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

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

• and scalable reaction conditions. Here, we report a continuous-flow approach to metallaphotoredox catalysis using a heterogeneous catalyst that combines the function of a photo- and a nickel catalyst in a single material. The catalyst is embedded in a packed-bed reactor to combine reaction and

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• . Interestingly, we found that CYP158C1 clusters together with a T3PKS gene in the S. cattleya genome, which is similar to the biflaviolin [30] and naringenin [31] biosynthetic gene clusters. The native function of these type-III polyketide synthase products is believed to be involved in the protection of 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

• in organic synthesis and sometimes appear in biologically active compounds, pharmaceuticals, agrochemicals and functional molecules, amidomethylation induced by N-acyliminium ions is a helpful and valuable protocol for direct introduction of an amide function into organic molecules. Generation of N

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• the two-component flavin-dependent monooxygenase Ady3/Ady10, as in the valanimycin biosynthesis mediated by VlmH/VlmR [15][16][17]. The hydroxylamine would be conjugated to alanyl-tRNA to form an ester intermediate by the function of the tRNA-utilizing enzyme Ady7, which is homologous to VlmA. In

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• has the same function as EchA, which only catalyzes the Claisen–Dieckmann condensation of phenylpyruvic acid (7) to generate polyporic acid (8) [26]. Based on the gene knockout and biochemical characterization experiments, we proposed a possible biosynthetic pathway for daturamycins in S. sp. KIB

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

• /trans mixture), the potential of the recycled BMImBF4 to function as a N-heterocyclic carbene precursor was demonstrated. Interestingly, the reaction selectivity is completely lost using the recovered IL, and experiments are undergoing in order to understand the cause of this selectivity loss. Batch vs

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• characterized the function of a P450 enzyme CYP76AH1 which was responsible for the formation of the aromatic ring of ferruginol in the biosynthesis pathway of tanshinones [34]. Hence, we proposed that the oxidation occurred on L to furnish the aromatic ring of calamenene (M) [29], followed by the hydroxylation

• aristolane cyclization. The ubiquitous co-existence of enantiomeric cadinane-type sesquiterpenoids in the sponge revealed the unique catalytic properties of sponge-derived terpene synthases, which attracts our attention for further investigation of their structure–function relationship. Further elucidation