One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• ; Introduction Tetrazole is a privileged heterocycle existing in a range of biological and medicinally interesting compounds [1][2] with antifungal [3][4], antibacterial [5], anticancer [6][7], antiparasitic [8], and antihypertensive properties [9] including FDA approved drugs such as valsartan and cefmetazole

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• the IMP dehydrogenase involved in inosinic acid metabolism [2]; ascofuranone (Figure 1, 2), which exhibits antiparasitic activity by selectively inhibiting the oxidase of Plasmodium trypanosoma [3]; and pyripyropene (Figure 1, 3), which displays hyperlipidemia treatment activity through the inhibition

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• activity) [16], ramariolide A (antitubercular) [17], (+)-massarinolin A (antibacterial) [18], anemonin (antiparasitic) [19], (+)-pyrenolide D (cytotoxic) [20], and (+)-crassalactone D (antitumor) [21]. Synthetic or semisynthetic spiro Δα,β-butenolides have also shown a range of biological properties

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• their ability to produce antiparasitic activity against neglected tropical parasites such as trypanosomes and leishmanias is largely underinvestigated. Therefore, we studied the biological activity profile of compound 1 against Trypanosoma brucei subsp. brucei strain GUTat 3.1 and Leishmania donovani

• (Laveran and Mesnil) Ross (D10). Compound 1 showed promising antiparasitic activity against Leishmania donovani with IC50 of 4.85 µM compared to the laboratory standard amphotericin B with IC50 value of 4.87 µM (Table 2 and Figure S13 in Supporting Information File 1). When tested against Trypanosoma

• DMSO-d6, HRESIMSMS sequence tagging data with GNPS molecular networking and the advanced Marfey’s test. We proposed that the biosynthesis of compound 1 is similar to that of other surfactin-like lipopeptides previously reported in the literature. We found compound 1 to possess remarkable antiparasitic

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• sequences of the model actinomycete Streptomyces coelicolor A3(2) [1] and the producer of the antiparasitic drug avermectin, Streptomyces avermitilis [2], were published. These index cases marked the transition from the pre- to the post-genomic era in microbial natural product (NP) research [3]. The

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• synthesis of various natural and synthetic products. MBH adducts itself display diverse biological activities like antifungal, antibacterial, herbicide, antiparasitic and antitumor as reviewed by Lima-Junior et al. (2012) [45]. It was envisaged that in comparison to the traditional methods like Pictet

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• to 4 µM (Table 1). Thus, the antiparasitic activity of persubstituted pyrazoles is about two orders of magnitude lower compared to the antimalarial amodiaquine (EC50 = 6 nM). Also many other antimalarials such as chloroquine, quinine, mefloquine, and artesunate, tested in the SYBR Green or comparable

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

• donors have shown important biological activities due to their unique electronic and coordination ability [37][38], such as antitumor [39] and antiparasitic [40][41]. Previously, furoxans were synthesized via dimerization of hydroximoyl chlorides in the presence of a base, such as trimethylamine in ether

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• antiparasitic study of brevipolides C, G, H, and J (3, 7, 8, and 10) and the IC50 (mM) data obtained are summarized in Table 3 [5]. These compounds demonstrated varying activity levels against multiple Leishmania strains, Trypanosoma cruzy, Plasmodium falciparum, and Giardia lamblia (Table 3, entries 1–8

• ). Except for G. lamblia, brevipolide H (8) showed the best antiparasitic activity against all the tested human intestine parasites with IC50 values of 12.5–50.4 mM. Thus, this compound has great potential as a lead structure in parasite research. A cytotoxicity study of these four compounds against HeLa

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• captivated synthetic chemists and biologists alike since the 1960s due to their efficient DNA binding, antitumour and antiparasitic activities [1]. Such compounds include the DNA and RNA-fluorescent marker ethidium bromide (1), the cell viability probe propidium iodide (2) and the naturally occurring

• antiparasitic compounds, trisphaeridine (3), decarine (4) and nortidiene (5) (Figure 1). The importance of the phenanthridine framework has inspired the development of numerous synthetic strategies to access these compounds. These include the classical Pictet and Ankersmit pyrolysis of N-benzylideneaniline [2

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• and synthetic chemistry. Compounds of this class have shown important activities, such as anticancer and antiparasitic, besides the commercially available drugs. These properties led to the development of efficient and greener synthetic methods to achieve the 2H-chromen-2-one core. In this context

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

• historical examples illustrate the strength of open science in the C. elegans research tradition. In the following sections of this review we discuss how open science approaches continue to be important in the field of anthelmintic and antiparasitic drug discovery. Open approaches to target identification

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• compounds with biological activities ranging from antitumor, antiviral, antibiotic and antiparasitic to cannabinoid receptor modulating [22][23][24][25][26][27][28]. Despite the attractive features of the quinolone-3-carboxylate scaffold, there are only four reported routes towards this valuable structural

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• biological activities including antiparasitic (albendazole, mebendazole), antiulcer (omeprazole), antihypertensive (candesartan, telmisartan, azilsartan, medoxomil, mebefradil), anticancer (bendamustine), antiemetic/antipsychotic (droperidole), antihistaminic (astemizole, emedastine) and many others (Figure

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

• sesquiterpene lactone is still unknown [5]. Whereas artemisinins are almost non-toxic to normal cells, several studies have confirmed their potent antitumor activity [6][7]. In addition, they have been reported to possess immunosuppressive, anti-inflammatory, antiviral, antifungal and antiparasitic activities

Gold-catalyzed post-Ugi alkyne hydroarylation for the synthesis of 2-quinolones

• Xiaochen Du,
• Jianjun Huang,
• Anton A. Nechaev,
• Ruwei Yao,
• Jing Gong,
• Erik V. Van der Eycken,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2018, 14, 2572–2579, doi:10.3762/bjoc.14.234

• derivatives, 2-quinolone and 4-quinolone, are the core structural elements of many natural products and pharmaceutical agents [1][2][3]. In particular, 2-quinolone derivatives show a broad range of biological activities including antiviral [4][5][6][7], antimicrobial [8][9], antiparasitic [10][11], anti

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• antimicrobial [3] and antifungal properties [4]. In addition, antiparasitic activity has been studied for some members of this family as inhibitors of trypanothione reductase [5], an essential enzyme of the kinetoplastid Trypanosoma brucei. Their activity as selective T-type calcium channel blockers [6][7][8][9

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• , these analogues may also have antibiotic, antifungal, anticancer, antiparasitic, and immunosuppressive properties. Conclusion This study demonstrated a viable approach to synthesize spinetoram J and its analogues. Compared with the previous semi-synthesis of spinetoram J, the improved semi-synthesis

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• investigated Dec-NH2, its LZ template and single/double substituted derivatives for their ability to selectively kill MCF-7 breast cancer cells. Results and Discussion Peptide design, chemical synthesis, purification and physicochemical analyses Dec-NH2 is a cationic α-helical antimicrobial and antiparasitic

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

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• withdrawal, etc. [26][27][28][29][30][31][32][33][34]. In addition, these azaheterocycles also exhibit anti-inflammatory, antitumor, antiparasitic and anxiolytic activities [35][36][37][38][39][40][41][42]. In particular, 1,4-benzodiazepine derivatives are proposed to serve as a structural mimic of peptide β

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

• Pyrazolo[3,4-b]pyrazines have received great attention because of their interesting biological activities such as inhibition of protein kinases [137], blood platelet aggregation [138], bone metabolism improvers [139] as well as antifungal [140], antibacterial [141], antiparasitic [142] and antiviral [143

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• , antiparasitic, hypnotic, etc. [1][2][3][4][5]. It is recognized as a key scaffold due to its broad occurrence in a number of drug candidates and drugs, such as zolpidem [6] (1a, used in the treatment of insomnia), and alpidem [6] (1b, an anxiolytic agent). Some imidazopyridine derivatives also act as β-amyloid

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• defence mechanisms. This molecule is produced by macrophages and the antimicrobial and antiparasitic properties of NO have been well described [38]. Currently, the role of NO as a mediator between chronic inflammation and carcinogenesis is intensively studied [39]. The expression of inducible NO is under

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• antineoplastic doxorubicin and by the antiparasitic avermectin (Figure 1a) [1]. PK are assembled from acyl-coenzyme A (acyl-CoA) units via a series of Claisen-type condensation reactions catalyzed by polyketide synthases (PKS) (Figure 1b). PKS occur as large multifunctional enzymes, termed megasynthases, which