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

• , respectively. At this stage, we started to investigate alternative methods to cleave the amide via reduction. Achieving selective C–N-bond cleavage of amides under reductive conditions is still a largely unsolved problem since a C–O-bond cleavage is typically the preferred mode of reactivity, especially when

• using hydride reducing agents [13]. Nevertheless, specialized conditions for achieving C–N-bond cleavage of amides using SmI2 [13], Tf2O/Et3SiH [14], and stoichiometric Schwartz’s reagent [15] have been reported; however, none of these methods was successful in reducing amide 5 to the desired amine 4

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

• synthetic methods, optimizing the reaction process and eliminating the step of intermediate purification to save resources and reduce waste [10][11][12]. The pot, atom, step and economic (PASE) approach [13][14][15][16][17] is one of the most distinguished representatives in the efficient synthesis of

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

• , 162 06 Prague, Czech Republic 10.3762/bjoc.18.170 Abstract A series of β-cyclodextrin dimers selectively permethylated on the primary or secondary rim with two different types of spacers have been synthesized effectively utilizing conventional and newly developed methods. Their structure analyses by

• these methods are also applicable for the methylation of 6-mono-azido derivatives. Compound 1 was used as the starting compound to prepare all dimers with partially methylated rims. It contains one azido group in position 6, and all remaining 6-OH are protected with TBDMS groups; it was prepared

• as the price of some reagents and relatively low yields. In this work, we describe a method using low-cost reactants, such as methyl tosylate and DIPEA, which provides moderate to high yields and is a reasonable alternative to the existing methods. The acetylation of compound 1 using standard

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

• . These methods are so useful because virtually any chemical modification at the deprotected sites can be made followed by global deprotection of the O-benzyl groups with hydrogenolysis. Recently, we observed a strong substituent effect when substituted benzyl groups were used in these reactions with

• cleavage [16] or from 1 by selective protection of the primary OH groups with tert-butyldimethylsilyl groups, followed by benzylation and desilylation [17][18]. We used both methods to prepare 6: The acetolysis method is convenient when perbenzyl α-cyclodextrin (2) is at hand but requires very strict

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• natural products and pharmaceuticals. Valienamine (3) and its analogues show inhibitory activity against certain glycosidases [11][12][13] (Figure 1). Many groups have described different synthetic methods for the synthesis of various aminocyclitols [13][14][15][16][17]. However, only few synthetic

• methods are available for the synthesis of eight-membered [18][19][20][21][22][23][24][25][26][27][28][29] aminocyclitols. On the other hand, the synthesis of a C8-cyclitol derivative containing the aziridine ring has not yet been reported. Therefore, in our continued efforts for efficient syntheses of

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

• -2,3-diones; spirooxindole; Introduction Compounds with a spirooxindole scaffold have attracted the attention of researchers, which is demonstrated by the publication of several reviews of both the biological activities of compounds with the spirooxindole moiety [1][2][3][4][5], and methods for

• and J [16] were also isolated from the fungus Penicillium commune and contain a furan fragment spiro-annulated by 2-oxindole. These compounds exhibit anticancer [13] and antimicrobial [17] activities. One of the expeditious methods for obtaining dihydrofurans is the cycloaddition reaction of diazo

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

• the time. In Table 1, we see a range of different methods based on cross-coupling reactions compared to the method proposed in this work. The first, and one of the most important comparisons, is time. The upper range for our method is in the 5.5 hour mark, whereas most of the literature routes run for

• generally lower yields. This issue could be further minimized upon exploration of recycling the phosphite distillate. It is to be noted that our method, by bypassing the distillation step necessary to remove the solvent in most literature methods, in just 30 minutes on top of the time reported in Table 1

• provides a reaction crude that can be then worked up to obtain the desired product. We also manage to use less catalyst than some of the other methods, except for methods F, G, and H. In keeping with the mild conditions, the temperature we use is 160 °C, which is lower than that of the other reactions

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• ciprofloxacin (Figure 1c). In recent years, the synthesis of quinolines has received great attention and remarkable achievements have been made to produce quinolones by various methods: Skraup reaction [12], Doebner–Miller reaction [13], Combes synthesis method [14], Conrad–Limpach reaction [15], Pfitzinger

• reaction [16], and Friedländer reaction [17]. Among these syntheses, the Friedländer reaction [17] is one of the most commonly used methods for the synthesis of quinolines. However, it has the disadvantages of harsh reaction conditions and low yields owing to the reactivity of o-aminobenzaldehyde when used

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

• , 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

• package. The data were corrected for systematic errors and absorption using the ABSPACK module. The GRAL module was used for analysis of systematic absences and space group determination. Using Olex2 [11], the structure was solved by direct methods with SHELXT [12] and refined by the full-matrix least

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

• detection methods that are dependent on the nature of the stable surface used and the amount of the binding partner that is placed on the surface. If one wants to do a quantitative study of binding events that involve molecules on such a stable surface, then once again a method for calibrating the signal

• can be used to help prevent non-specific binding and minimize biofouling possibilities [18]. While the use of a diblock copolymer coating offers the desired stability advantage, it also rules out the use of both direct methods for conducting synthetic transformations on the array and the direct

• detection methods in the subsequent binding studies. The polymer network is not permeable to molecules tethered to its surface or proteins in solution. The synthetic problem was solved by using the electrodes in an array to generate chemical reagents and catalysts and then confining those reagents and

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

• Arisu Koyanagi Yuki Murata Shiori Hayakawa Mio Matsumura Shuji Yasuike School of Pharmaceutical Sciences, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan 10.3762/bjoc.18.155 Abstract The development of novel and efficient synthesis methods for 2-substituted

• benzazoles containing oxazole and imidazole skeletons are the most commonly used scaffolds [1][2][3][4][5]. Therefore, it is crucial for the drug industry to develop methods for their syntheses [1][2][4][6]. For example, conventional benzoxazole synthesis methods involve the condensation of 2-aminophenol

• conventional methods; a notable alternative is the cyclodesulfurization, where intramolecular cyclization is combined with desulfurization from thioamide analogs such as thioureas, thiosemicarbazides, and dithiocarbamate salts under mild reaction conditions [10]. These synthesis methods are effective for

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• cross-coupling [34] in excellent yield. Esterification of 6 with monomethyl H-phosphonate tert-butylamine salt [35] resulted in the mixed H-phosphonate ester 7 in excellent yield. Cyclization using our homolytic aromatic substitution methodology [36] gave P-heterocycle 8 in modest yield. Other methods

• prepare chiral thiophosphorus acids have been described [41][42][43]. Once equipped with our new methods [38], the synthesis of indole-derived 2 was undertaken (Scheme 3). Known 3-allylindole (10) [44] was obtained from indole uneventfully. Intermediate 11 was furnished in moderate yield via our palladium

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• available, and in fact only few papers describe corresponding synthetic methods [19][20][21][22]. It is well known that labelled compounds (such as those with 2H and 13C labels) can be used as internal standards for the quantitative measurements of the equal compound without label, e.g., straight from the

• methods were used to confirm the formation of the intermediate products 2–4 and the deuterated target compound ApppI(d2). The formation of 2 could easily be confirmed by the presence of carbonyl signal at 178 ppm in the 13C NMR spectrum. Further, the reduction of 2 by LiAlD4 led to the desired compound 3

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

• electron paramagnetic resonance (TREPR) spectra and theoretical methods also support that conformation fluctuations are beneficial to TADF [16]. This is in stark contrast with the SOCT-ISC mechanism. To further explore these contradictory requirements for SOCT-ISC and TADF, we designed herein a series of

• the dyads were studied with steady-state and time-resolved spectroscopic methods, as well as theoretical calculations. Results and Discussion Molecular design and structure confirmation In order to study the effect of conformational flexibility on TADF, NI-PTZ was designed (Scheme 1). As dicussed

• . The synthesis of the dyads is based on the ordinary derivatization of the NI and PTZ chromophores [20]. The molecular structures were confirmed by 1H NMR, 13C NMR, and HRMS methods (Experimental section). UV–vis absorption and fluorescence emission spectra The UV–vis absorption spectra of the

Synthesis of meso-pyrrole-substituted corroles by condensation of 1,9-diformyldipyrromethanes with pyrrole

• Baris Temelli and
• Pinar Kapci

Beilstein J. Org. Chem. 2022, 18, 1403–1409, doi:10.3762/bjoc.18.145

• devices and functional materials, the synthesis of corrole-based analogues has been rather limited due to very few synthetic methods developed to produce corroles with polymerizable substituents at the meso- or beta positions [10][11][12][13]. To date, meso-substituted corroles have been synthesized by

• several methods including; (i) the condensation of pyrrole or dipyrromethanes with aldehydes [14][15][16], (ii) the reaction of 2,2’-bipyrrole with dipyrromethane-1,9-dicarbinols [17][18], (iii) the condensation of bipyrrole-5,5’-dicarbinols with dipyrromethanes [19], (iv) the reaction of dipyrromethane

• -1,9-dicarbinols with pyrrole [20][21], (v) the condensation of dipyrromethane-1-carbinols with dipyrromethanes [22] and (vi) the reaction of tripyrranes with aldehydes [23]. Although many different substituents can be attached to the meso-position of corroles using all these methods, to the best of

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• monitored at 254 nm. Biosynthesis of FC-type diterpenoids. A) The biosynthetic pathway of 1, 2 and 4. B) Cyclization mechanisms of 1 and reported FC-type diterpenes. Supporting Information Supporting Information File 328: Experimental methods, nucleotide sequence, tables, and figures. Acknowledgements We

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

• issue in this regard as a major portion of published data will have to be filtered out before such methods starts to make some tangible headways [57]. For instance, a recent “deep-learning” search for new antibiotics came out with the finding that halicin (1) depicted in Figure 1 was, as many nitro

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

• was next studied by 1H NMR and SH-GC for selected imino-β-CD. The prepared imines could also be mixtures of E/Z isomers, but no attempts were made to isolate them for the reason metioned above. Also, the prepared imines proved to be difficult to purify by chromatographic methods due to their low

• during the NMR studies, no degradation of the cyclodextrin was detected with the available methods. At pH of 11.00, 12.00 and 12.80, a decrease and later (in the case of pH 12.80) a total disappearing of the hydrogen signal of the aldehyde group of benzaldehyde at 10.06 ppm was observed due to

• the system. Sustained release of the aldehyde was demonstrated both in aqueous solutions and from a solid state upon humidity exposure. Experimental Instruments, general methods, and chemicals 1H NMR, 13C NMR, 2D NMR (H,H-COSY, HSQC, and HMBC) were measured on Bruker AVANCE III 600 MHz (600.17 MHz for

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

• (chlorophenyl)ethynes 3b,c to form triarylcyclopropenylium salts 5b,c in 22 and 15% yield (Scheme 2). Unfortunately, it was not possible to synthesize tris(2-chlorophenyl)cyclopropenylium bromide 5a using this method. The structures of 3–5 were confirmed by 1H and 13C NMR as well as IR spectroscopic methods and

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

• ]. Traditionally, the reduction of nitriles to primary amines relied on stoichiometric hydride reagents [4]. Current catalytic methods for nitrile reduction, hydrogenation [5][6] or hydroboration [7][8], generally rely on metal catalysts, designer ligands, forcing reaction conditions (such as elevated temperatures

• hydroboration methods [7]. Author Contributions F. M., A. C. W. K., F. G., A. J. H., K. N., and A. D. B. completed all practical laboratory work. D. R. W. completed all computational analysis. A. D. B., K. N., D. R. W., and S. P. T. conceived the reactions and wrote the manuscript. S. P. T., T. A. H., and T. L

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

• are typically underestimated by orders of magnitude and not accessible to many researchers. A conceivable alternative approach would be the use of docking software such as Autodock Vina [24][25]. However, these docking methods typically have been developed to dock ligands that are not too large and

• not too flexible and ideally have well-defined binding pockets. In contrast, our ligand 1 is large and flexible and does not bind into well-defined pockets but likely is loosely bound to the protein surface by charge–charge interactions. Therefore, standard docking methods are not an option. Since

Ionic multiresonant thermally activated delayed fluorescence emitters for light emitting electrochemical cells

• Merve Karaman,
• Abhishek Kumar Gupta,
• Subeesh Madayanad Suresh,
• Tomas Matulaitis,
• Lorenzo Mardegan,
• Daniel Tordera,
• Henk J. Bolink,
• Sen Wu,
• Stuart Warriner,
• Ifor D. Samuel and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2022, 18, 1311–1321, doi:10.3762/bjoc.18.136

• were prepared from solution and the device was finished with an evaporated Al top contact. Details of the LEEC fabrication can be found in the General Methods section of Supporting Information File 1. Driven by their promising ΦPL LEEC devices using DiKTa-OBuIm and DiKTa-DPA-OBuIm as 1 wt % doped films

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• variety of biochemical, biophysical and computational methods [17][18][19][20][21]. Key for the oxidative chemistry performed by CYPs is a heme prosthetic group that activates molecular oxygen using electrons from an electron donor such as NADPH. A central Fe(III) ion is coordinated by the heme porphyrine

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

• : Details of materials and methods and additional figures and tables. Acknowledgements We would like to thank Katharina Strack for skilful technical assistance, and Dr. Manfred Keller (University of Freiburg) for help with 31P NMR analysis of polyphosphates. Dr. Torsten Sehl (Research Centre Juelich) and