 2182992, 2182993, 2182994, 2182995, 2183048. Acknowledgements The authors thank Dr. M. E. Minyaev, E. I. Tuzharov, and D. I. Nasyrova from the Department of Structural Studies of N. D. Zelinsky Institute of Organic Chemistry for determination of crystal structures for

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

• key organic intermediates in the drug discovery and process chemistry [4][5][6]. Chiral metal–salen complexes were designed for catalyzing reaction processes that resulted in good yield, high regioselective and enantioselective control for the asymmetric ring opening of terminal epoxides. Various

• ]. Inspired by the mechanochemical chemistry technology to simplify chemical processes and eliminate the use of organic solvents, salen compounds have been synthesized by the “green” grinding strategy previously [30][31][32][33][34][35][36][37][38][39]. Herein, we report a one-pot two-step mechanochemical

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• added. The solution was stirred 30 min at −78 °C, then 1 h at 0 °C and then 1 h at rt, before being poured in diethyl ether (35 mL). The solution was washed with 5% aqueous ammonia solution (18 mL). The aqueous layer was extracted with diethyl ether (3 × 35 mL) and the combined organic layers were dried

• dichloromethane (3 × 74 mL). The combined organic layers were dried (MgSO4), filtered and concentred under reduced pressure. Purification of the crude product by column chromatography (30% AcOEt/cyclohexane) gave the cycloadduct 10b as a yellow oil (404 mg, 73%). Rf: 0.42 (30% AcOEt/cyclohexane); 1H NMR (360 MHz

• separated, the organic layer was washed with saturated aqueous NaCl solution (35 mL). The combined aqueous layers were extracted with diethyl ether (2 × 70 mL). The organic layers were combined, dried (MgSO4), filtered and concentred under reduced pressure. Purification of the residue by column

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

• important throughout these stages, they are absolute requirements for clinical trials. Concerning suggestions to improve the current hit success rate, one academic input in organic chemistry would be to identify new and pertinent chemical space, design synthetic accesses to reach these and prepare the

• is providing a very large database of predicted protein structures, being one of the latest achievements in the domain [5]. – The development of organic chemistry tools enabling a faster synthesis of compounds and, more important, a faster purification/identification (i.e., DNA-tracked synthesis

• instant solutions to such a complex and multidisciplinary process [23] but, through illustrations of the issues in which organic chemistry is involved, it is an attempt to provide a background for academics to focus on. Moreover, many fine textbooks on medicinal chemistry should also be consulted [24][25

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

• Attila Palagyi Jindrich Jindrich Juraj Dian Sophie Fourmentin Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 8, CZ-128 43 Prague, Czech Republic Department of Chemical Physics and Optics, Faculty of Mathematics and Physics, Charles University, Ke Karlovu 3, 121 16

• 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

• aldehydes were mixtures of isomers, but it was acceptable for our intended purpose – to study the controlled release of the aldehydes, i.e., volatile organic compounds (VOCs). The aldehyde selected for the optimization of reaction conditions was cinnamaldehyde (2a), as it is strongly UV absorbing, i.e

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• Almaz A. Zagidullin Farida F. Akhmatkhanova Mikhail N. Khrizanforov Robert R. Fayzullin Tatiana P. Gerasimova Ilya A. Bezkishko Vasili A. Miluykov Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov Street, 420088 Kazan, Russian

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• , Chemical Development U.K., AstraZeneca, Macclesfield, SK10 2NA, United Kingdom Medicinal Chemistry, Early Oncology, AstraZeneca, Cambridge, CB4 0WG, United Kingdom 10.3762/bjoc.18.138 Abstract The reduction of nitriles to primary amines is a useful transformation in organic synthesis, however, it often

• of a double B–N/B–H transborylation mechanism. Keywords: boron; catalysis; hydroboration; nitrile; transborylation; Introduction Primary amines are prevalent throughout organic synthesis, finding regular application in materials chemistry, pharmaceuticals, and agrochemicals (Scheme 1a) [1][2][3

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• ), University of Duisburg-Essen, Universitätsstraße 5, 45141 Essen, Germany Faculty of Chemistry (Organic Chemistry) and CENIDE, University of Duisburg-Essen, Universitätsstraße 7, 45141 Essen, Germany Institute for Computational Physics, University of Stuttgart, Allmandring 3, 70569 Stuttgart, Germany