Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• substituents like fluoro on only one indole ring are favorable for CB receptor binding. The pentafluoroethylated DIM derivative 3ad was the best CB1 ligand of the present series with a Ki value of 1.82 µM. The binding curves of 3e and 3ad are depicted in Supporting Information File 1, Figure S1. Compound 3e

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• forms a repeating pattern of face-to-edge interactions with only minimal interference from the axial ligand (Supporting Information File 1, Figure S39A) and a hydrogen-bonded network between the methoxy moieties (Supporting Information File 1, Figure S39B). Both features are expressed throughout the

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• for the construction of C–C bonds in an asymmetric fashion. This review covers known catalytic systems used for this transformation. For clarity, we are using the type of ligand as a sorting criterion. Finally, we attempted to create a flowchart facilitating the selection of a suitable ligand for a

• reaction, however, palladium holds a special place in this area. There are several review articles partially covering this topic [25][26][27][28][29][30][31]. However, a comprehensive review is missing. In the following sections, we attempt to fill this gap. As a sorting criterion, the type of ligand

• the enantioselective β-arylation of cyclic ketones is known [38]. In 2017, Hu et al. presented the possibility of an enantioselective β-arylation of cyclohexanone using the above mentioned ligand L2. Cyclohexanone was in situ oxidized by 2-iodoxybenzoic acid (IBX) to 2-cyclohexenone, that subsequently

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• forms, the effect of thermally induced unfolding of dye-labeled, quadruplex-forming oligonucleotides in the presence of the ligands was studied. In general, the binding of the ligand to the G4-DNA leads to a stabilization and thus to an increasing melting temperature of the DNA (Table 2). This effect of

• ) [49] and insulin (a2) [50], or in telomerase inhibition (F21T) [30][51][52]. At a ligand-DNA ratio (LDR) of 5, the derivatives 5b–e induced a small, but significant shift of the melting temperature of the oligonucleotides F21T (∆Tm = 1.8–3.9 °C), and FmycT (∆Tm = 1.3–2.1 °C), while the melting

• ). However, no isosbestic points were observed during these titrations, which indicated different binding modes at the particular ligand-DNA ratios (LDRs). The resulting binding isotherms obtained from the photometric titrations were employed to determine the binding constants Kb (Table 3, Figure S5

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• trans-THP. Feng and co-workers’ FeCl3-catalyzed Prins cyclization strategy to 4-hydroxy-substituted THP. Selectivity profile of the Prins cyclization under participation of an iron ligand. Sequential reactions involving Prins cyclization. Banerjee and co-workers’ strategy of Prins cyclization from

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• transferrin receptor is highly expressed in brain capillaries, nucleated cells, and in rapidly dividing cells [21], and its endogenous ligand transferrin has previously been used to increase transport of small molecules and oligonucleotides across the BBB [21][22][23]. The peptide T7 consisting of seven amino

• structures, which makes them ideal molecules for novel ligand development [31]. Zhou et al. previously reported on an RNA aptamer specific for the HIV-1 entry coreceptor C-C chemokine receptor type 5 (CCR5) [34] and an RNA aptamer specific for the HIV-1 envelope protein gp160 [35]. The CCR5 RNA aptamer G-3

• of the nature of the target proteins. CCR5, a cell surface receptor, is internalized upon ligand binding before recycling back to the cell surface or processed for degradation in the lysosome [34]. On the other hand, gp120 is a viral surface protein that is involved in viral entry through

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• and Co(OAc)2, did not improve the yield of 2a (Table 1, entries 6 and 7). Product 2a was formed in 21 and 49% yields, respectively when the reaction was conducted in the absence of the transition metal salt and bpy ligand (Table 1, entries 8 and 9). TMSN3 was indispensable in this reaction because the

• catalytic amount of AIBN (Scheme 4, bottom) [51]. Table 1 shows that the C(sp3)–H bromination reaction proceeds in the absence of a transition metal salt or bpy ligand, and was accelerated by transition metal salts, especially Mn(OAc)2. In addition, the results also suggest that TMSN3 is required for the C

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• bidentate diphosphine ligands having a rigid structure and has increased attention as a useful and effective ligand in coordinating with various metals [19][20]. (Z)-Ph2PCH=CHPPh2 is very important as a bidentate ligand for many mononuclear complexes [21][22][23]. On the other hand, (E)-Ph2PCH=CHPPh2 acts

• as a monodentate ligand for mononuclear complexes, but it is highly attractive because a hierarchical structure can be constructed by cross-linking between two metals [24][25][26]. Considering the characteristics of the coordination form between the (E)- and (Z)-isomers, the development of a

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• phase separation. Modified process for the synthesis of pincer ligand 4. Modified process for the synthesis of pincer-type ligand 6. Synthesis of thioamides a. Supporting Information Supporting Information File 72: NMR data for compounds 2–6 and thiophosphonic acid. Funding This work was supported by

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• step without any transition-metal catalyst, ligand, or photocatalyst, this method possesses a splendid application prospect. The reaction mechanism is as follows (Scheme 48): Firstly, carbon disulfide combines with N-methylaniline (134) in the presence of Cs2CO3 to form thiolate 136. Thiolate 136 is

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• illustrated in Scheme 20 [105]. A methanofullerene variety 69 with a pincer ligand containing a disulfidoaryl moiety was synthesized from 3,5-bis(phenylsulfidomethyl)benzaldehyde hydrazone. In the presence of [Pd(CH3CN)4](BF4)2, the latter gives the corresponding palladium complex 70 (Scheme 21) [106]. A

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• mediated by commercially available Ru homogeneous catalysts [148]. The process afforded C16 to C44 mixtures of macrocyclic oligobutadienes with up to 98% selectivity at moderate conversions (59–88%) using first-generation Ru complexes bearing a tricyclohexylphosphine (PCy3) ligand, mild reaction

• be resistant to the presence of contaminants and impurities (e.g., additives, pigments) [188]. More recently, effective PET depolymerisation was accomplished by a ruthenium molecular catalysts bearing the well-known tripodal phosphorous ligand 1,1,1-tri(diphenylphosphinomethyl)ethane (triphos) [189

• examined, showing the critical operational parameters to be temperature and catalyst concentration, whereas the process was not significantly affected by particle size or stirring speed. Thus, up to 100% Me-La yield was obtained using the six-coordinated Zn(ligand)2 complex sketched in Scheme 9a, either at

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• Xantphos/Pd(OAc)2/t-BuOK and our standard procedure [30][35], in which the amine is added after the lactam 3a, for the initial experiments ended with failure. In most cases, regardless of the used catalytic system (Pd source: Pd(OAc)2, Pd2(dba)3, ligand: DPEPhos, DavePhos, BINAP), solvent (1,4-dioxane

• , toluene) and base (t-BuOK, DIPEA, Cs2CO3), the 1H NMR spectra of the post-reaction mixtures indicated the presence of unchanged substrate 3a. Also, the variation of the reactant quantities (ligand/Pd source = 15:15, 23:15, 23:7.5, 20:20 mol %) and the reaction time did not have a positive effect on the

• the coordination of the amine takes place after the oxidative addition of the organic halide to the palladium–ligand complex. Based on the analysis of our results we have concluded that in the case of systems 3, the order of reagent addition could have a significant impact on a proper course of the

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan 10.3762/bjoc.17.45 Abstract Ligand-targeted microbubbles are focusing interest for molecular imaging and delivery of chemotherapeutics. Lipid–peptide conjugates (lipopeptides) that feature alternating

• serine–glycine (SG)n segments rather than classical poly(oxyethylene) linkers between the lipid polar head and a targeting ligand were proposed for the liposome-mediated, selective delivery of anticancer drugs. Here, we report the synthesis of perfluoroalkylated lipopeptides (F-lipopeptides) bearing two

• ; Introduction Various nano- and microsystems, including micelles, liposomes, and microbubbles, have been developed as imaging agents and to selectively deliver chemotherapeutics to tumor cells [1][2][3][4][5][6]. An increased specificity for tumor cells can be gained through ligand-mediated active targeting

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• exerted by fluoroprolines [108]. As a result, fluoroprolines could significantly impact the transition temperature in elastin-like sequences [108][109]. In ligand-gated ion channels, proline residues are involved in numerous loop positions as well as in the transmembrane helices, and the incorporation of

Mesoionic tetrazolium-5-aminides: Synthesis, molecular and crystal structures, UV–vis spectra, and DFT calculations

• Vladislav A. Budevich,
• Sergei V. Voitekhovich,
• Alexander V. Zuraev,
• Vadim E. Matulis,
• Vitaly E. Matulis,
• Alexander S. Lyakhov,
• Ludmila S. Ivashkevich and
• Oleg A. Ivashkevich

Beilstein J. Org. Chem. 2021, 17, 385–395, doi:10.3762/bjoc.17.34

• -containing alkylation reagents [27]. Very recently, this aminide was found to be a suitable ligand for manganese complexes [28] and used as the agent for the preparation of salts with high energy density [29]. Also, it is worth noting that today only a few examples of mesoionic tetrazole aminide X-ray

• -aminide ligand in a manganese complex [29], being the only structurally characterized complex with a neutral 1,3-dialkyltetrazolium-5-aminide. Therefore, it is of interest to compare the structural data for this compound with those obtained for compound 8a to find the influence of the complexation on the

• ligand structure. As can be seen, the bond lengths of the free 1,3-di-tert-butyltetrazolium-5-aminide 8a and the ligand in the manganese complex are rather close. Nevertheless, the following structural differences attract attention. In the complex, the endocyclic N1–C5 and N4–C5 bonds are shorter, but

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• fluorinated probes and their incorporation into macromolecules, the application of 19F NMR to monitor protein–protein interactions, protein–ligand interactions, physiologically relevant ions and in the structural analysis of proteins and nucleic acids. The continued relevance of the technique to investigate

• proteins. It has also become a widely adopted method for ligand screening, enabling the evaluation of small molecule–protein interactions over a wide range of affinities. In protein-observed fluorine NMR experiments (PrOF) binding events can be readily monitored using simple 1D techniques, and the

• dissociation binding constant of ligands (Kd) determined from the changes in the chemical shift of the labelled nuclei within the protein. Intuitively, the largest chemical shift perturbations are expected to be seen for residues in the closest proximity to the bound ligand. An additional advantage of this

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• activity. An effective method for the synthesis of sterically hindered o-quinones containing 1,3-diketonate, dinitrile and p-quinone-methide functional groups at the periphery of the ligand has been developed. The novel compounds have rigid and conjugated structures and exhibit properties typical of o

• ligand; 1,3-dithiole; ditopic ligand; o-quinone; thiete; Introduction There are a number of methods which may be used for the synthesis of new o-quinones in order to vary their redox properties and coordination abilities. The key features of o-quinones are redox activity as well as chelating

• coordination ability. The redox state of o-quinone (semiquinone or catechol) could be changed both as free species or when it is coordinated to a metal ion as a ligand. Thus, the redox isomerism phenomenon was reported for o-quinone complexes with both transition and non-transition metals [1][2][3]. The

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• a 73% yield. The Suzuki coupling of boronate 6a and aryl bromide 9a using palladium acetate and cesium carbonate in the presence of the ligand SPhos [25] yielded biaryl 10a with virtually quantitative yield (98%, Scheme 4). Unfortunately, the removal of non-identified byproducts and of 9a (which had

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• binding properties [25] and reactions with bovine serum albumin [27]. Cyclam is known as a tetraamino-macrocyclic ligand, which binds strongly to give complexes with many transition metal cations. While catalytic applications of square planar cyclam complexes are reported for metals, such as Ni [30][31

• showed no interaction with Au(III), as expected. A similar resistance to coordinate was observed for the open diamides 1c–e. The phosphorus containing ligand 1c did undergo phosphorus oxidation instead of Au(III) coordination. No effect was obtained by refluxing or by adding additives, such as silver

• ) coordination [43][45][46], Likewise, Δδ1Hcoord 0.3–0.5 ppm for all the neighboring N–CH and N–CH2 protons indicated ligand tetra-coordination to Au(III), as well. Upon coordination of ligand 5a, four different 15N NMR values for the nitrogens were observed. This might be explained by the nitrogens becoming non

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• considers the interaction at multiple binding sites, which might be identical or non-identical. Thus, the model is generally applicable for any possible scenario with more than one ligand. In addition to the enthalpy, the titration curve contains direct information of the stoichiometries and equilibrium

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• . Finally, we turned out attention to transition metal-catalyzed formation of phenols from aryl halides [5]. After another round of screening, we successfully applied palladium-catalyzed conditions discovered by the Buchwald group [6], using KOH as the nucleophile and X-Phos as the ligand, to afford 7 in 83

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• that the catalyst efficiency is almost constant even after five cycles, but the rate of the reaction considerably decreased from the first cycle (0.31 min−1) to the fifth cycle (0.15 min−1). Zhang, Lu, et al. prepared β-CD-decorated CdS nanocrystals (CdS–CD, Figure 9) via a ligand-exchange reaction

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• ] promotes the binding of ligands exhibiting a high local negative charge density, such as sulfotyrosinated P-selectin glycoprotein ligand-1 (PSGL-1) [23] or heparin [24]. A versatile synthetic ligand that takes advantage of binding to cationic target sites, is dendritic polyglycerol sulfate [25] (dPGS), due

• achieved. As specific biological interactions strongly rely on the receptor–ligand interplays, we are interested in investigating the targeting of isolated receptors by supramolecular polymers built from peptide amphiphiles decorated with suitable ligand structures. The well-known L-selectin described