1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• rapid build-up of target molecules (see Scheme 1a) [7]. Once the important skeletal carbon–carbon bonds have been formed around the thioketal carbon, the sulfur-heterocycle can perform its primary function as a temporary protecting group and be chemoselectively hydrolyzed to afford a carbonyl functional

Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• ]. Saponins, because of their amphiphilic nature, are known as natural surfactants [9]. They have been used as natural detergents, foaming agents, stabilizers, emulsifiers and wetting agents, for example [10]. The micelles produced will be different in size and shape as a function of the type of saponin

• show the sorption isotherms at low solute concentrations. The c-LBG 20Pow matrix sorption behaviour was fitted following the Hill function, but this model does not represent well the absorption process in the low concentration region. For c-XG and c-CS, a wider 1-N concentration range where saponins

• simple hydrogel scaffold for the sorption of 1-naphthol. An aqueous sorbate mixture of five phenolic compounds has been also tested to assess the differences in the sorption behaviours of the different matrices. The absorbed amount changes as a function of the cyclodextrin/polysaccharide ratio, and the

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• ethers and N-heteroarenes by using a novel catalytic system based on sodium iodide (NaI) and triphenylphosphine (PPh3), suggested to function as an electron donor–acceptor (EDA) complex [55][56][57][58][59][60]. Compared to previously reported radical reactions, this novel catalytic system has the key

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• libraries. But how big should this chemical space be, so as to actually address our needs? A general consensus has emerged, supporting that “it is not actually the library size but rather the library diversity in terms of molecular structure and function which is fundamental for a successful drug discovery

• further oxidized, and thus producing the respective benzylic cation. Intramolecular cyclization in the cationic position under participation of the methyl ester function provided the core for (+)-grandilodine C (191) and (+)-lapidilectine B (192), while allylation of the benzylic position allowed

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• deprotonation of 2-(α’-methoxy-γ-pyrone)-1,3-dithiane. The resulting vinylogous enolate intermediate was trapped with the electrophile 3, amounting to the one-pot preparation of compound 4, having a masked carbonyl function connecting both key fragments [27][28]. Isolated and characterized by Schmitz [17], the

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• sequences that are conserved across different types of enzymes and that have a specific function) are used to identify RiPP BGCs beyond family borders as they are present in the BGCs of approximately 50% of all RiPP families [35]. BGCs without conserved signature sequences are almost impossible to identify

• gene annotations representing the different genomes are aligned to compare the genomes not on a sequence level, but instead on the gene-function level [86]. Whole genome alignments are performed to detect single diverging gene loci that are subsequently expanded by their genomic neighborhood to detect

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

• -, and 7-deazapurine mutations of RNA have been fundamental to shed light on their structure, catalysis, and function [13][14][15]. However, difficulties in these fields arise from the lack of efficient synthetic protocols for various deaza-nucleosides and nucleobases. This is particularly true for the

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

• ) acids (Figure 1) have demonstrated various antiviral activities, such as by HIV protease inhibition (IC50 = 8 and 9 μM) [22]. In addition, compound 1 has demonstrated some anti-SARS-CoV activity (EC50 = 10 μM; SI = >10) by having an inhibitory effect on the 3CL protease function [21][23]. Moreover

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

• Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China University of Chinese Academy of Sciences, Beijing 100049, China Dipartimento di Chimica e Biologia “A. Zambelli”, Università di Salerno, I-84084 Fisciano

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

• analyze the function of TadA, we introduced tadA into the quadruple auxotrophic host Aspergillus oryzae NSAR1 (niaD−, sC−, ∆argB, adeA−) (Supporting Information 1, Tables S1 and S2) [26], which has been widely used for biosynthesis of fungi-derived natural products due to its genetic tractability [27

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

• both fragments for the synthesis of an advanced intermediate. The synthetic strategy for the synthesis of the central fragment takes advantage of the proximity between the terminal amino function and the hydroxy function at C9. It was anticipated that both functions could arise from the cleavage of a N

• have therefore completed a quick, efficient and selective access to the central core of leustroducsins/phoslactomycins using an asymmetric nitroso Diels–Alder reaction. This fragment displays a ketone function that will be used for coupling with the lactone fragment 3 by generation of the tertiary

• coupling revealed the incompatibility of the lactone function; therefore, it was reduced with DIBAL-H then transformed into 19 by a one pot acetalization–desilylation procedure (91:9 mixture of diastereomers) [17]. Hydrozirconation followed by treatment with iodine furnished the target vinyl iodide 20

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• unknown; b) previously disclosed C6–Me and C6–amido structure-to-function tools for GMD; c) C6-modified GDP-Mans of type 8 and 9, targeted in this work. Structure of 16 with ADPs rendered at the 50% probability level. Acetyl group disorder is omitted for clarity. Atom colour scheme: carbon = black, oxygen

• = red, phosphorus = purple, chlorine = green, hydrogen = pink. C6–Cl is the gg rotamer (from the Cl6–C6–C5–O5 torsion angle). GMD function with probe 19 over 120 min (GMD (100 µg/mL), GDP sugars (50 µM), NAD+ (200 µM)). Dotted trace dictates expected fluorescence output following spiking with GDP-Man 1

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

• chances of being identified in the course of screenings. In 2004, the Molecular Library Initiative sponsored by the NIH also tried to address such issues and provide probes to determine the function and therapeutic potential of all the human genes. Aside from considerations on the selectivity and drug

• for simplified analogues, hopefully retaining the function of the biologically active compound, is very relevant when considering its potential in medicinal chemistry [279][280][281]. Start from leads obtained from previous research A second research direction for chemists is to start from previously

• consider the much less studied novobiocin (62) depicted in Figure 10. This compound is another naturally occurring antibiotic which was isolated in 1955 [311]. It turned out to be the first inhibitor of the bacterial ATP-ase function of gyrases found and it was actually instrumental in the discovery of

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

• – cinnamaldehyde, cyclamen aldehyde, lilial, benzaldehyde, anisaldehyde, vanillin, hexanal, heptanal, citral, and 5-methylfurfural. Subsequently, the rate of release of the volatile compound from selected pro-fragrances, as a function of the environment (solvent, pH), was studied by 1H NMR spectroscopy (for

• influence of adding hygroscopic salts (MgSO4, LiClO4, or Ca(ClO4)2), triethyl orthoformate, or activated molecular sieves to the reaction. These compounds could function as desiccants removing the water formed during the reaction, as well as catalysts; nevertheless, the conversion to the final imine needed

• dissolution of the pro-fragrance, which influenced the equilibrium between dissociation and formation reactions. The integrals of the imine group signal at 8.30 ppm measured at various time intervals were depicted as a function of time for all the samples with pH from 3 to 12.8. Data were fitted by a

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

• is typically applied to identify the global optimum of an objective function, even if there are many local optima [37][38][39]. At the heart of our implementation of the SA method we carried out Markov Chain Monte Carlo (MCMC) simulations of 1 around 14-3-3ζ with the acceptance criterion of

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

• levels of the electroactive species and work function of the electrodes. Injection of electrons and holes creates oxidized and reduced species near the anode and cathode, respectively. These oxidized and reduced species are stabilized by the ions to form a p-i-n junction in the bulk of the emissive layer

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

• ) function as sterol 14α-demethylases in green plants [24][25][98]. These enzymes catalyse oxidation of the C14α methyl group to trigger elimination of formic acid [24][25]. The sister subfamily CYP51H, on the other hand, is only found in monocots. AsCYP51H10 from Avena sativa (oat) is a multifunctional CYP

• our review provides a good starting point for such further studies. Enzyme function of cytochrome P450 monooxygenases (CYPs). A) Typical net reaction of CYPs, resulting in hydroxylation of a substrate. As monooxygenases, CYPs catalyse transfer of only one oxygen atom from molecular oxygen to their

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

• , we analysed a set of well-known PPK enzymes regarding the thermodynamic equilibrium of ATP synthesis and compared the experimental results obtained with theoretical calculations. The theoretical calculations addressed the equilibrium position of the considered reactions as function of the substrate

• between different PPKs [10][15]. First experiments were conducted with the “model PPKs” EcPPK1 and SmPPK2. At 37 °C and pH 8, each enzyme was incubated with either ADP or ATP and polyP as co-substrate; the resulting nucleotide distributions were analysed by HPLC as a function of time (Figure 4). In all

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• quantitative comparison between different sites, the condensed Fukui function based on atomic charges was calculated. We calculated total populations for all nitrogen atoms in the adenine anion in its N and N−1 electron states to obtain the condensed f− descriptor according to the equation for the

• nucleophilicity (for details, see Computational part in Supporting Information File 1). In purines 2–5, the method for charge fitting suggests that the most positive part of the f– function is localized at the N6 atom, which means that this nitrogen is the most nucleophilic site in adenines (except 1 and 6). In

• Fukui function f- (right) for the adenine anion (isovalue = 0.008) calculated with NPA charges. Dependence of N9-isomer product ratio (%), in the reaction between FcCOCl and adenine anions 1–6, on the averaged perpendicular Sterimol parameter B = (B1 + B5)/2 of the C6-substituent (open circles; in the

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• activation [19]. Thereby, C3-triorganosilyl-substituted furfurals could be suitable platforms to develop a two-step modular approach to 3-substituted 2-furyl carbinols, entailing nucleophilic addition to the aldehyde function and oxygen-assisted electrophilic substitution of the C–Si bond (Scheme 1). Results

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• ; Fukui function; global hardness; nucleophilicity index; 2-phosphaindolizines; Introduction In 1988, we developed a simple synthetic method for the synthesis of 1,3-azaphospholo[1,5-a]pyridine derivative (1, R1 = Me, R2 = PhCO) from the reaction of 2-ethyl-1-phenacylpyridinium bromide with PCl3 and Et3N

• reagents [19]. Thus a quantitative descriptor, the Fukui function was defined as for nucleophilic attack and for electrophilic attack, where ρN+1(r), ρN(r), and ρN−1(r) are the electron densities at a point r in the system with N+1, N, and N−1 electrons, respectively, all with the ground-state geometry

• of the N-electron system. It was concluded that the regions of a molecule with a large Fukui function are chemically softer than the regions where the Fukui function is small. Thus, by invoking the HSAB principle it becomes possible to predict the behavior of a particular site in the molecule towards

Mechanochemical bottom-up synthesis of phosphorus-linked, heptazine-based carbon nitrides using sodium phosphide

• Blaine G. Fiss,
• Georgia Douglas,
• Michael Ferguson,
• Jorge Becerra,
• Jesus Valdez,
• Trong-On Do,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2022, 18, 1203–1209, doi:10.3762/bjoc.18.125

• 31P NMR chemical shifts were calculated using the plane-wave density function theory (DFT) code CASTEP v20.11 (see Supporting Information File 1 for full computational details) [45]. In the absence of an experimentally resolved crystal structure for g-h-PCN, we followed a similar methodology to our

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• successfully prepared [32]. The protocol, using NaI as a catalyst and K2S2O8 as an oxidant, tolerated a broad range of substrates with good stereoselectivity. Interestingly, structurally related benzothiazine derivatives with a carboxylic function in the C-3 position are only seldomly described in the

• . Results and Discussion We began our work with the condensation reactions of 2-aminothiophenols 8 and bromopyruvic acid and esters 9 to form 4H-benzo-1,4-thiazines 10, having a carboxylic acid or an ester function at the C-3 position (Scheme 1). The reaction of thiol 8a with bromo-substituted acid 9a in

• our work, we aimed to utilize the carboxylic acid function of the prepared 4H-benzo-1,4-thiazines 10 by attaching them to nonproteinogenic amino acid 16a and ʟ-phenylalanine. Preparation of 3-propylnorleucin methyl ester (16a) started with the condensation reaction of heptan-4-one (12) and methyl

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• responsible for the oxidation of deoxyhangtaimycin (3), a compound with antiviral activity, to 1 [8]. The thereby installed hemiaminal function is also the breaking point for 1 into a larger lactone-polyene peptide fragment and a smaller fragment HTM222 (2, named after its molecular mass of 222 Da) [2

• later revised as that of (Z)-4. The same compound is also observed in S. olivaceus [10] and was reported to function as a competitive inhibitor of glutathione S-transferase [11], which may be a result of a thiol addition of glutathione to the Michael acceptor in 4. While the relative and absolute

• suggests that the natural function of this structurally remarkable compound awaits future clarification. HPLC analyses of (Z)-4 on a chiral stationary phase. A) Nearly racemic 4 from the first synthetic route (Scheme 2), B) enantiomerically enriched 4 (80% ee) from the second synthetic approach (Scheme 3

Enzymes in biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1131–1132, doi:10.3762/bjoc.18.116

• assembly line logic, with individual domains for each single step [2]. Furthermore, the domains are organized into modules, each of which is responsible for the incorporation of one extender unit into the growing polyketide or peptide chain. With our knowledge today, the function of these large enzyme