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

• -interlocked catenanes. When both cages were mixed without C70, the dynamic combinatorial library (DCL) of seven compositionally distinct mixed-ligand Zn4L6 cages was observed (Figure 5b). An efficient self-sorting was only observed after the addition of the guest C70. As expected, the cage [Zn4(8')6]8

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• on the endosomal uptake and release. However, a better binding affinity to DNA does not necessarily mean a higher DNA transfection efficiency. As an example, two GCP-modified peptide tweezers 14 with nanomolar dissociation constants, identified by the high-throughput screening of a combinatorial

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• for peptides can be powerful tools for labeling or inhibition. Finding those binding motifs, especially in water which competes for intermolecular H-bonds, poses an enormous challenge. A dynamic combinatorial library can be a powerful method to overcome this issue. We previously reported artificial

• receptors emerging form a dynamic combinatorial library of peptide building blocks. In this study we aimed to broaden this scope towards recognition of small peptides. Employing CXC peptide building blocks, we found that cyclic dimers of oxidized CFC bind to the aromatic peptides FF and YY (K ≈ 229–702 M−1

• ), while AA binds significantly weaker (K ≈ 65–71 M−1). Keywords: artificial receptor; dynamic combinatorial chemistry; dynamic covalent chemistry; molecular recognition; thiolate–disulfide exchange; Introduction Peptides are one of the most abundant and structurally versatile motifs in nature. Thus

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• benign methodologies for the generation of structurally diverse triazinethione derivatives is still challenging in organic synthetic chemistry and medicinal chemistry. Multicomponent reactions (MCRs) gained much interest among synthetic organic chemists as well as in combinatorial chemistry and drug

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• with a bromoalkyne (Scheme 24) [39]. The catalyst was selected using a combinatorial approach for the selection of the optimal catalyst structure. The product was isolated in an excellent 87% yield. In 2018, Wang, Xu, and co-workers described the reductive decarboxylative alkylation of glycine and

• unusual sequence to functionalize molecules. Indeed, it relies on a redox transformation with a concerted proton and electron exchange. Note that this process can occur either through an oxidative or a reductive pathway [47][48][49]. In 2018, during the development of a combinatorial approach to select

• molecule through a transfer of energy to a second one. Then, this second molecule is raised to the excited state and can then react [51][52]. During the course of the design of a library of copper photocatalysts through a combinatorial approach, Collins and co-workers reported the copper-photocatalyzed

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• evolutionary advantage; even more so when combined with tailoring enzymes that have a broad substrate tolerance and catalyze multiple, sequential tailoring reactions [40]. This diversification process resembles the strategy embedded in the construction of combinatorial libraries by organic chemists to generate

• number of bacterial genome sequences available and the development of advanced bioinformatics tools, more type II/I diterpene TC tandems are likely to be discovered. By applying the same combinatorial concept, it is expected that the diterpene chemical space can be significantly expanded. Cytochrome

• step and then modified by tailoring reactions make terpenoid biosynthesis particularly amenable for generating non-natural variants through engineering. It is easy to imagine that the combinatorial pairing of promiscuous TCs and CYPs harbors great potential to achieve this goal, and the integration of

A combinatorial approach to improving the performance of azoarene photoswitches

• Joaquin Calbo,
• Aditya R. Thawani,
• Rosina S. L. Gibson,
• Andrew J. P. White and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2019, 15, 2753–2764, doi:10.3762/bjoc.15.266

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• combinatorial chemistry. This highlight article discusses the unusual properties of fulvenes and their varied cycloaddition chemistry, focussing on applications in organic and natural synthesis, dynamic combinatorial chemistry and materials chemistry, including dynamers, hydrogels and charge transfer complexes

• reactivity and mechanisms of action. Dynamic combinatorial chemistry Dynamic combinatorial chemistry (DCC) is an emerging field with promising applications in drug discovery. DCC involves the generation of new molecules via reversible reactions of simple building blocks, referred to as a dynamic

• combinatorial library (DCL). As the reactions are reversible, several different structures are possible and the system exists in equilibrium. Upon the addition of an external surface (binding target), the equilibrium is altered and the product most stabilised through surface binding is amplified. Under optimal

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• Xiang Sun You-Sheng Cai Yujie Yuan Guangkai Bian Ziling Ye Zixin Deng Tiangang Liu Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, P. R. China 10.3762/bjoc.15.202 Abstract Sesquiterpene

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• been given much attention in various research fields, such as the discovery of lead compounds in medicinal chemistry, or combinatorial chemistry [95][96]. Copper-catalyzed synthetic protocols Ghosh and Mishra [97] have successfully reported the synthesis of imidazo[1,2-a]pyridines in a three-component

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• . We have previously proven the feasibility of this multicomponent approach for the combinatorial synthesis and rapid screening of pseudo-peptide catalysts [7] and their silica gel-immobilized variants [8]. The choice of using acetone and the S-configured α-methylbenzylamine was made in agreement with

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• heterocycles. Especially interesting are the applications of these MCRs [61][62][63][64] in combinatorial chemistry [65] and diversity-oriented synthesis [66], where structurally diverse compound libraries can be rapidly synthesized. Therefore, this article reviews the procedures disclosed recently for the

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• fentanyl contaminating the supply of heroin and cocaine to enhance their overall potencies. This trend is particularly disconcerting due to the observation that the combinatorial consumption of 10% fentanyl in heroin significantly enhances the risk of overdose by prolonging the detrimental effects of

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• of polystyrene resin 3 as the amine component. After resin removal with piperidine in DMF, a combinatorial strategy of replacing the carboxylic acid component with trimethylsilyl azide (TMSN3) (azido-Ugi reaction) or cyanic acid, followed by Fmoc removal (TFA), allowed the formation of the tetrazole

• has been found in the use of dynamic combinatorial chemistry (DCC) [42]. One of the most accessible reversible bonds is the imine bond and has been widely used in DCC. In this context, a freezing process of a dynamic combinatorial library (DCL), which is a system of recognition and thermodynamic

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• supramolecular chemistry are dynamic combinatorial chemistry [11], subcomponent self-assembly approach [12][13][14], and systems chemistry [15][16][17][18], etc. There also has been growing interest towards exploration of nontraditional energy sources like visible light [19][20], microwave [21], mechanochemical

• achieved from benzyl alcohol using a Br+ source as the catalyst (Figure 16). In the reaction pot subcomponents such as benzaldehydes and H+ were formed which further participated in a cascade transformation to give dihydropyrimidones 29. Dynamic combinatorial chemistry and mechano-milling Dynamic

• combinatorial chemistry (DCC) is one of the most important topics which make us understand the relationship between complex molecules and living systems. With this approach, a library of chemical species called dynamic combinatorial library (DCL) can be designed which are in thermodynamic equilibrium with each

Polyaminoazide mixtures for the synthesis of pH-responsive calixarene nanosponges

• Antonella Di Vincenzo,
• Antonio Palumbo Piccionello,
• Alberto Spinella,
• Delia Chillura Martino,
• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2019, 15, 633–641, doi:10.3762/bjoc.15.59

• their relative amount as well. Hence, keeping into account the structures of the precursor species, by means of a simple combinatorial analysis it is possible to show how each component is indeed the product of simple nucleophilic displacement processes. The HR-ESIMS spectra of both mixtures appear very

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• early example involves the synthesis of protease inhibitors by double Ugi 4CR using pyridine-2,6-dicarboxylic acid, isocyanides, amines and aldehydes (Scheme 2), and the combinatorial implications of this protocol were analyzed [6]. Ugi and Dömling soon realized the potential of such experiments, which

• helped to pave the way of combinatorial chemistry and its applications for the fast generation of pharmacological hits through library deconvolution. The reactivity of the system led to complex product mixtures, with no practical substrate selectivity. However, if in analogous experiments several

• formal 8-component adduct can be assembled through a one-pot protocol combining imidazoline, cyanomethylamide and Ugi MCRs. Although the final product is a complex stereoisomeric mixture, the process stands as a milestone for the rapid construction of complex structures, amenable to combinatorial

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• combinatorial library [88]. The work carried out by Davis and co-workers led to the metabolic incorporation of unnatural amino acids (uAAs) bearing a terminal alkene as CM substrates for protein modification [89]. The authors investigated the possibility to incorporate methionine (Met) analogues in a Met

Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents

• Mingjun Yuan,
• Song Lin Chua,
• Yang Liu,
• Daniela I. Drautz-Moses,
• Joey Kuok Hoong Yam,
• Thet Tun Aung,
• Roger W. Beuerman,
• May Margarette Santillan Salido,
• Stephan C. Schuster,
• Choon-Hong Tan,
• Michael Givskov,
• Liang Yang and
• Thomas E. Nielsen

Beilstein J. Org. Chem. 2018, 14, 3059–3069, doi:10.3762/bjoc.14.284

• the PAO1 biofilms, as combinatorial treatment of 2 × MIC of cisplatin with 4 × MIC or 8 × MIC tobramycin killed the biofilm cells at a higher rate compared to the mono-compound treatment (Figure 6). These results suggest that combination of cisplatin and other conventional antimicrobials could be a

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• these established methods necessary. Examples from the past 15 years include transition metal-catalyzed transformations [21][22][23], solid-phase synthesis directed at combinatorial library design [24] and organocatalytic annellation reactions [25][26]. Sparked by our interest in the development and

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• correlated with improved minimal inhibitory concentrations and that Gram-positive microorganisms are more susceptible, likely due to the inability of molecules to permeate the outer membrane of Gram-negative pathogens [88]. In a follow-up study, a combinatorial synthesis approach was utilized to generate a

• a challenge. Thus far, extensive in silico and high throughput screening campaigns of libraries of compounds, combinatorial synthesis and structure-based design approaches, biophysical screening techniques (i.e., fluorescence polarization, surface plasmon resonance and differential scanning

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• synthesis, so they designed second generation inhibitors by changing the synthetically challenging α-Neu5Ac with alpha-hydroxy acids 2 [33][34]. Using a combinatorial approach, a library of non-hydrolyzable, non O-glycosidic third generation inhibitors were synthesised using appropriate linkers. The CTB

• presented on the polymer scaffold with an IC50 value of 0.005 µM. In contrast, the IC50 value shown by a monomeric version of this heterobifunctional ligand 39 was in the millimolar range, similar to the compound m-nitrophenyl galactopyranoside (4). Fulton and co-workers developed a dynamic combinatorial

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Grip on complexity in chemical reaction networks

• Albert S. Y. Wong and
• Wilhelm T. S. Huck

Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147

• ][75][76][77]. The underlying principle of compartmentalization, dynamic combinatorial chemistry, and hydrogelation also appears in different types of networks [78][79][80][81][82][83][84]. Chemical networks can be readily made from tunable organic structures, holding considerable potential in the

• of a bilayer network composed of the mechanical action of a temperature-responsive gel coupled with various exothermic reactions. Reprinted with permission from [34], copyright 2012 Nature Publishing Group. (b) Small dynamic combinatorial library made from dithiol building blocks. Adapted with

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• for the design and discovery of novel technologies, materials, and molecules has its origin in two seemingly unrelated historical figures. Charles Darwin and Josiah Wedgwood Many are not aware that, arguably, one of the first ‘combinatorial’ materials scientists was Josiah Wedgwood. His ultimate

• materials synthesis, characterization, and testing technologies – e.g., RAMP, flow chemistry, high-throughput beam lines, combinatorial chemistry. They suggest that an automatic, closed loop system could be developed where the fittest materials synthesized in a given generation are used to design the next