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

• , apparently [88][89][90][91]. Concerning the definition of drug-like compounds, past the ground breaking Lipinski’s rule of five [92], defining more precise criteria for the inclusion of a given chemical, possibly dependent on the target considered, remains an interesting research subject [88][93][94][95][96

• for their synthesis were often due to preceding hit to lead research programs followed by their inclusion in chemical libraries. But there was also the more academic stance “we can reach these compounds with our new chemistry so let’s investigate its scope and prepare some derivatives”. And all this

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

• hydrophilic outer surface and hydrophobic cavity. This cavity can encapsulate another lipophilic guest molecule and thus form an inclusion complex [3][4]. This phenomenon is reversible and leads to an equilibrium between encapsulated and free guest. A staggering number of inclusion complexes of CDs with

• easiest accessibility; besides, β-CD forms usually the strongest inclusion complexes compared to α-CD and γ-CD. The amino-β-CD was prepared according to published procedures [25][26][27]. Common commercially available volatile aldehydes 2a–j (Figure 2) were chosen as the aldehyde reactants. Some of the

• that CD-based pro-fragrances combine a chemical barrier, as the aldehydes are linked to the CD via imine bond, and a physicochemical (supramolecular) barrier, as we established that aldehydes formed inclusion complexes in aqueous solution with β-CD. We confirmed from the NMR kinetic study of the imine

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• carbocation A’ is significant, due to the exchange of two π-bonds for σ-bonds, as well as gain in dispersion interactions on folding of the extended geranylgeranyl cation. Discussion Although the current calculations were performed in the gas phase without inclusion of the enzyme environment, we may still

Introducing a new 7-ring fused diindenone-dithieno[3,2-b:2',3'-d]thiophene unit as a promising component for organic semiconductor materials

• Valentin H. K. Fell,
• Joseph Cameron,
• Alexander L. Kanibolotsky,
• Eman J. Hussien and
• Peter J. Skabara

Beilstein J. Org. Chem. 2022, 18, 944–955, doi:10.3762/bjoc.18.94

• thiophene groups and has been applied in solution processed OFETs. A maximum hole mobility of 1.33 × 10−4 cm2 V−1 s−1 was measured for a single device. The isolation of the dibromide compound 29 provides the basis for the inclusion of this interesting molecule in larger conjugated structures or copolymers

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• successful guest-inclusion, Michael reactions were performed with prism 15 (Figure 4). Generally, most of the organocatalysts get destroyed during the work-up procedure, so that recovery is often difficult. However, in the present case the catalyst could be easily recovered, and multiple catalytic cycles could

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• was commonly introduced through in-situ, noncovalent inclusion/encapsulation in the cavity or by covalent, post-functionalization of the macrocyclic scaffold. The encapsulated catalytic group could occupy the space for substrate entering, or has a risk to be squeezed out of the cavity under complex

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water

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

Beilstein J. Org. Chem. 2022, 18, 429–437, doi:10.3762/bjoc.18.45

• G guest molecule were involved in the inclusion complex and further self-assembled to form worm-like supramolecular nanostructures, which displayed an AIE effect via restricted phenyl-ring rotation of m-TPEWP5. After that, the negative EsY acceptor was loaded on the positively charged surface of the

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• recognition of cholylglycine, which is a combination of cholic acid and glycine. The β-cyclodextrin/graphene oxide composite forms an inclusion complex with a β-NQS guest. The amino group of cholylglycine can bind to β-NQS by a nucleophilic substitution reaction, resulting in a decrease in the electrochemical

Host–guest interaction and properties of cucurbit[8]uril with chloramphenicol

• Lin Zhang,
• Jun Zheng,
• Guangyan Luo,
• Xiaoyue Li,
• Yunqian Zhang,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2021, 17, 2832–2839, doi:10.3762/bjoc.17.194

• Q[8] formed a 1:1 inclusion complex (CPE@Q[8]) with an inclusion constant of 5.474 × 105 L/mol. The intervention of Q[8] did not affect the stability of CPE, but obviously reduced the release rate of CPE in artificial gastric and intestinal juice; Q[8] has a slow-release effect on CPE. The

• in water and has a bitter taste. Upon forming an inclusion complex with cyclodextrin, the solubility and bitter taste of CPE can be improved [4][5]. Ramesh Gannimani et al. [6] reported that the inclusion complex of cyclodextrin and CPE loaded silver nanoparticles possessed stronger antibacterial

• properties than CPE alone. Ana I. Ramos et al. [7] studied the inclusion compound of CPE and cyclodextrin and reported its effect on Enterococcus, Bacillus, Staphylococcus and other bacteria. As a new type of supramolecular host compound, cucurbit[n]urils [8][9][10][11][12][13][14][15][16][17][18][19] (Q[n]s

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• derivative 28, which has a lower tendency for ring expansion. At room temperature, this substrate stopped at the hydrated intermediate 29, which could be isolated and remained intact when heated to 80 °C alone in 1,4-dioxane. Inclusion of the gold catalyst while heating, however, initiated the rearrangement

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• ) functionality [97]. The cryogels were synthesised by photochemical crosslinking of N,N-dimethylacrylamide (DMA) and β-CD triacrylate (Figure 7) and aripiprazole was incorporated through inclusion inside the hydrophobic β-CD domains. The release of aripiprazole was monitored at pH 1.2 and 6.8, targeting oral

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• the center. The modifications chosen for inclusion into this review involve some of the more commonly used amine groups that have been attached as a single modification either on the nucleobase, sugar, or internucleotide linkage. When structurally depicted in this paper, modifications are shown with

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• (acetylacetonate) in the cross-coupling cycle. They achieved the desired cross-coupling products 89 with the reaction conducted in open air and under mild conditions (Scheme 35) [109]. Notably, the use of propylene carbonate as the co-solvent removed the need for inclusion of reductant or oxidant additives, such

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• properties from the charged carboxylate groups within its polyuronic acid backbone. The design and inclusion of isosteric replacements for these carboxylates would underpin provision of new oligo-/polysaccharide materials with alternate physicochemical properties. Presented herein is our synthesis of

• has a similar pKa to a carboxylate yet provides enhanced hydrogen bonding capability and alternative prospects for permeability due to a larger hydrophobic region enabling improved lipophilic contacts. These alternative properties and a prospect for their inclusion within new alginate fragments led us

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

• interconnected output. The potential inclusion of downstream inlets allows for further reagent addition and direct telescoping into a subsequent reactor/reaction step. This can in theory be repeated as many times as is desired. This approach is being increasingly adopted to address synthesis problems across both

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

• bromo derivative 2 and take a closer look at how the halogen influences the conformation of the porphyrin macrocycle. The first thing to note is how planar this structure of 2A is compared to 2 (see Supporting Information File 2, Table S1). Even with the inclusion of nickel(II) in compound 2A most of

• displacement, there are only minor differences seen due to the inclusion of the metal center with compound 18 showing the lowest distortion with a small decrease in the atom displacement (Supporting Information File 2, Table S6). This is further compounded when moving to compound 19 with the large steric

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• involved in TGFβ inhibition [142]. The inclusion of LNA nucleosides within a larger single-stranded DNA oligonucleotide has also allowed for subtle gene modifications to be implemented while evading mismatch repair (MMR) [143]. Furthermore, Ju et al. recently reported the use of LNA-based suppressors for

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

• report the efficacy, delivery capability, and functionality of the addition of peptides and RNA aptamers in facilitating entry through a simplified BBB model as well as to determine whether inclusion of these molecules could facilitate cell specific uptake. We further show that LNPs generally exhibit a

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

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

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

• rim of the CDs could also be optimized, leading to the conformational fixation of both the sensitizer and the guest within the chiral cavity and producing the high ee values. For 8c and 8d, the self-inclusion of the aromatic chromophore might be interrupted, resulting in the long distance from the

• negatively charged CoPyS and EY was suppressed by the inclusion of γ-CD. Calixarene-based photocatalysis CAs are derived from the shape of the chalice. They can be obtained by bridging phenolic units through methylene groups in the meta-position. Their rigid goblet structure has two edges. The wider upper

• cavity and strong bonding ability with various guests, macrocycles function as a tool to promote the specific conversion of substrates. On the one hand, the close inclusion of substrates by macrocycles can realize the intervention in, and regulation of the reaction, and thereby developing a new type of

Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification

• Steffen Lippold,
• Arnoud H. de Ru,
• Jan Nouta,
• Peter A. van Veelen,
• Magnus Palmblad,
• Manfred Wuhrer and
• Noortje de Haan

Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253

• inclusion of closely eluting isomeric and isobaric interferences. Of note, isomeric glycopeptide compositions were summed and not processed individually. This approach makes RT alignment a crucial step for a robust quantification. With the optimized parameters in place, LaCyTools allows highly automated

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• . Interestingly, the fullerene C60 was not taken up as a guest by the tetramer (6)4 in chlorinated solvents. For a more defined self-sorting, the authors switched the solvent from CDCl3 to [d8]-toluene. Now, a 2-fold completive self-sorting delivered the homoleptic inclusion complexes [(5)4(C60)] and [(6)4(C60

• (SelfSORT-II). Such type of transmetalation in metal–NHC complexes with a retention of the individual homomeric supramolecular assemblies has not been reported in literature. Recently, a quantitative and reversible structural interconversion of supramolecular structures was achieved by the inclusion and

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• obtained with DeoxoFluor at elevated temperature (Scheme 2). A side-product in this fluorination reaction was the tricyclic compound 12, which presumably formed through an electrophilic aromatic substitution reaction of the activated alcohol intermediate. The inclusion of TMS-morpholine [29] reduced the

A consensus-based and readable extension of Linear Code for Reaction Rules (LiCoRR)

• Benjamin P. Kellman,
• Yujie Zhang,
• Emma Logomasini,
• Eric Meinhardt,
• Karla P. Godinez-Macias,
• Austin W. T. Chiang,
• James T. Sorrentino,
• Chenguang Liang,
• Bokan Bao,
• Yusen Zhou,
• Sachiko Akase,
• Isami Sogabe,
• Thukaa Kouka,
• Elizabeth A. Winzeler,
• Iain B. H. Wilson,
• Matthew P. Campbell,
• Sriram Neelamegham,
• Frederick J. Krambeck,
• Kiyoko F. Aoki-Kinoshita and
• Nathan E. Lewis

Beilstein J. Org. Chem. 2020, 16, 2645–2662, doi:10.3762/bjoc.16.215

• to a cataloged reaction [38]. The inclusion of an EC number in the reaction rules table, therefore, promotes the clarity, interoperability, and reproducibility of the generated reaction model. A common syntax used by most studies is the leftmost “ ( ” to represent the terminal, non-reducing end of

• utility of Linear Code in glycoinformatics has been extended by the inclusion of new symbols, relations, and attributes that accommodate the challenge of specifying reaction rules. Yet various implementations conflict with each other and the original Linear Code. Here, we have delineated the various