Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• protecting-group-free synthesis [13], are gradually drawing more and more the interest of organic chemists as a sustainable way to deliver structurally diverse chemical libraries for biological screening. The current review is focusing on selected examples utilizing a radical-based divergent total synthesis

• chemical libraries with natural scaffolds for biological screening. The evidenced increase of divergent radical syntheses in the last few years indicates that this approach is here to change the way chemists will practice total synthesis in the future. Evolution of radical chemistry for organic synthesis

• the latter, which is proven in the number of steps and the overall yield, hence establishing it as highly appealing for further development (Scheme 1). In order to identify the new pharmaceutical leads of tomorrow, drug discovery relies on the available chemical space rising from existing chemical

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

• corresponding chemical libraries. Concerning hit to lead programs on a given target, if no new hits are available, previously reported leads along with new structural data can be pertinent starting points to design, prepare and assay original analogues. In conclusion, this text is an actual plea illustrating

• chemistry culture caused by this lack of academic support. Indeed, virtual docking has yet to demonstrate that it was instrumental in preselecting a really successful hit out of chemical libraries and considering, for instance, anticancer drugs as potential antivirals is barely more relevant than assaying

• miniaturization to undertake fast screening campaigns of very large chemical libraries using targets and/or phenotypic-based assays. – The development of structural sciences providing very precise ideas on the kinetic, thermodynamic or on the mode of interactions of chemicals with their biochemical targets. Which

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• to develop efficient, high-yielding, and green routes to isoxazoles are always highly desirable. New approaches to 3,4,5-trisubstituted isoxazoles, particularly to the ones that leverage diverse chemical libraries, are exciting due to a limited number of suitable methods. One current route is the

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• generation of DNA-encoded chemical libraries. Results and Discussion The synthetic strategy for the synthesis of novel functionalized 1,2-oxazole derivatives is outlined in Scheme 1. The synthetic sequence began with preparing β-keto esters 2a–h by treating N-Boc-protected cyclic amino acids 1a–h with

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• not new to research. The pioneer multicomponent reactions are the Hantzsch (1882), Biginelli (1891), Mannich (1912), Passerini (1921), and Ugi (1959) reactions [3]. The significance of such a phenomenal approach for the synthesis of novel compounds first began as a way of increasing the chemical

• libraries and then shifted to obtaining products that are in high demand on an industrial scale at a cheaper and more benign way [4]. Recently, negative human impacts have been greatly witnessed as a result of population growth, so environmentally friendly design has become one of the most important

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• [42][43][44][45][46]. In our research endeavors, we have been involved in the exploration of the synthetic potential of 1-formyl-9H-β-carboline (an alkaloid, kumujian C) [47] for preparing chemical libraries of β-carboline-substituted [48][49][50][51][52][53][54] and N-fused heterocycles [55][56

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• approach. The polyfunctional molecular scaffolds were tested on the cyclopentenone reactivity to further expand the skeletal diversity, demonstrating the utility of this combined approach in generating novel spiro compounds as starting material for the generation of chemical libraries. The chemoinformatics

• characterization of the newly-synthesized molecules gave evidence about structural and physicochemical properties with respect to a set of blockbuster drugs, and showed that such scaffolds are drug-like but more spherical and three-dimensional in character than the drugs. Keywords: chemical libraries

• molecular scaffolds to develop chemical libraries can increase the chance of finding compounds able to address the so-called “undruggable” targets, such as protein–protein interactions [1]. In this context, molecules containing one or more rings are of primary interest, as they will suffer a reduced

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• peptidomimetics with potential pharmaceutical applications. Therefore, the development of innovative Ugi reactions is crucial for the synthesis of novel chemical libraries for various purposes [12]. In recent years, one of the modifications for Ugi reactions is the introduction of bifunctional substrates into the

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

• fluorescence polarization assay of 50,400 compounds from the Chemical Diversity, Maybridge and Chembridge chemical libraries, and subsequent dose-dependent evaluation of the disruption of the SSB/ExoI complex, led to the discovery of four inhibitors, CFAM, BCBP, BOTP and MPTA (24–27, Figure 6), with IC50

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• artificial building blocks with various functions are available, expanding chemical libraries of peptides and oligonucleotides significantly [8][9][10][11][12][13][14][15]. Furthermore, thus designed and synthesized peptides and oligonucleotides can be conjugated with each other to integrate their

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• conditions are mild and selective and the reactions proceed rapidly with generally good yields. Application of this tunable strategy towards the rapid constitution of chemical libraries of biologically active molecules is now actively pursued in our laboratory. Experimental General procedure A: dibromination

Synthesis of enones, pyrazolines and pyrrolines with gem-difluoroalkyl side chains

• Assaad Nasr El Dine,
• Ali Khalaf,
• Danielle Grée,
• Olivier Tasseau,
• Fares Fares,
• Nada Jaber,
• Philippe Lesot,
• Ali Hachem and
• René Grée

Beilstein J. Org. Chem. 2013, 9, 1943–1948, doi:10.3762/bjoc.9.230

• successfully developed for these sequential reactions. By carrying out various types of Pd-catalyzed coupling reactions for compounds with a p-bromophenyl substituent a route to focused chemical libraries was demonstrated. Keywords: 19F/1H HOESY; gem-difluoroalkyl derivatives; organo-fluorine compounds

• representative 5-membered heterocyclic systems with CF2R side chains by using cyclocondensation reactions. Furthermore, selected molecules in these series were functionalized by using appropriate palladium-catalyzed coupling reactions en route to chemical libraries. Results and Discussion The first example of a

• possibility of using these molecules as scaffolds for the preparation of focused chemical libraries. In order to explore this possibility we developed representative examples of Pd-catalyzed reactions starting from p-bromo derivatives 4e and 6e. The results are given in Scheme 7 for pyrazoline 4e. Suzuki

Hydrophobic analogues of rhodamine B and rhodamine 101: potent fluorescent probes of mitochondria in living C. elegans

• Laurie F. Mottram,
• Safiyyah Forbes,
• Brian D. Ackley and
• Blake R. Peterson

Beilstein J. Org. Chem. 2012, 8, 2156–2165, doi:10.3762/bjoc.8.243

• unbleached. Chemical probes also have a variety of half-lives in vivo, a property that may be beneficial in some assays compared to long-lived fluorescent markers, such as mitoGFP and related proteins. High-content screening of chemical libraries against C. elegans treated with HRB 9 and HR101 10 may

Exploring chemical diversity via a modular reaction pairing strategy

• Joanna K. Loh,
• Sun Young Yoon,
• Thiwanka B. Samarakoon,
• Alan Rolfe,
• Patrick Porubsky,
• Benjamin Neuenswander,
• Gerald H. Lushington and
• Paul R. Hanson

Beilstein J. Org. Chem. 2012, 8, 1293–1302, doi:10.3762/bjoc.8.147

• . Computational analyses were employed to explore and evaluate the chemical diversity of the library. Keywords: benzoxathiazocine 1,1-dioxides; chemical diversity; informatics; nucleophilic aromatic substitution (SNAr); sultams; Introduction The demand for functionally diverse chemical libraries has emerged, as

• hindered these efforts [2][3]. In this regard, recent advances in the construction of chemical libraries that are rich in functional diversity, consisting of appendage, functional group, stereochemical and skeletal diversity, have addressed this challenge and also offer new opportunities [4]. Sultams

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• followed by enolization and hydrolysis of the thioester yield orsellinic acid (path B). Inspired by this simple yet universal biosynthetic strategy, which generates structural variation among natural products, we envisioned the construction of chemical libraries featuring modular assembly for the rapid