Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• N1,N5-substituted biguanides, that shows little variation in reactivity. By adapting these conditions, other reactants can be used such as nitrogen-containing heterocycles, other aminated nucleophiles, or ortho-substituted anilines, extending the scope of this reaction to a broader diversity of

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• glycoconjugates [1][2][3][4]. Due to the large diversity of glycosyl donors and acceptors there is no general glycosylation method developed so far. To ensure high yielding, as well as regio- and stereoselective glycosidic bond formation, a proper combination of glycosyl donor and acceptor, protecting and leaving

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• provided an easy access to the synthesis of complex bioactive molecules with multiple point diversity incorporating up to eight components in one-pot [8]. The pharmaceutical industry has witnessed a considerable surge in drug synthesis via multicomponent strategies [9][10][11], including the synthesis of

• capacity and modes to achieve the uphill task easily [19]. The contemporary organic chemistry procedure involving microwave heating has paved way for the molecular diversity that helps in reducing the time required for the drug discovery process. As multicomponent reactions and microwave reactions hold

• of MWA-MCR in the construction of fused polycycles with functional diversity for the generation of a library of pharmacologically active molecules. The construction of fused annulated rings are seldomly reported often achieved by a sequential addition approach [40]. Contributing to the same and

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

• derivatives, including electron-donating or electron-withdrawing substituent groups in the para- or meta positions at the benzene rings, giving corresponding products in moderate yield. This protocol is also suitable for the structural diversity of epoxides, providing a new activation approach for C(sp3)–H

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• containing an isoxazole moiety is of key interest in this study since previously our group reported [19] a successful usage of 3-aminoizoxazoles as unusual amine components in the Ugi-4CR reaction and here we continue to build molecular diversity of isoxazole-derived Ugi products and their successors

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• Discussion Synthesis of starting compounds for enzymatic hydroxylation In order to estimate the possible diversity of the substrates as starting materials for the biocatalytic transformation, cortisol (1) was converted to a hydroxylated steroid derivative 2 by reduction of the C20 carbonyl group with NaBH4

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• synthetic methods, the multicomponent Mannich-type condensation strategy shows a high efficiency, convergent feature, and product diversity. It can be expected that the convergent multicomponent condensation synthetic strategy will show wide applications in the preparation of biologically active

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

• diversity of complications that could hinder protein studies with fluoroprolines. On the other hand, in the presence of R-Flp, the folded and fully active PWA enzyme was isolated, clearly demonstrating the ability of this analog to abolish the ribosome stalling issues in vivo. This is in full agreement with

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity

• Dmitrii A. Shabalin,
• Evgeniya E. Ivanova,
• Igor A. Ushakov,
• Elena Yu. Schmidt and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29

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

• -Difluorocyclopropanes easily undergo various transformations leading to the formation of a diversity of useful materials. Although gem-difluorocyclopropanes contain a strained ring, they are kinetically stable under the conditions employed for many synthetically important reactions. These include the catalytic

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• : DMSO-d6, 90 °C. Single-crystal X-ray analysis of diethyl (9-heptyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-9H-purin-6-yl)phosphonate (4d). CCDC-2044976. Structural diversity and synthetic methods of purinylphosphonates. MWI = microwave irradiation; LG = leaving group. Synthetic routes for the formation of

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

• introduce a significant amount of steric and electronic diversity from the C-3 amide vector, we switched the amide coupling agent from TBTU to the more reactive HATU [8][9]. To our surprise, the amide coupling step furnished almost quantitatively the C2–OAt ether 15 [10] and only traces of the expected C2

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

• of functional photocatalytic systems [16][17]. The diversity of crown ether-based photocatalytic reactions is relatively low, involving mainly photocycloaddition reactions. Saltiel and co-workers reported the regiospecific intermolecular [2 + 2]-photocycloaddition based on a supramolecular assembly

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• because the methods normally neglect self-interactions. The advantages of homooligomeric complexes over monomer proteins include an increase in the diversity of the functions [61], allosteric regulation [62], protection against denaturation [63], and the oligomers being able to form without increasing the

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• diversity, these compounds constitute a motif in various natural alkaloid products, such as chimanine and those derived from lobelia, sedum, etc. These compounds act as anti-HIV and anti-asthma drugs [9][10][11]. Mainly, 2-substituted quinolines and their analogues exhibits magnificent bioactivity [12][13

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• ][32][33][34][35][36][37] and in accordance with the polarized Nazarov reaction concept developed by Frontier [27][33]. In an effort to broaden the scope of the reaction and the diversity of products, we assumed that the N-heterocycles 5, bearing the propargyl side chain at C3, would deliver a

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

• complex, reflecting the high structural diversity of peptide and glycan portions. The use of glycopeptide-centered glycoproteomics by mass spectrometry is rapidly evolving in many research areas, leading to a demand in reliable data analysis tools. In recent years, several bioinformatic tools were

Secondary metabolites of Bacillus subtilis impact the assembly of soil-derived semisynthetic bacterial communities

• Heiko T. Kiesewalter,
• Carlos N. Lozano-Andrade,
• Mikael L. Strube and
• Ákos T. Kovács

Beilstein J. Org. Chem. 2020, 16, 2983–2998, doi:10.3762/bjoc.16.248

• significant impact on bacterial communities since bacterial soil communities have a higher diversity in dry than in rainy seasons [14]. Besides the seasonal factors, even different plant species with varying root exudates as well as various soil types impact the microbial community composition in the

• , Bacillus amyloliquefaciens (now identified as Bacillus velezensis), and Bacillus cereus to the roots of broccoli plants led to species-dependent changes in the diversity, evenness, and relative abundances of endophytic bacterial communities [32]. Like many other soil bacteria, B. subtilis and other

• demonstrated that the production of these NRPs varies among coisolated B. subtilis environmental strains due to missing core genes or potentially altered gene regulation, highlighting the existing natural diversity of SM production in this species [51]. In this study, we focus on soil-derived semisynthetic

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• and (ii) permits to synthesize pyrroles with a high potential of molecular diversity and complexity. However, to date, the productivity for creating molecular diversity and complexity has yet to be fully displayed. In addition, some of the reported approaches were established on the basis of using

• , and thus enriching the product diversity of the pyrrole derivatives. Representative biologically active N-(hetero)aryl-4,5-unsubstituted pyrrole scaffolds. Typical routes to N-(heteroaryl)-4,5-unsubstituted pyrroles. Substrate scope of the pyrrole synthesis. Synthesis of N-heterocyclic pyrroles

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• show excellent nucleophilicity arising from the oxindole–hydroxyindole tautomerization [18][19], this synthetic approach is undoubtedly attractive because it could complement our previous one using nucleophilic amido-functionalized allyl boronates in terms of the structural diversity as well as

• an amide side chain [14]. Therefore, we here examined reactions using N-alkyl derivatives in order to gain the structural diversity. Reactions of 3-(phenylthio)isoindolinone derivatives bearing an N-benzyl (2c), N-methyl (2d), and N-(n-pentyl) group (2d) with 1a readily proceeded under the optimized

• or N-Boc protection/desulfinative lactonization. The increase of diversity of structure accessible led to further understanding of the structure–cytotoxicity relationship of spirolactams on P388 cells. Syntheses of 3b–o via electrophilic amide allylation of γ-phenylthio lactams. Reactions were

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• -enantiomers with a ratio of 73:27, 4 is the pure (S)-enantiomer, and 5 is the (S)-enantiomer with 98% ee. The present study illustrates the diversity in the stereochemistry of anteiso branching in bacterial metabolites. Compounds 1−4 were moderately antimicrobial against Gram-positive bacteria and fungi, with

• MIC ranges of 6.25–25 μg/mL. Keywords: 1JC,H; alkanoylimidazoles; anteiso; Kocuria; nocarimidazole; Introduction The phylum Actinobacteria contains bacterial genera most prolific as producers of novel natural products with high structural diversity, unique modes of action, and potent bioactivities

• alkanoylimidazoles, nocarimidazoles C (1) and D (2), along with the identification of three known related compounds, nocarimidazoles A (3) and B (4) as well as bulbimidazole A (5). We also discuss the stereochemical diversity of the anteisoalkanoyl group in these compounds. Results and Discussion Strain T35-5 was

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

• Linear Code adaptations to represent reaction rules, we have seen increasing diversity in the syntax, including branch constraints, duplicate monosaccharides omission, logical operators, etc. Here we critically review reaction rule nomenclature. In doing so, we seek to promote the development of a

Particle size effect in the mechanically assisted synthesis of β-cyclodextrin mesitylene sulfonate

• Stéphane Menuel,
• Sébastien Saitzek,
• Eric Monflier and
• Frédéric Hapiot

Beilstein J. Org. Chem. 2020, 16, 2598–2606, doi:10.3762/bjoc.16.211

• out in the presence of KOH as a base. The data series were confronted with kinetics models to get insight in the way the reactions proceeded. The diversity of possible models suggests that multiple mechanochemical processes can account for the formation of β-CDMts in the solid state. Throughout the

• purification steps. We especially focused our attention on the utilization of cyclodextrins (CDs), which are cyclic α-ᴅ-glucopyranoside-based saccharides. CDs feature the advantage of adjustable cavity sizes and a broad synthetic diversity. The most commonly used CDs are α-CD, β-CD, and γ-CD, that consist of 6

• , Figure S1). The presence of KOH did not significantly change the results (Supporting Information File 1, Figure S2). The diversity of cases was even more pronounced for α than for the conversions. Nevertheless, once we calculated the α values, we tried to fit the data series to kinetics models

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• in the crystal structures, which enable a greater diversity of non-covalent interactions with the protein and even different binding modes on the same lysine side chain. With increasing ring size, the calixarenes promote ligand-induced ordered multimerization of proteins. Cyt c for example is

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• building and beyond Carbohydrates present various challenges to the development of force fields [23]. The tertiary structures of monosaccharides usually have a high number of chiral centres which increases the structural diversity and complexity. The structural diversity changes the electrostatic landscape