Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• -hydroxypyrrolidines certainly makes the 4-hydroxyisoxazolidines important and valuable structural fragments in drug discovery. Keywords: 2,3-dihydroisoxazoles; diastereoselectivity; heterocycles; hydroboration–oxidation; isoxazolidin-4-ols; Introduction 2,3-Dihydroisoxazoles (often referred to as 4-isoxazolines

• -trans relative configuration. The resemblance between 3-hydroxypyrrolidines 1 and 4-hydroxyisoxazolidines 2 (Figure 1) makes the latter valuable structural fragments in drug discovery [13][14][15][16][17][18]. Up to now, this class of compounds was commonly prepared using intramolecular nucleophilic

• valuable structural fragments in drug discovery due to their resemblance with 3-hydroxypyrrolidines. Experimental Typical procedure for the hydroboration of 2,3-dihydroisoxazoles (±)-2-Benzyl-3-phenylisoxazolidin-4-ol (8a): A round-bottom flask was charged with the 2,3-dihydroisoxazole 5a (590 mg, 2.49

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• collaboration and the sharing of data and resources between organisations. In this review we discuss how open science has been applied to anthelmintic drug discovery. Open resources, including genomic information from many parasites, are enabling the identification of targets for new antiparasitic agents

• been much progress in creating more potent and selective derivatives. This work exemplifies how open science approaches can catalyse drug discovery against neglected diseases. Keywords: anthelmintic; antiparasitic; cestode; nematode; trematode; Review The need for anthelmintic drug discovery

• the platyhelminths include trematodes (also known as flukes) e.g. Schistosoma mansoni and cestodes (also known as tapeworms), e.g., Taenia solium. Although the current review focusses on the unmet need in anthelmintic drug discovery to tackle the burden of human helminth infections, infection of

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• The synthesis of organoselenium compounds and their biological activity have attracted considerable attention in research fields directed to drug discovery [1][2][3][4][5][6][7][8][9][10][11][12][13]. Among these compounds, heteroaryl selenides and heteroaryl diselenides have been synthesized by a

Pd-catalyzed asymmetric Suzuki–Miyaura coupling reactions for the synthesis of chiral biaryl compounds with a large steric substituent at the 2-position

• Yongsu Li,
• Bendu Pan,
• Xuefeng He,
• Wang Xia,
• Yaqi Zhang,
• Hao Liang,
• Chitreddy V. Subba Reddy,
• Rihui Cao and
• Liqin Qiu

Beilstein J. Org. Chem. 2020, 16, 966–973, doi:10.3762/bjoc.16.85

• Yongsu Li Bendu Pan Xuefeng He Wang Xia Yaqi Zhang Hao Liang Chitreddy V. Subba Reddy Rihui Cao Liqin Qiu School of Chemistry, Guangdong Key Lab of Chiral Molecules and Drug Discovery, Sun Yat-sen University, No. 135 Xingangxi Road, Guangzhou 510275, People’s Republic of China 10.3762/bjoc.16.85

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• ] are common partners in a variety of important cross-coupling reactions. They are also especially valuable precursors to other functional groups such as organic halides, alcohols [5][6][7], etc. Moreover, recent drug discovery efforts have shifted towards the incorporation of these non-natural

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• . However, we will need to await the technical applicability in respect to DARCP capture to see if this opens up connectivity. Keywords: activity data; databases; drug discovery; chemical structures; protein targets; Introduction This article assesses a key aspect of data sharing that has the potential to

• distillation. This report will outline the principles of connectivity capture, selected sources, progress, impediments and prospects for their amelioration. Review Defining terms It is necessary to outline the topics covered: Medicinal chemistry: As directed towards drug discovery this needs no introduction

• . However, in the broader context of bioactive chemistry, it becomes indivisible from the related domains of chemical biology (directed towards mechanistic insight rather that direct drug discovery), enzymology, pharmacology, and toxicology in addition to the development of insecticides or herbicides

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• DNA-photocleavers, and are proposed as new leads for “on demand” biotechnological applications in drug discovery and medicine. Keywords: DNA binding; DNA photocleavage; N–O homolysis; oxime carbamates; photocleavage agents; Introduction Small organic molecules able to bind DNA provide promises for

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

• ; chemoinformatics; Cu-catalysis; cycloadditions; molecular scaffolds; multicomponent reactions; Introduction The screening of small molecule libraries is a well-established approach in early-stage drug discovery to identify hit candidates for the development of drug leads. The application of unconventional

• in numerous natural products [7][8][9], a wide array of spirocyclic compounds are being studied in drug discovery and their chemical space have been systematically charted and characterized recently by Bajorath and co-workers (Figure 1) [10]. This study revealed that spirocycles are found only in few

• respect to 3 and 24, respectively). This feature is promising in view of expanding the array of molecular scaffolds of this nature for drug discovery purpose, as a higher scaffold complexity is generally associated with a more successful outcome in drug discovery and development [69][70][71]. On the other

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• as building blocks in drug discovery, and as ligands in metal-catalyzed reactions [11][12][13][14][15][16]. Their six-membered homologues (5,6-dihydro-4H-1,3-thiazines) are also compounds of broad interest [17], due to their bioactivities [18][19] and as valuable synthetic intermediates [20][21][22

Facile regiodivergent synthesis of spiro pyrrole-substituted pseudothiohydantoins and thiohydantoins via reaction of [e]-fused 1H-pyrrole-2,3-diones with thiourea

• Aleksandr I. Kobelev,
• Nikita A. Tretyakov,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Michael Rubin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 2864–2871, doi:10.3762/bjoc.15.280

• rearrangement (PTR, Scheme 1) [8][9][10][11], which is a special case of a quite poorly investigated iminothiolactone–thiolactam rearrangement [12][13][14][15][16]. This reaction offers attractive opportunities for the design of libraries of regioisomeric hydantoin-based compounds for drug discovery. Spiro

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• Nicky J. Willis Elliott D. Bayle George Papageorgiou David Steadman Benjamin N. Atkinson William Mahy Paul V. Fish Alzheimer’s Research UK UCL Drug Discovery Institute, The Cruciform Building, University College London, Gower Street, London WC1E 6BT, UK The Francis Crick Institute, 1 Midland Road

• biology of Notum and build target validation to underpin new drug discovery programs. Results: An improved, scalable synthesis of 1 is reported. Key modifications include: (1) the introduction of the C7-cyclopropyl group was most effectively achieved with a Suzuki–Miyaura cross-coupling reaction with MIDA

• to 1 which contains functional groups sensitive to certain reagents employed (vide infra). An improved synthetic route should allow 1 to become more readily available as a chemical tool to explore the fundamental biology of Notum and build target validation to underpin new drug discovery programs for

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• prospect of the tetrazole hybridization strategy in drug discovery. Among the most versatile methods for obtaining tetrazoles are the Ugi-azide four-component reaction (Ugi-azide-4CR) [14][15][16] and the 1,3-dipolar cycloaddition of azides with (acyl)cyanides [17][18]. The Ugi-azide-4CR enables the

Perspective isomorphs – a new classification of molecular structures based on artistic and chemical concepts

• Jannis Neumann,
• Ansgar Schnurr and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2019, 15, 2319–2326, doi:10.3762/bjoc.15.224

• collection of molecular models and scientific posters (see Supporting Information File 1). Connection to modeling in drug discovery The classification of compounds by shape has a long tradition in drug discovery [18][19]. With the development in computer technology powerful programs have been developed that

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• play a prominent role as lead structures in drug discovery [1]. Apart from bacteria, fungi are an impressive group of microorganisms in this respect, due to the high structural diversity of their rich secondary metabolism. Fungi are known as producers of many therapeutically important drugs, such as

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

• 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

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

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• Sharpless and co-workers in 2014, for creating molecular connections based on the unique stability–reactivity pattern of the S(VI)–F bond with reliability and efficiency, which has been widely applied in organic synthesis, chemical biology and drug discovery [1][2][3][4][5][6][7][8][9][10][11][12][13][14

• novel sulfonyl fluorides for SuFEx click chemistry with great potential to be applied in the development of covalent inhibitors. Further studies of this class of molecules in chemical biology and drug discovery are underway in our laboratory. Representative sulfonyl fluoride compounds applied in

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• recognition of a far greater taxonomic diversity of microbes that can produce bioactive compounds [1][2][3]. The exploration of previously neglected taxa has been demonstrated to bear significant potential for finding new natural products and is thus highly promising from a drug discovery perspective [4][5

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• biological actions: antiproliferative [6][7][8][9], antimicrobial [10][11], anxiolytic [12], analgesic [13], hypnotic [13], antiviral [13], anti-HIV [13] activities, etc. Soural et al. [14] explored different data and showed the relevance of compounds composed of two or more heterocyclic rings for drug

• discovery. The target products containing a heterocyclic core bound to a peptide-like chain also showed a broad spectrum of biological activity: β-secretase (BACE1) inhibitory activity [15]; inducing apoptosis in colorectal cancer cells [16]; antimalarial activity against a chloroquine (CQ) non-resistant

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• materials for relevant MCRs such as those based on imine and isocyanide. The focus is mainly posed on proving the amenability of MCRs for the diversity-oriented derivatization of naturally occurring steroids and the construction of complex steroid-based platforms for drug discovery, chemical biology and

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• the disruptors of microtubule dynamics, therefore are of great interest in cancer drug discovery [6]. Thereby, the stereocontrolled total synthesis of marine alkaloids such as axinellamines [16] and the search of new 2-aminoimidazole and pyrrole containing compounds with a core structure that mimics

SO₂F₂-mediated transformation of 2'-hydroxyacetophenones to benzo-oxetes

• Revathi Lekkala,
• Ravindar Lekkala,
• Balakrishna Moku,
• K. P. Rakesh and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 976–980, doi:10.3762/bjoc.15.95

• excellent yields. The highlight of this work is the design and synthesis of strained four-membered oxete rings. Keywords: benzo-oxetes; 2'-hydroxyacetophenones; sulfuryl fluoride; Introduction Oxetanes are versatile elements in drug discovery and synthesis [1][2], and represent important moieties in some

• , and less lipophilic molecular units in drug discovery [7][8]. In view of the broad applicability of oxetanes in materials sciences, organic synthesis, and medicinal chemistry [7][8][9][10][11][12][13][14][15], the progress of synthetic routes for the formation of a range of oxetanes is highly

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• Chi-Tung Yeung Wesley Ting Kwok Chan Wai-Sum Lo Ga-Lai Law Wing-Tak Wong The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, PR China State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong

• 1–6.a Supporting Information Supporting Information File 396: Experimental data. Acknowledgements The authors gratefully acknowledge the fundings from the Basic Research Program of Shenzhen (No. JCYJ20160531184120814), State Key Laboratory of Chemical Biology and Drug Discovery, and The Hong Kong

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

• production, and reduced energy consumption [1][2][3][4][5][6][7][8][9]. So, the design of novel MCRs with facile and green processes has fascinated considerable attention in the fields of drug discovery, organic synthesis of natural products, and materials sciences [10]. Undoubtedly, one of the most

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• ; cross-coupling; cyclization; macrocycles; solid-phase synthesis; Introduction Monocyclic and bicyclic peptides are acquiring a relevant interest in current drug discovery. They display improved biological properties over their acyclic counterparts and, at the same time, they are suitable to modulate