Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

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

• arylpyrrole antimalarial series [82]. We are not aware of a similar real-time, fully open source effort being applied to anthelmintic discovery, but this would be an exciting prospect for the field. However, researchers have been freely releasing open tools useful for drug discovery, openly describing their

• to radically open up the drug development process, with the goal of increasing the efficiency, reducing the cost of research duplication, reducing the hoarding of data and creating collaborative communities [174]. This approach has been applied to the discovery of compounds with antimalarial activity

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• , such as monitoring of specific biological activities and as antimalarial and anticancer agents [5][6]. However, electroactive properties of derivatives of this acceptor have been scarcely reported. Quinazoline-based compounds were used as hosts for red phosphorescent OLEDs with an external quantum

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• group publication [74] on new antimalarial drugs can be highlighted (Scheme 29). The authors report a 3.4 gram-scale preparation of ascaridole, in this case a synthetic intermediate, using TPP as photocatalyst. Another example of a scaled-up endoperoxide approach involves the stereoselective singlet

• -flow with O2). One very relevant example of a photooxygenation protocol is the Seeberger group’s semi-synthesis of the antimalarial API artemisinin (Scheme 32) [79]. They have established a gram-scale continuous protocol with a photooxygenation promoted by TPP starting from dihydroartemisinic acid

• oxygen and their mechanisms. Adapted from [67]. First scaled up ascaridole preparation from α-terpinene. Antimalarial drug synthesis using an endoperoxidation approach. Photooxygenation of colchicine. Synthesis of (−)-pinocarvone from abundant (+)-α-pinene. Seeberger’s semi-synthesis of artemisinin

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• dihydroartemisinic acid (DHAA) [64][65]. Also, high efficient and recyclable catalytic systems based on metal-organic frameworks (MOFs) have also been reported for the tandem hemisynthesis of artemisinin [66]. In a remarkable work, this antimalarial drug was obtained by a new route involving enyne metathesis as the

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

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

• (i.e., entombment) makes the ARC in result tables more difficult to extract. A specific example of the problem can be given for a 2017 article on new antimalarial compounds entering development [8]. Because the chemistry representations were restricted only to images in the PDF a blog post was

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• possess nonselective activities in biological systems and exhibit antimicrobial [28], cytotoxic [29], antimycobacterial [30], and antimalarial [31] effects. Pigmentosin A (1) and its new derivative pigmentosin B (2) exhibited weak activity against B. subtilis, with MIC values of 12.5 and 100 μg/mL

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

• restricted members possess significant biological activities, like the anticancer agent taxol (1) [4] or the antimalarial agent artemisinin (2, Figure 1) [5][6]. The structural diversity and functional utility of this class of specialized metabolites have combined to encourage efforts to apply the tools of

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

• variety of pharmacological and antimicrobial properties [5][6], including analgesic, antihypertensive, anti-inflammatory, anticancer, antifungal and antimalarial activity (Figure 1). A key feature of the tetrazole ring is its bioisosteric character with the carboxylic acid and amide functional groups

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• [1][2][3]. Sesqui- and diterpenes are a diverse class of secondary metabolites derived predominantly from plants, marine invertebrates, fungi and some prokaryotes [4][5][6][7][8]. Properties of these natural products include antitumor, anti-oxidant, anti-inflammatory, antiviral, antimalarial

• inexpensive carbon sources. Prominent examples of optimized terpene production pathways in E. coli are taxadiene, a precursor of the anticancer drug taxol [28], amorpha‐4,11‐diene, an antimalarial drug precursor [29], and cyclooctatin [30]. The scope of this review encompasses a detailed consideration of the

Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• engineering; terpenes; Introduction Amorphadiene synthase (ADS) from Artemisia annua is a key enzyme involved in the biosynthesis of the antimalarial sesquiterpene drug artemisinin (1) [1][2][3][4]. ADS catalyses the Mg2+-dependent conversion of farnesyl diphosphate (FDP, 2) to amorpha-4,11-diene (3) with

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

• length of the extended pentafulvene chain, and the role of the fulvene in the reaction (diene or dienophile) [127]. In these examples, kigelinol and neoamphilectane are of great interest in biomimetic and natural product chemistry, as they exhibit antitrypanosomal [128][129] and antimalarial [130

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• . Immunobiological properties of compound 1 SLs, natural compounds predominantly isolated from the species Asteraceae and Apiaceae represent a rich source of small molecules with potential pharmacological effects. Indeed, some of them have reached clinical applications as antimalarial (artemisinin; [24]) or

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

• 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

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

• , that shows antimalarial activity [40] and satavaptan, a selective V2-receptor antagonist that is useful for the treatment of cirrhosis (Figure 5) [41][42]. Additionally, methisazone is a 2-oxindole derivative that has been used as antiviral drug, especially for the prophylactic treatment of small-pox

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• -hydroxymethyl-9-epi-artemisinin (18), starting from the known and readily available chiral aldehyde 3 and alkyne 4. Subsequently, the synthesized compounds have been evaluated for their antimalarial activity against the drug-sensitive P. falciparum NF54 strain. All of them were inactive. In addition, they did

• of artemisinin (1; qinghaosu, Figure 1) from Artemisia annua L. and the discovery of its antimalarial properties in 1971 represent one of the greatest medical breakthroughs of the 20th century [1][2]. For these achievements Youyou Tu was awarded the Nobel Prize in Physiology or Medicine in 2015 [3

• , whereas the desired (+)-3-hydroxymethylartemisinin (2) was produced from 17 in two steps including epimerization and cleavage of the TES group in excellent yield (Scheme 3). Finally, we evaluated the antimalarial activity of (+)-3-hydroxymethylartemisinin (2) as well as of the derivatives 16 and 18

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• -product generated during the synthesis of the antimalarial chloroquine [2]. Given this high potential for the discovery of useful chemical entities, we have recently been engaged in research regarding a family of quinolone natural products which are produced by the actinomycete Pseudonocardia sp. CL38489

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• nicotinamides to highly functionalised quinolines, such as the antimalarial drug quinine. The ability of this protocol to tolerate such highly functionalised molecules, with such a variety of functional groups present, really justifies the claims of the authors that this protocol is ideal for LSF in drug

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• ]. The reaction was rationalized by participation of the C-3 neighboring group (structure 104) with intermediate formation of a dioxolanium derivative 105 [23]. On the other hand, the Mitsunobu reaction was advantageous for the acetalization of the antimalarial drug dihydroartemisinin 106 to give 107

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• . Suckling et al. designed a set of 31 Strathclyde minor groove binders (S-MGBs), derived from distamycin, by varying the head groups (amidine, amide, or alkene), heterocyclic building blocks and their alkyl substituents and the basicity of the C-terminal tail group in order to investigate their antimalarial

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• synthesis of the antimalarial drug hydroxychloroquine (HCQ). Key improvements in the new process include the elimination of protecting groups with an overall yield improvement of 52% over the current commercial process. The continuous process employs a combination of packed bed reactors with continuous

• stirred tank reactors for the direct conversion of the starting materials to the product. This high-yielding, multigram-scale continuous synthesis provides an opportunity to achieve increase global access to hydroxychloroquine for treatment of malaria. Keywords: antimalarial; API manufacturing; flow

• of the malaria parasite Plasmodium falciparum. Hydroxychloroquine (1) is an antimalarial drug developed for both treatment and prevention of the disease in response to the widespread malaria resistance to chloroquine (2, Figure 1) [5][6]. Additionally, hydroxychloroquine (1, HCQ) is an effective non

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -arylaminopyrazolo[1,5-a]pyrimidines 143 by the coupling reaction of 7-chloropyrazolo[1,5-a]pyrimidines 140 with various aryl amines 141 in ethanol, which were evaluated for their anti-Plasmodium falciparum, antimalarial, and Pf-dihydroorotate dehydrogenase inhibitory activity (Scheme 40). 7-Arylaminopyrazolo[1,5-a

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• , it was essential to have a phenyl as a substituent in order to get good yields. A radical mechanism was proposed but the role of oxygen was not discussed. Aminoquinoline derivatives are found in naturally occurring and synthetic bioactive compounds, most notable for their antimalarial activity. So

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• regioselectively form this instead of 3a and 4. This tricyclic backbone can be found in compounds that possess a wide range of medicinal properties including those with antimalarial [74], anticancer [75][76], antiallergic [77][78], antibacterial [79], and antimicrobial properties [80][81]. In addition, they have

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• applications in biology and medicine to mimic the phosphate group leading to antiretroviral drugs (e.g., tenofovir (1)) [39], isoprenoid biosynthesis inhibitors [40][41], antibiotics (e.g., fosfomycin (2)) [42], tyrosine phosphatase inhibitors 3 [43], antimalarial 4 [44], antihypertensive drugs (e.g., K4 5 and